There are 51 clinical trials

Clinical Trials

1 Epidemiology of Venous Thromboembolism

To evaluate potentially modifiable lifestyle predictors of venous thromboembolism and their joint associations with biochemical and genetic determinants.

NCT00041457 Cardiovascular Diseases Thromboembolism Peripheral Vascular Diseases

MeSH:Thromboembolism Vascular Diseases Peripheral Vascular Diseases Peripheral Arterial Disease Cardiovascular Diseases

HPO:Abnormality of the cardiovascular system Peripheral arterial stenosis Thromboembolism

Archived blood samples were collected from approximately 75 percent of participants at baseline and will be used to assess biochemical and genetic markers of risk including factor V Leiden, the G20210A mutation in the prothrombin gene, hyperhomocysteinemia, and anticardiolipin antibodies. --- G20210A ---

2 Hormone Replacement Therapy and Prothrombotic Variants

To examine in postmenopausal women the potential interactions of hormone replacement therapy with other blood clotting factors on the risk of cardiovascular diseases such as heart attack or stroke.

NCT00049933 Cardiovascular Diseases Heart Diseases Cerebrovascular Accident Myocardial Infarction Hypertension

MeSH:Stroke Heart Diseases Myocardial Infarction Infarction Cardiovascular Diseases

HPO:Abnormality of the cardiovascular system Myocardial infarction Stroke

In an American Heart Association funded case-control study, a potential interaction was observed between HRT and the prothrombin G20210A variant on the risk of first myocardial infarction (MI) in post-menopausal women with hypertension. --- G20210A ---

3 A Study to Assess the Incidence of Deep Vein Thrombosis (DVT) Following Prophylactic Intravenous Administration of Recombinant Human Antithrombin(rhAT) to Hereditary Antithrombin (AT) Deficient Patients in High Risk Situations.

Patients with hereditary antithrombin (AT) deficiency are at increased risk of venous thrombosis and pulmonary embolism, particularly during certain high risk procedures. The trial is focusing on patients with confirmed hereditary antithrombin deficiency who are undergoing a surgical procedure or induced/spontaneous labor and delivery. The study will test the safety and efficacy of recombinant human antithrombin (rhAT) by infusing rhAT prior to, during and following the period of risk or surgical procedure.

NCT00056550 Antithrombin Deficiency, Congenital Biological: Recombinant Human Antithrombin (rhAT)

MeSH:Thrombosis Venous Thrombosis Antithrombin III Deficiency

HPO:Deep venous thrombosis Reduced antithrombin III activity Venous thrombosis

Exclusion Criteria: - Patients who have a diagnosis of hereditary APC resistance, Factor V Leiden, Protein S or C deficiency, prothrombin gene mutation (G20210A), or acquired (lupus anticoagulant) thrombophilic disorder. --- G20210A ---

4 A Phase I Study of Bevacizumab in Refractory Solid Tumors

This phase I trial is studying the side effects and best dose of bevacizumab in treating young patients with refractory solid tumors. Monoclonal antibodies, such as bevacizumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

NCT00085111 Unspecified Childhood Solid Tumor, Protocol Specific Biological: bevacizumab

MeSH:Neoplasms

HPO:Neoplasm

Inclusion Criteria: - Histologically confirmed solid tumor at original diagnosis - Measurable or evaluable* disease - No known curative therapy exists - No lymphomas or primary CNS tumors - No history or clinical evidence of CNS metastasis by head CT scan - Performance status - Karnofsky 50-100% (patients > 10 years of age) - Performance status - Lansky 50-100% (patients ≤ 10 years of age) - At least 8 weeks - Patients without bone marrow involvement: - Absolute neutrophil count ≥ 1,000/mm^3 - Platelet count ≥ 100,000/mm^3 (transfusion independent) - Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed) - Patients with bone marrow metastases: - Platelet count ≥ 75,000/mm^3 (transfusion independent) - Granulocytopenia, anemia, and/or mild thrombocytopenia allowed - No known bleeding diathesis or coagulopathy - No known thrombophilic condition (e.g., protein S, protein C, or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocystinemia, or antiphospholipid antibody syndrome) - PT or PTT ≤ 1.2 times upper limit of normal (ULN) - ALT ≤ 5 times ULN - Bilirubin ≤ 1.5 times ULN - Albumin ≥ 2 g/dL - Creatinine clearance or radioisotope glomerular filtrationrate ≥ 70 mL/min - Creatinine based on age as follows: - Creatinine ≤ 0.8 mg/dL (patients ≤ 5 years of age) - Creatinine ≤ 1.0 mg/dL (patients 6 to 10 years of age) - Creatinine ≤ 1.2 mg/dL (patients 11 to 15 years of age) - Creatinine ≤ 1.5 mg/dL (patients > 15 years of age) - No proteinuria - 24-hour urine protein ≤ 500 mg - No history of stroke - No deep venous or arterial thrombosis within the past 3 months - No uncontrolled hypertension - Hypertension must be well-controlled with stable doses of medication for at least 2 weeks - No history of myocardial infarction - No severe or unstable angina - No transient ischemic attack within the past 6 months - No cerebrovascular accident within the past 6 months - No other arterial thromboembolic event within the past 6 months - No clinically significant or severe peripheral vascular disease - No pulmonary embolism within the past 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for at least 3 months after study participation - No chronic non-healing wound, ulcer, or bone fracture - No significant traumatic injury within the past 28 days - No uncontrolled seizures - No uncontrolled infection - No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies - Recovered from prior immunotherapy - More than 1 week since prior growth factors - At least 2 months since prior stem cell transplantation - No evidence of active graft-vs-host disease - At least 8 weeks since prior monoclonal antibody therapy - At least 7 days since prior antineoplastic biologic agents - No prior bevacizumab - No concurrent prophylactic growth factors - No other concurrent immunotherapy or biologic therapy - More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered - No concurrent chemotherapy - Recovered from prior radiotherapy - At least 4 months since prior craniospinal radiotherapy - At least 4 months since prior radiotherapy to ≥ 50% of the pelvis - At least 6 weeks since other prior substantial bone marrow radiotherapy - At least 2 weeks since prior local palliative small-port radiotherapy - No concurrent radiotherapy - More than 28 days since prior major surgery - At least 7 days since prior minor surgery (for limited purposes of tissue retrieval) and recovered - At least 24 hours since prior placement of an indwelling IV catheter - At least 1 week since prior full-dose anticoagulation therapy, including systemic thrombolytic agents, heparin, low-molecular weight heparin, and warfarin - Local intralumenal anticoagulants (e.g., heparin or tissue plasminogen activator) allowed to maintain patency of preexisting, permanent, indwelling IV catheters or peripheral IV catheters for blood sampling - More than 1 week since prior antipyretic and anti-inflammatory medications (except acetaminophen) - No concurrent full-dose anticoagulation therapy - No concurrent anti-inflammatory medication - Concurrent acetaminophen allowed - No other concurrent cancer therapy - No other concurrent investigational agents Inclusion Criteria: - Histologically confirmed solid tumor at original diagnosis - Measurable or evaluable* disease - No known curative therapy exists - No lymphomas or primary CNS tumors - No history or clinical evidence of CNS metastasis by head CT scan - Performance status - Karnofsky 50-100% (patients > 10 years of age) - Performance status - Lansky 50-100% (patients ≤ 10 years of age) - At least 8 weeks - Patients without bone marrow involvement: - Absolute neutrophil count ≥ 1,000/mm^3 - Platelet count ≥ 100,000/mm^3 (transfusion independent) - Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed) - Patients with bone marrow metastases: - Platelet count ≥ 75,000/mm^3 (transfusion independent) - Granulocytopenia, anemia, and/or mild thrombocytopenia allowed - No known bleeding diathesis or coagulopathy - No known thrombophilic condition (e.g., protein S, protein C, or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocystinemia, or antiphospholipid antibody syndrome) - PT or PTT ≤ 1.2 times upper limit of normal (ULN) - ALT ≤ 5 times ULN - Bilirubin ≤ 1.5 times ULN - Albumin ≥ 2 g/dL - Creatinine clearance or radioisotope glomerular filtrationrate ≥ 70 mL/min - Creatinine based on age as follows: - Creatinine ≤ 0.8 mg/dL (patients ≤ 5 years of age) - Creatinine ≤ 1.0 mg/dL (patients 6 to 10 years of age) - Creatinine ≤ 1.2 mg/dL (patients 11 to 15 years of age) - Creatinine ≤ 1.5 mg/dL (patients > 15 years of age) - No proteinuria - 24-hour urine protein ≤ 500 mg - No history of stroke - No deep venous or arterial thrombosis within the past 3 months - No uncontrolled hypertension - Hypertension must be well-controlled with stable doses of medication for at least 2 weeks - No history of myocardial infarction - No severe or unstable angina - No transient ischemic attack within the past 6 months - No cerebrovascular accident within the past 6 months - No other arterial thromboembolic event within the past 6 months - No clinically significant or severe peripheral vascular disease - No pulmonary embolism within the past 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for at least 3 months after study participation - No chronic non-healing wound, ulcer, or bone fracture - No significant traumatic injury within the past 28 days - No uncontrolled seizures - No uncontrolled infection - No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies - Recovered from prior immunotherapy - More than 1 week since prior growth factors - At least 2 months since prior stem cell transplantation - No evidence of active graft-vs-host disease - At least 8 weeks since prior monoclonal antibody therapy - At least 7 days since prior antineoplastic biologic agents - No prior bevacizumab - No concurrent prophylactic growth factors - No other concurrent immunotherapy or biologic therapy - More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered - No concurrent chemotherapy - Recovered from prior radiotherapy - At least 4 months since prior craniospinal radiotherapy - At least 4 months since prior radiotherapy to ≥ 50% of the pelvis - At least 6 weeks since other prior substantial bone marrow radiotherapy - At least 2 weeks since prior local palliative small-port radiotherapy - No concurrent radiotherapy - More than 28 days since prior major surgery - At least 7 days since prior minor surgery (for limited purposes of tissue retrieval) and recovered - At least 24 hours since prior placement of an indwelling IV catheter - At least 1 week since prior full-dose anticoagulation therapy, including systemic thrombolytic agents, heparin, low-molecular weight heparin, and warfarin - Local intralumenal anticoagulants (e.g., heparin or tissue plasminogen activator) allowed to maintain patency of preexisting, permanent, indwelling IV catheters or peripheral IV catheters for blood sampling - More than 1 week since prior antipyretic and anti-inflammatory medications (except acetaminophen) - No concurrent full-dose anticoagulation therapy - No concurrent anti-inflammatory medication - Concurrent acetaminophen allowed - No other concurrent cancer therapy - No other concurrent investigational agents Unspecified Childhood Solid Tumor, Protocol Specific Neoplasms PRIMARY OBJECTIVES: I. To estimate the maximum tolerable dose (MTD) of bevacizumab by dose escalation to a maximum of 15mg/kg, even if MTD is not reached, administered as an intravenous infusion, every 2 weeks to children with refractory solid tumors. --- G20210A ---

Inclusion Criteria: - Histologically confirmed solid tumor at original diagnosis - Measurable or evaluable* disease - No known curative therapy exists - No lymphomas or primary CNS tumors - No history or clinical evidence of CNS metastasis by head CT scan - Performance status - Karnofsky 50-100% (patients > 10 years of age) - Performance status - Lansky 50-100% (patients ≤ 10 years of age) - At least 8 weeks - Patients without bone marrow involvement: - Absolute neutrophil count ≥ 1,000/mm^3 - Platelet count ≥ 100,000/mm^3 (transfusion independent) - Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed) - Patients with bone marrow metastases: - Platelet count ≥ 75,000/mm^3 (transfusion independent) - Granulocytopenia, anemia, and/or mild thrombocytopenia allowed - No known bleeding diathesis or coagulopathy - No known thrombophilic condition (e.g., protein S, protein C, or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocystinemia, or antiphospholipid antibody syndrome) - PT or PTT ≤ 1.2 times upper limit of normal (ULN) - ALT ≤ 5 times ULN - Bilirubin ≤ 1.5 times ULN - Albumin ≥ 2 g/dL - Creatinine clearance or radioisotope glomerular filtrationrate ≥ 70 mL/min - Creatinine based on age as follows: - Creatinine ≤ 0.8 mg/dL (patients ≤ 5 years of age) - Creatinine ≤ 1.0 mg/dL (patients 6 to 10 years of age) - Creatinine ≤ 1.2 mg/dL (patients 11 to 15 years of age) - Creatinine ≤ 1.5 mg/dL (patients > 15 years of age) - No proteinuria - 24-hour urine protein ≤ 500 mg - No history of stroke - No deep venous or arterial thrombosis within the past 3 months - No uncontrolled hypertension - Hypertension must be well-controlled with stable doses of medication for at least 2 weeks - No history of myocardial infarction - No severe or unstable angina - No transient ischemic attack within the past 6 months - No cerebrovascular accident within the past 6 months - No other arterial thromboembolic event within the past 6 months - No clinically significant or severe peripheral vascular disease - No pulmonary embolism within the past 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for at least 3 months after study participation - No chronic non-healing wound, ulcer, or bone fracture - No significant traumatic injury within the past 28 days - No uncontrolled seizures - No uncontrolled infection - No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies - Recovered from prior immunotherapy - More than 1 week since prior growth factors - At least 2 months since prior stem cell transplantation - No evidence of active graft-vs-host disease - At least 8 weeks since prior monoclonal antibody therapy - At least 7 days since prior antineoplastic biologic agents - No prior bevacizumab - No concurrent prophylactic growth factors - No other concurrent immunotherapy or biologic therapy - More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered - No concurrent chemotherapy - Recovered from prior radiotherapy - At least 4 months since prior craniospinal radiotherapy - At least 4 months since prior radiotherapy to ≥ 50% of the pelvis - At least 6 weeks since other prior substantial bone marrow radiotherapy - At least 2 weeks since prior local palliative small-port radiotherapy - No concurrent radiotherapy - More than 28 days since prior major surgery - At least 7 days since prior minor surgery (for limited purposes of tissue retrieval) and recovered - At least 24 hours since prior placement of an indwelling IV catheter - At least 1 week since prior full-dose anticoagulation therapy, including systemic thrombolytic agents, heparin, low-molecular weight heparin, and warfarin - Local intralumenal anticoagulants (e.g., heparin or tissue plasminogen activator) allowed to maintain patency of preexisting, permanent, indwelling IV catheters or peripheral IV catheters for blood sampling - More than 1 week since prior antipyretic and anti-inflammatory medications (except acetaminophen) - No concurrent full-dose anticoagulation therapy - No concurrent anti-inflammatory medication - Concurrent acetaminophen allowed - No other concurrent cancer therapy - No other concurrent investigational agents Inclusion Criteria: - Histologically confirmed solid tumor at original diagnosis - Measurable or evaluable* disease - No known curative therapy exists - No lymphomas or primary CNS tumors - No history or clinical evidence of CNS metastasis by head CT scan - Performance status - Karnofsky 50-100% (patients > 10 years of age) - Performance status - Lansky 50-100% (patients ≤ 10 years of age) - At least 8 weeks - Patients without bone marrow involvement: - Absolute neutrophil count ≥ 1,000/mm^3 - Platelet count ≥ 100,000/mm^3 (transfusion independent) - Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed) - Patients with bone marrow metastases: - Platelet count ≥ 75,000/mm^3 (transfusion independent) - Granulocytopenia, anemia, and/or mild thrombocytopenia allowed - No known bleeding diathesis or coagulopathy - No known thrombophilic condition (e.g., protein S, protein C, or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocystinemia, or antiphospholipid antibody syndrome) - PT or PTT ≤ 1.2 times upper limit of normal (ULN) - ALT ≤ 5 times ULN - Bilirubin ≤ 1.5 times ULN - Albumin ≥ 2 g/dL - Creatinine clearance or radioisotope glomerular filtrationrate ≥ 70 mL/min - Creatinine based on age as follows: - Creatinine ≤ 0.8 mg/dL (patients ≤ 5 years of age) - Creatinine ≤ 1.0 mg/dL (patients 6 to 10 years of age) - Creatinine ≤ 1.2 mg/dL (patients 11 to 15 years of age) - Creatinine ≤ 1.5 mg/dL (patients > 15 years of age) - No proteinuria - 24-hour urine protein ≤ 500 mg - No history of stroke - No deep venous or arterial thrombosis within the past 3 months - No uncontrolled hypertension - Hypertension must be well-controlled with stable doses of medication for at least 2 weeks - No history of myocardial infarction - No severe or unstable angina - No transient ischemic attack within the past 6 months - No cerebrovascular accident within the past 6 months - No other arterial thromboembolic event within the past 6 months - No clinically significant or severe peripheral vascular disease - No pulmonary embolism within the past 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for at least 3 months after study participation - No chronic non-healing wound, ulcer, or bone fracture - No significant traumatic injury within the past 28 days - No uncontrolled seizures - No uncontrolled infection - No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies - Recovered from prior immunotherapy - More than 1 week since prior growth factors - At least 2 months since prior stem cell transplantation - No evidence of active graft-vs-host disease - At least 8 weeks since prior monoclonal antibody therapy - At least 7 days since prior antineoplastic biologic agents - No prior bevacizumab - No concurrent prophylactic growth factors - No other concurrent immunotherapy or biologic therapy - More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered - No concurrent chemotherapy - Recovered from prior radiotherapy - At least 4 months since prior craniospinal radiotherapy - At least 4 months since prior radiotherapy to ≥ 50% of the pelvis - At least 6 weeks since other prior substantial bone marrow radiotherapy - At least 2 weeks since prior local palliative small-port radiotherapy - No concurrent radiotherapy - More than 28 days since prior major surgery - At least 7 days since prior minor surgery (for limited purposes of tissue retrieval) and recovered - At least 24 hours since prior placement of an indwelling IV catheter - At least 1 week since prior full-dose anticoagulation therapy, including systemic thrombolytic agents, heparin, low-molecular weight heparin, and warfarin - Local intralumenal anticoagulants (e.g., heparin or tissue plasminogen activator) allowed to maintain patency of preexisting, permanent, indwelling IV catheters or peripheral IV catheters for blood sampling - More than 1 week since prior antipyretic and anti-inflammatory medications (except acetaminophen) - No concurrent full-dose anticoagulation therapy - No concurrent anti-inflammatory medication - Concurrent acetaminophen allowed - No other concurrent cancer therapy - No other concurrent investigational agents Unspecified Childhood Solid Tumor, Protocol Specific Neoplasms PRIMARY OBJECTIVES: I. To estimate the maximum tolerable dose (MTD) of bevacizumab by dose escalation to a maximum of 15mg/kg, even if MTD is not reached, administered as an intravenous infusion, every 2 weeks to children with refractory solid tumors. --- G20210A --- --- G20210A ---

5 A Multicenter, Multinational Study to Assess the Safety and Efficacy of Antithrombin Alfa in Hereditary Antithrombin (AT) Deficient Patients in High-Risk Situations for Thrombosis

Patients with hereditary antithrombin deficiency are at increased risk of venous thrombosis and pulmonary embolism, particularly during certain high risk procedures. The trial focused on patients with confirmed hereditary antithrombin deficiency who were undergoing a surgical procedure or induced/spontaneous labor and delivery, and/or caesarean section. The study assessed the incidence of thromboembolic events following prophylactic intravenous administration of recombinant human antithrombin (rhAT) to patients with hereditary antithrombin (AT) deficiency in situations usually associated with a high risk for thromboembolic events.

NCT00110513 Antithrombin III Deficiency Biological: Recombinant human antithrombin (rhAT)

MeSH:Antithrombin III Deficiency

HPO:Reduced antithrombin III activity

activated protein C(APC) resistance/Factor V Leiden, Protein S or C deficiency, prothrombin gene mutation (G20210A), or acquired (lupus anticoagulant) thrombophilic disorder). --- G20210A ---

In September 2006, GTC Biotherapeutics modified exclusion criteria 1 (below) to allow for the participation of previously excluded patients with the hereditary thrombophilic disorders Factor V Leiden and prothrombin gene mutation (G20210A). --- G20210A ---

6 Low Molecular Weight Heparin Vs No Treatment in Pregnant Women With Previous Preeclampsia or Fetal Growth Restriction Who Were Heterozygote for Factor V Leiden or Prothrombin Gene G20210A Mutation

The objective of this trial will be to determine whether prophylactic low-molecular weight heparin therapy in pregnant women with the heterozygous Factor V Leiden and G20210A prothrombin gene mutations thrombophilia and a history of severe preeclampsia and/or severe fetal growth restriction reduces the risk of the composite outcome of preeclampsia, fetal growth restriction, or both.

NCT00260520 Preeclampsia Drug: Dalteparin

MeSH:Pre-Eclampsia Fetal Growth Retardation

HPO:Intrauterine growth retardation Preeclampsia Toxemia of pregnancy

Low Molecular Weight Heparin Vs No Treatment in Pregnant Women With Previous Preeclampsia or Fetal Growth Restriction Who Were Heterozygote for Factor V Leiden or Prothrombin Gene G20210A Mutation. --- G20210A ---

LMWH to Prevent Preeclampsia and Fetal Growth Restriction The objective of this trial will be to determine whether prophylactic low-molecular weight heparin therapy in pregnant women with the heterozygous Factor V Leiden and G20210A prothrombin gene mutations thrombophilia and a history of severe preeclampsia and/or severe fetal growth restriction reduces the risk of the composite outcome of preeclampsia, fetal growth restriction, or both. --- G20210A ---

Inclusion Criteria: - Previous severe preeclampsia - Previous severe fetal growth restriction - Heterozygous Factor V Leiden - Heterozygous G20210A prothrombin gene mutations Exclusion Criteria: - renal disease - chronic hypertension - preexisting diabetes mellitus - homozygosity for Factor V Leiden - homozygosity for prothrombin G20210A mutation - hyperhomocysteinemia - protein C deficency - protein S deficency - antithrombin deficiency - positive anticardiolipin antibodies - positive lupus anticoagulant Inclusion Criteria: - Previous severe preeclampsia - Previous severe fetal growth restriction - Heterozygous Factor V Leiden - Heterozygous G20210A prothrombin gene mutations Exclusion Criteria: - renal disease - chronic hypertension - preexisting diabetes mellitus - homozygosity for Factor V Leiden - homozygosity for prothrombin G20210A mutation - hyperhomocysteinemia - protein C deficency - protein S deficency - antithrombin deficiency - positive anticardiolipin antibodies - positive lupus anticoagulant Preeclampsia Pre-Eclampsia Fetal Growth Retardation The objective of this trial will be to determine whether prophylactic low-molecular weight heparin therapy in pregnant women with the heterozygous Factor V Leiden and G20210A prothrombin gene mutations thrombophilia and a history of severe preeclampsia and/or severe fetal growth restriction reduces the risk of the composite outcome of preeclampsia, fetal growth restriction, or both. --- G20210A ---

Inclusion Criteria: - Previous severe preeclampsia - Previous severe fetal growth restriction - Heterozygous Factor V Leiden - Heterozygous G20210A prothrombin gene mutations Exclusion Criteria: - renal disease - chronic hypertension - preexisting diabetes mellitus - homozygosity for Factor V Leiden - homozygosity for prothrombin G20210A mutation - hyperhomocysteinemia - protein C deficency - protein S deficency - antithrombin deficiency - positive anticardiolipin antibodies - positive lupus anticoagulant Inclusion Criteria: - Previous severe preeclampsia - Previous severe fetal growth restriction - Heterozygous Factor V Leiden - Heterozygous G20210A prothrombin gene mutations Exclusion Criteria: - renal disease - chronic hypertension - preexisting diabetes mellitus - homozygosity for Factor V Leiden - homozygosity for prothrombin G20210A mutation - hyperhomocysteinemia - protein C deficency - protein S deficency - antithrombin deficiency - positive anticardiolipin antibodies - positive lupus anticoagulant Preeclampsia Pre-Eclampsia Fetal Growth Retardation The objective of this trial will be to determine whether prophylactic low-molecular weight heparin therapy in pregnant women with the heterozygous Factor V Leiden and G20210A prothrombin gene mutations thrombophilia and a history of severe preeclampsia and/or severe fetal growth restriction reduces the risk of the composite outcome of preeclampsia, fetal growth restriction, or both. --- G20210A --- --- G20210A ---

Inclusion Criteria: - Previous severe preeclampsia - Previous severe fetal growth restriction - Heterozygous Factor V Leiden - Heterozygous G20210A prothrombin gene mutations Exclusion Criteria: - renal disease - chronic hypertension - preexisting diabetes mellitus - homozygosity for Factor V Leiden - homozygosity for prothrombin G20210A mutation - hyperhomocysteinemia - protein C deficency - protein S deficency - antithrombin deficiency - positive anticardiolipin antibodies - positive lupus anticoagulant Inclusion Criteria: - Previous severe preeclampsia - Previous severe fetal growth restriction - Heterozygous Factor V Leiden - Heterozygous G20210A prothrombin gene mutations Exclusion Criteria: - renal disease - chronic hypertension - preexisting diabetes mellitus - homozygosity for Factor V Leiden - homozygosity for prothrombin G20210A mutation - hyperhomocysteinemia - protein C deficency - protein S deficency - antithrombin deficiency - positive anticardiolipin antibodies - positive lupus anticoagulant Preeclampsia Pre-Eclampsia Fetal Growth Retardation The objective of this trial will be to determine whether prophylactic low-molecular weight heparin therapy in pregnant women with the heterozygous Factor V Leiden and G20210A prothrombin gene mutations thrombophilia and a history of severe preeclampsia and/or severe fetal growth restriction reduces the risk of the composite outcome of preeclampsia, fetal growth restriction, or both. --- G20210A --- --- G20210A --- --- G20210A ---

Inclusion Criteria: - Previous severe preeclampsia - Previous severe fetal growth restriction - Heterozygous Factor V Leiden - Heterozygous G20210A prothrombin gene mutations Exclusion Criteria: - renal disease - chronic hypertension - preexisting diabetes mellitus - homozygosity for Factor V Leiden - homozygosity for prothrombin G20210A mutation - hyperhomocysteinemia - protein C deficency - protein S deficency - antithrombin deficiency - positive anticardiolipin antibodies - positive lupus anticoagulant Inclusion Criteria: - Previous severe preeclampsia - Previous severe fetal growth restriction - Heterozygous Factor V Leiden - Heterozygous G20210A prothrombin gene mutations Exclusion Criteria: - renal disease - chronic hypertension - preexisting diabetes mellitus - homozygosity for Factor V Leiden - homozygosity for prothrombin G20210A mutation - hyperhomocysteinemia - protein C deficency - protein S deficency - antithrombin deficiency - positive anticardiolipin antibodies - positive lupus anticoagulant Preeclampsia Pre-Eclampsia Fetal Growth Retardation The objective of this trial will be to determine whether prophylactic low-molecular weight heparin therapy in pregnant women with the heterozygous Factor V Leiden and G20210A prothrombin gene mutations thrombophilia and a history of severe preeclampsia and/or severe fetal growth restriction reduces the risk of the composite outcome of preeclampsia, fetal growth restriction, or both. --- G20210A --- --- G20210A --- --- G20210A --- --- G20210A ---

Inclusion Criteria: - Previous severe preeclampsia - Previous severe fetal growth restriction - Heterozygous Factor V Leiden - Heterozygous G20210A prothrombin gene mutations Exclusion Criteria: - renal disease - chronic hypertension - preexisting diabetes mellitus - homozygosity for Factor V Leiden - homozygosity for prothrombin G20210A mutation - hyperhomocysteinemia - protein C deficency - protein S deficency - antithrombin deficiency - positive anticardiolipin antibodies - positive lupus anticoagulant Inclusion Criteria: - Previous severe preeclampsia - Previous severe fetal growth restriction - Heterozygous Factor V Leiden - Heterozygous G20210A prothrombin gene mutations Exclusion Criteria: - renal disease - chronic hypertension - preexisting diabetes mellitus - homozygosity for Factor V Leiden - homozygosity for prothrombin G20210A mutation - hyperhomocysteinemia - protein C deficency - protein S deficency - antithrombin deficiency - positive anticardiolipin antibodies - positive lupus anticoagulant Preeclampsia Pre-Eclampsia Fetal Growth Retardation The objective of this trial will be to determine whether prophylactic low-molecular weight heparin therapy in pregnant women with the heterozygous Factor V Leiden and G20210A prothrombin gene mutations thrombophilia and a history of severe preeclampsia and/or severe fetal growth restriction reduces the risk of the composite outcome of preeclampsia, fetal growth restriction, or both. --- G20210A --- --- G20210A --- --- G20210A --- --- G20210A --- --- G20210A ---

7 Use of Whole Blood and Cell-rich Coagulation Assays for the Detection of Non-Overt DIC in Sepsis

Sepsis is the 13th most common cause of death in the United States, causing approximately 210,000 deaths per year. Once DIC has developed, irreversible organ injury has already occurred and the mortality rate is 70%. Inhibition of systemic coagulation with activated protein C concentrate has been the only therapy for sepsis introduced in the past several decades which has improved outcomes. Elucidation of the coagulopathic mechanisms early in the development of DIC may give rise to targeted therapies and strategies for early intervention. We hypothesize that an increase in endogenous thrombin potential precedes the development of overt DIC by a clinically significant time period. Our primary objective is to determine if endogenous thrombin potential (ETP) measured at first diagnosis of sepsis prior to the onset of DIC and organ failure is predictive of overt DIC and/or poor outcome. We will compare ETP to standard coagulation assays and the clinical assessment of DIC using the ISTH criteria for overt DIC. A secondary objective of this study is to determine if host coagulation variables predispose to the development of DIC and poor clinical outcome during sepsis.

NCT00299949 Sepsis Disseminated Intravascular Coagulation

MeSH:Sepsis Disseminated Intravascular Coagulation

HPO:Disseminated intravascular coagulation Sepsis

Cbc, PT/PTT, Fibrinogen, d-dimer, Protein C activity, Protein S activity, ATIII activity, Factor V Leiden mutation, Prothrombin G20210A mutation analysis will be performed in Memorial Herman Hospital clinical laboratories. --- G20210A ---

The secondary objective will be to compare host coagulation variables, including ETP, roTEG, Pro C, Pro S, ATIII, FVL, and prothrombin G20210A mutation at presentation, with the secondary outcome measures of 28-day mortality and organ dysfunction. --- G20210A ---

8 Phase III Study Analyzing the Effectiveness of Dalteparin Therapy as Intervention in Recurrent Pregnancy Loss

With this clinical trial the investigators will analyze whether the rate of pregnancy losses before the 24th week of gestation can be reduced by dalteparin treatment in habitual aborters.

NCT00400387 Abortion, Habitual Drug: Fragmin P Forte (dalteparin sodium) Dietary Supplement: Multivitamin supplement

MeSH:Abortion, Habitual

Likewise, other thrombophilic risk factors including factor II G20210A, hyperhomocysteinemia, protein C, protein S and antithrombin deficiencies have also been associated with RPL (Sanson 1996; Brenner 1999). --- G20210A ---

9 The Negative Predictive Value of D-dimer on the Risk of Recurrent Venous Thromboembolism in Patients With Multiple Previous Events: a Prospective Cohort Study

Optimal duration of oral anticoagulant therapy in patients with recurrent episodes of venous thromboembolism (VTE) is a matter of debate and recommendations are based on inadequate evidence. More than 12 months of treatment are currently recommended, and the grade of recommendation is low. The PROLONG study has recently evaluated the predictive role of D-dimer measurement after withholding oral anticoagulant treatment in patients with a first episode of VTE. Patients with a positive D-dimer had a significantly higher incidence of VTE recurrences than patients with a negative D-dimer and required resumption of the antithrombotic treatment. Based on the results of this and of previous cohort studies, it appears safe to withhold treatment in patients with negative D-dimer values and to continue treatment in patients with altered D-dimer levels. Aim of this study is therefore to assess the negative predictive value of D-dimer also in patients with recurrent VTE and to evaluate the clinical utility of this approach in this patient setting.

NCT00428441 Venous Thromboembolism Drug: Warfarin

MeSH:Thromboembolism Venous Thromboembolism

HPO:Thromboembolism

Inclusion Criteria: - Patients with at least two episodes of objectively documented venous thromboembolism (at least one proximal deep vein thrombosis or pulmonary embolism) - Ongoing treatment with oral anticoagulants for at least a) 12 months in case idiopathic DVT was the last event; b) 6 months in all other cases - Age > 18 years - Informed consent provided Exclusion Criteria: - Pregnancy/puerperium - One or more episodes of massive pulmonary embolism - Last event isolated idiopathic pulmonary embolism - Two or more idiopathic VTE events - First degree relatives with recurrent VTE - Right ventricular disfunction or pulmonary hypertension - Active cancer - Antiphospholipid antibodies syndrome - Antithrombin deficiency - Homozygous Factor V Leiden or G20210A prothrombin mutation - Heterozygous Factor V Leiden and G20210A prothrombin mutation - Concomitant congenital thrombophilic mutations - Concomitant indications to long term oral anticoagulant treatment - Severe cardiorespiratory insufficiency - Severe liver or renal disease (creatinine clearance > 2 mg/dL) - Limited life expectancy - Geographic inaccessibility Inclusion Criteria: - Patients with at least two episodes of objectively documented venous thromboembolism (at least one proximal deep vein thrombosis or pulmonary embolism) - Ongoing treatment with oral anticoagulants for at least a) 12 months in case idiopathic DVT was the last event; b) 6 months in all other cases - Age > 18 years - Informed consent provided Exclusion Criteria: - Pregnancy/puerperium - One or more episodes of massive pulmonary embolism - Last event isolated idiopathic pulmonary embolism - Two or more idiopathic VTE events - First degree relatives with recurrent VTE - Right ventricular disfunction or pulmonary hypertension - Active cancer - Antiphospholipid antibodies syndrome - Antithrombin deficiency - Homozygous Factor V Leiden or G20210A prothrombin mutation - Heterozygous Factor V Leiden and G20210A prothrombin mutation - Concomitant congenital thrombophilic mutations - Concomitant indications to long term oral anticoagulant treatment - Severe cardiorespiratory insufficiency - Severe liver or renal disease (creatinine clearance > 2 mg/dL) - Limited life expectancy - Geographic inaccessibility Venous Thromboembolism Thromboembolism Venous Thromboembolism null --- G20210A ---

Inclusion Criteria: - Patients with at least two episodes of objectively documented venous thromboembolism (at least one proximal deep vein thrombosis or pulmonary embolism) - Ongoing treatment with oral anticoagulants for at least a) 12 months in case idiopathic DVT was the last event; b) 6 months in all other cases - Age > 18 years - Informed consent provided Exclusion Criteria: - Pregnancy/puerperium - One or more episodes of massive pulmonary embolism - Last event isolated idiopathic pulmonary embolism - Two or more idiopathic VTE events - First degree relatives with recurrent VTE - Right ventricular disfunction or pulmonary hypertension - Active cancer - Antiphospholipid antibodies syndrome - Antithrombin deficiency - Homozygous Factor V Leiden or G20210A prothrombin mutation - Heterozygous Factor V Leiden and G20210A prothrombin mutation - Concomitant congenital thrombophilic mutations - Concomitant indications to long term oral anticoagulant treatment - Severe cardiorespiratory insufficiency - Severe liver or renal disease (creatinine clearance > 2 mg/dL) - Limited life expectancy - Geographic inaccessibility Inclusion Criteria: - Patients with at least two episodes of objectively documented venous thromboembolism (at least one proximal deep vein thrombosis or pulmonary embolism) - Ongoing treatment with oral anticoagulants for at least a) 12 months in case idiopathic DVT was the last event; b) 6 months in all other cases - Age > 18 years - Informed consent provided Exclusion Criteria: - Pregnancy/puerperium - One or more episodes of massive pulmonary embolism - Last event isolated idiopathic pulmonary embolism - Two or more idiopathic VTE events - First degree relatives with recurrent VTE - Right ventricular disfunction or pulmonary hypertension - Active cancer - Antiphospholipid antibodies syndrome - Antithrombin deficiency - Homozygous Factor V Leiden or G20210A prothrombin mutation - Heterozygous Factor V Leiden and G20210A prothrombin mutation - Concomitant congenital thrombophilic mutations - Concomitant indications to long term oral anticoagulant treatment - Severe cardiorespiratory insufficiency - Severe liver or renal disease (creatinine clearance > 2 mg/dL) - Limited life expectancy - Geographic inaccessibility Venous Thromboembolism Thromboembolism Venous Thromboembolism null --- G20210A --- --- G20210A ---

Inclusion Criteria: - Patients with at least two episodes of objectively documented venous thromboembolism (at least one proximal deep vein thrombosis or pulmonary embolism) - Ongoing treatment with oral anticoagulants for at least a) 12 months in case idiopathic DVT was the last event; b) 6 months in all other cases - Age > 18 years - Informed consent provided Exclusion Criteria: - Pregnancy/puerperium - One or more episodes of massive pulmonary embolism - Last event isolated idiopathic pulmonary embolism - Two or more idiopathic VTE events - First degree relatives with recurrent VTE - Right ventricular disfunction or pulmonary hypertension - Active cancer - Antiphospholipid antibodies syndrome - Antithrombin deficiency - Homozygous Factor V Leiden or G20210A prothrombin mutation - Heterozygous Factor V Leiden and G20210A prothrombin mutation - Concomitant congenital thrombophilic mutations - Concomitant indications to long term oral anticoagulant treatment - Severe cardiorespiratory insufficiency - Severe liver or renal disease (creatinine clearance > 2 mg/dL) - Limited life expectancy - Geographic inaccessibility Inclusion Criteria: - Patients with at least two episodes of objectively documented venous thromboembolism (at least one proximal deep vein thrombosis or pulmonary embolism) - Ongoing treatment with oral anticoagulants for at least a) 12 months in case idiopathic DVT was the last event; b) 6 months in all other cases - Age > 18 years - Informed consent provided Exclusion Criteria: - Pregnancy/puerperium - One or more episodes of massive pulmonary embolism - Last event isolated idiopathic pulmonary embolism - Two or more idiopathic VTE events - First degree relatives with recurrent VTE - Right ventricular disfunction or pulmonary hypertension - Active cancer - Antiphospholipid antibodies syndrome - Antithrombin deficiency - Homozygous Factor V Leiden or G20210A prothrombin mutation - Heterozygous Factor V Leiden and G20210A prothrombin mutation - Concomitant congenital thrombophilic mutations - Concomitant indications to long term oral anticoagulant treatment - Severe cardiorespiratory insufficiency - Severe liver or renal disease (creatinine clearance > 2 mg/dL) - Limited life expectancy - Geographic inaccessibility Venous Thromboembolism Thromboembolism Venous Thromboembolism null --- G20210A --- --- G20210A --- --- G20210A ---

Inclusion Criteria: - Patients with at least two episodes of objectively documented venous thromboembolism (at least one proximal deep vein thrombosis or pulmonary embolism) - Ongoing treatment with oral anticoagulants for at least a) 12 months in case idiopathic DVT was the last event; b) 6 months in all other cases - Age > 18 years - Informed consent provided Exclusion Criteria: - Pregnancy/puerperium - One or more episodes of massive pulmonary embolism - Last event isolated idiopathic pulmonary embolism - Two or more idiopathic VTE events - First degree relatives with recurrent VTE - Right ventricular disfunction or pulmonary hypertension - Active cancer - Antiphospholipid antibodies syndrome - Antithrombin deficiency - Homozygous Factor V Leiden or G20210A prothrombin mutation - Heterozygous Factor V Leiden and G20210A prothrombin mutation - Concomitant congenital thrombophilic mutations - Concomitant indications to long term oral anticoagulant treatment - Severe cardiorespiratory insufficiency - Severe liver or renal disease (creatinine clearance > 2 mg/dL) - Limited life expectancy - Geographic inaccessibility Inclusion Criteria: - Patients with at least two episodes of objectively documented venous thromboembolism (at least one proximal deep vein thrombosis or pulmonary embolism) - Ongoing treatment with oral anticoagulants for at least a) 12 months in case idiopathic DVT was the last event; b) 6 months in all other cases - Age > 18 years - Informed consent provided Exclusion Criteria: - Pregnancy/puerperium - One or more episodes of massive pulmonary embolism - Last event isolated idiopathic pulmonary embolism - Two or more idiopathic VTE events - First degree relatives with recurrent VTE - Right ventricular disfunction or pulmonary hypertension - Active cancer - Antiphospholipid antibodies syndrome - Antithrombin deficiency - Homozygous Factor V Leiden or G20210A prothrombin mutation - Heterozygous Factor V Leiden and G20210A prothrombin mutation - Concomitant congenital thrombophilic mutations - Concomitant indications to long term oral anticoagulant treatment - Severe cardiorespiratory insufficiency - Severe liver or renal disease (creatinine clearance > 2 mg/dL) - Limited life expectancy - Geographic inaccessibility Venous Thromboembolism Thromboembolism Venous Thromboembolism null --- G20210A --- --- G20210A --- --- G20210A --- --- G20210A ---

10 Chemotherapy With or Without Preventive Anticoagulation for Metastatic Cancer of the Pancreas

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Anticoagulants, such as dalteparin, may help prevent blood clots from forming in patients being treated with chemotherapy. It is not yet known whether gemcitabine is more effective when given alone or together with dalteparin and/or capecitabine in treating patients with pancreatic cancer. PURPOSE: This randomized phase III trial is studying whether dalteparin prevents blood clots in patients with pancreatic cancer receiving treatment with different combinations of gemcitabine and capecitabine.

NCT00662688 Chemotherapeutic Agent Toxicity Pancreatic Cancer Thromboembolism Drug: daltéparine Drug: Chemotherapy at the investigator's discretion

MeSH:Pancreatic Neoplasms Thromboembolism

HPO:Neoplasm of the pancreas Thromboembolism

Blood is examined for biomarkers, resistance to activated protein C, and mutations (Leiden V factor, mutation G20210A, and the factor II gene). --- G20210A ---

11 Essai thérapeutique randomisé Multicentrique en Double Insu, Comparant l'énoxaparine 40mg Versus Placebo, en Une Injection Sous-cutanée Quotidienne, Dans Les Fausses Couches spontanées récurrentes inexpliquées

Standard investigations fail to reveal any apparent cause in 50% of the cases of recurrent spontaneous abortion. Prothrombotic mechanisms were initially evoked. Factor V Leiden, Prothrombin G20210A mutation and protein S deficiency are implicated in the meta-analysis of Rey (Lancet).However, they do not account for a large number of miscarriages.Gris JC and coworkers (Blood 2004)carried out an open trial, low-molecular-weight heparin versus low-dose aspirin, in women with one fetal loss and with a constitutional thrombophilic disorder. They conclude for a benefit action of Low-molecular-weight heparin. There is actually no trials concerning women with unexplained recurrent abortions and without known thrombophilia. Nevertheless,aspirin or enoxaparin are often prescribed. It is time to assess these practices. We therefore initiate a multisite, double blind randomized study, enoxaparine versus placebo, in women without known thrombophilia, which experienced unexplained recurrent abortions.

NCT00740545 Alive and Viable Births Drug: enoxaparine 40 mg daily Drug: placebo

Factor V Leiden, Prothrombin G20210A mutation and protein S deficiency are implicated in the meta-analysis of Rey (Lancet).However, they do not account for a large number of miscarriages.Gris JC and coworkers (Blood 2004)carried out an open trial, low-molecular-weight heparin versus low-dose aspirin, in women with one fetal loss and with a constitutional thrombophilic disorder. --- G20210A ---

Inclusion Criteria: - Women between 18 and 45 years - 2 or more consecutive spontaneous abortions before the 15th week of pregnancy - Unexplained abortions - No maternal or paternal characterized chromosomal aberration - No Anti-phospholipid Syndrome - No anatomical abnormality possibly responsible for abortion - No Factor V Leiden - No Prothrombin G20210A mutation - No protein S deficiency - No protein C deficiency - No Anti thrombin 3 deficiency - Proved pregnancy Exclusion Criteria: - Contraindications of enoxaparine 4000 U per day - Women with risk of venous thromboembolism during pregnancy - No regular anticoagulation or antiplatelet treatment - Blood Hemoglobin level below 10g/dl - Blood platelet level below 150 000/mm3 - Creatinine clearance below 30ml/mn - Anomaly of the coagulation tests - No informed consent Inclusion Criteria: - Women between 18 and 45 years - 2 or more consecutive spontaneous abortions before the 15th week of pregnancy - Unexplained abortions - No maternal or paternal characterized chromosomal aberration - No Anti-phospholipid Syndrome - No anatomical abnormality possibly responsible for abortion - No Factor V Leiden - No Prothrombin G20210A mutation - No protein S deficiency - No protein C deficiency - No Anti thrombin 3 deficiency - Proved pregnancy Exclusion Criteria: - Contraindications of enoxaparine 4000 U per day - Women with risk of venous thromboembolism during pregnancy - No regular anticoagulation or antiplatelet treatment - Blood Hemoglobin level below 10g/dl - Blood platelet level below 150 000/mm3 - Creatinine clearance below 30ml/mn - Anomaly of the coagulation tests - No informed consent Alive and Viable Births null --- G20210A ---

Inclusion Criteria: - Women between 18 and 45 years - 2 or more consecutive spontaneous abortions before the 15th week of pregnancy - Unexplained abortions - No maternal or paternal characterized chromosomal aberration - No Anti-phospholipid Syndrome - No anatomical abnormality possibly responsible for abortion - No Factor V Leiden - No Prothrombin G20210A mutation - No protein S deficiency - No protein C deficiency - No Anti thrombin 3 deficiency - Proved pregnancy Exclusion Criteria: - Contraindications of enoxaparine 4000 U per day - Women with risk of venous thromboembolism during pregnancy - No regular anticoagulation or antiplatelet treatment - Blood Hemoglobin level below 10g/dl - Blood platelet level below 150 000/mm3 - Creatinine clearance below 30ml/mn - Anomaly of the coagulation tests - No informed consent Inclusion Criteria: - Women between 18 and 45 years - 2 or more consecutive spontaneous abortions before the 15th week of pregnancy - Unexplained abortions - No maternal or paternal characterized chromosomal aberration - No Anti-phospholipid Syndrome - No anatomical abnormality possibly responsible for abortion - No Factor V Leiden - No Prothrombin G20210A mutation - No protein S deficiency - No protein C deficiency - No Anti thrombin 3 deficiency - Proved pregnancy Exclusion Criteria: - Contraindications of enoxaparine 4000 U per day - Women with risk of venous thromboembolism during pregnancy - No regular anticoagulation or antiplatelet treatment - Blood Hemoglobin level below 10g/dl - Blood platelet level below 150 000/mm3 - Creatinine clearance below 30ml/mn - Anomaly of the coagulation tests - No informed consent Alive and Viable Births null --- G20210A --- --- G20210A ---

12 Prophylactic Enoxaparin Dosing for Prevention of Venous Thromboembolism in Pregnancy.

Enoxaparin is a type of low molecular weight heparin (LMWH), or anticoagulant, used to prevent and treat blood clots. Formation of blood clots, or venous thromboemboli (VTE) in pregnancy can have dangerous and even life-threatening effects on the mother and fetus. Enoxaparin is the preferred medicine to prevent clotting in pregnant patients who are at risk for VTE, because it has been studied to be safe and effective in pregnancy without any harms to the fetus. Although this medication is routinely used and is recommended by several prominent medical groups, the optimal dosing for prevention of VTE is still unclear. The range of standardly prescribed dosing regimens of Enoxaparin includes 40mg daily and 1mg/kg daily, but these two dosing strategies have never been compared in a head to head fashion.

NCT00878826 Venous Thrombosis Drug: Enoxaparin

MeSH:Thrombosis Thromboembolism Venous Thromboembolism Venous Thrombosis

HPO:Deep venous thrombosis Thromboembolism Venous thrombosis

Inclusion Criteria: 1. >18 years of age 2. Warrants prophylaxis against venous thromboembolism in pregnancy according to American College of Obstetrics and Gynecology Practice Bulletin 2000, reaffirmed in 2008: - history of idiopathic thrombosis - history of thrombosis related to pregnancy or oral contraceptive use - history of thrombosis accompanied by an underlying thrombophilia other than homozygous for the factor V Leiden mutation, heterozygous for both the factor V Leiden and the prothrombin G20210A mutation, or AT-III deficiency - without a history of thrombosis but who have an underlying thrombophilia and a strong family history of thrombosis - Known thrombophilia except for those listed above, with a history of adverse pregnancy outcome (APO) as defined by: ¡Ý3 pregnancy losses in the 1st trimester, ¡Ý2 pregnancy losses/stillbirth in 2nd trimester, ¡Ý1 pregnancy loss/intrauterine fetal demise (IUFD) in the 3rd trimester, intrauterine growth restriction (IUGR), abruptio placentae, or severe pre-Eclampsia prior to 34 weeks gestation. --- G20210A ---

Exclusion Criteria: 1. Need for therapeutic-level anticoagulation as determined by physician 2. Renal disease as defined by serum creatinine >1.0 3. Weight >90kg 4. Allergy to enoxaparin Inclusion Criteria: 1. >18 years of age 2. Warrants prophylaxis against venous thromboembolism in pregnancy according to American College of Obstetrics and Gynecology Practice Bulletin 2000, reaffirmed in 2008: - history of idiopathic thrombosis - history of thrombosis related to pregnancy or oral contraceptive use - history of thrombosis accompanied by an underlying thrombophilia other than homozygous for the factor V Leiden mutation, heterozygous for both the factor V Leiden and the prothrombin G20210A mutation, or AT-III deficiency - without a history of thrombosis but who have an underlying thrombophilia and a strong family history of thrombosis - Known thrombophilia except for those listed above, with a history of adverse pregnancy outcome (APO) as defined by: ¡Ý3 pregnancy losses in the 1st trimester, ¡Ý2 pregnancy losses/stillbirth in 2nd trimester, ¡Ý1 pregnancy loss/intrauterine fetal demise (IUFD) in the 3rd trimester, intrauterine growth restriction (IUGR), abruptio placentae, or severe pre-Eclampsia prior to 34 weeks gestation. --- G20210A ---

13 Omega-3 Supplementation Decreases Inflammation and Fetal Obesity in Pregnancy

Randomized, double-blind placebo controlled trial of fish oil to decrease inflammation in pregnancy.

NCT00957476 Inflammation Obesity Pregnancy Fetal Growth Dietary Supplement: Omega-3 Fish Oil

MeSH:Obesity Inflammation

HPO:Obesity

- Moderate or high titer IgG anticardiolipin antibodies or prolonged activated PTT or other indication of presence of lupus anticoagulant, homozygous for prothrombin gene (G20210A) mutation, antithrombin III deficiency. --- G20210A ---

14 VeraCode Genotyping Test for Factor V and Factor II on the BeadXpress System

As an external validation test of the performance of the VeraCode Genotyping Test for Factor V and Factor II on the BeadXpress System, clinical trials will be conducted at three sites. This study will assess genotyping accuracy as compared to bidirectional sequencing and genotyping reproducibility across variables such as user, day, and site.

NCT00959504 Detection and Genotyping of Factor V and Factor II Poi Detection and Genotyping of Factor V and Factor II Point Mutations

Detection of Factor V Leiden G1691A and Factor II (Prothrombin) G20210A Point Mutations in DNA As an external validation test of the performance of the VeraCode Genotyping Test for Factor V and Factor II on the BeadXpress System, clinical trials will be conducted at three sites. --- G1691A --- --- G20210A ---

15 Correlation of Genetic Polymorphism and Livedo Vasculitis

Livedo vasculitis is disease with recurrent courses of painful foot or ankle ulcerations, followed by healed white scars. The actual mechanism of its pathophysiology is not yet clear. It has been reported to be associated with some gene mutations, for example, factor V Leiden gene. This study is aimed to find the possible relation of these gene mutations in Taiwanese patients.

NCT00975871 Livedo Vasculitis Livedoid Vasculitis Livedoid Vasculopathy Genetic Pleomorphism Leiden Mutation

MeSH:Vasculitis

HPO:Vasculitis

It has been reported to be related to factor V Leiden mutation (heterozygous) (22.2%), prothrombin G20210A gene mutation (8.3%), PAI promotor 4G/4G genotype and methylenetetrahydrofolate reductase (MTHFR) C677T mutation in about total 30% livedo vasculitis patients. --- G20210A ---

16 Low Molecular Weight Heparin, Enoxaparin, to Prevent Adverse Maternal and Perinatal Outcomes in Women With Previous Severe Preeclampsia at Less Than 34 Weeks' Gestation. A Prospective Randomized Trial

Preeclampsia (PE) complicates 2-8% of pregnancies. It is associated with an increased risk of adverse maternal (death, eclampsia, abruptio placenta, HELLP syndrome) and perinatal (perinatal death, growth restriction, prematurity) outcomes. The only definite treatment of PE remains pregnancy termination. Therefore, prevention of PE remains an important challenge. Low dose aspirin may be used in the prevention of PE, particularly in women who had a severe preeclampsia before 34 weeks. Its efficiency, however, is very weak. Recently, it has been suggested that low molecular weight heparin might be useful in the prevention of PE. The aim of this study is to analyze the usefulness of the enoxaparin 4000 UI/day in the prevention of a composite maternal or perinatal morbidity (occurrence of one of the following events: maternal death, PE, fetal growth retardation, abruptio placenta, perinatal death) in women who previously had a severe preeclampsia at less than 34 weeks' gestation. To answer this question, the investigators propose to conduct a multicenter prospective randomized trial that will compare two groups in parallel: a group where women will have an association of enoxaparin 4000 U/day and aspirin 100 mg/day and another group where women would have only aspirin 100 mg/day. The number of patients needed is 255 (amendment n°2-approved 06/12/2011) .

NCT00986765 Preeclampsia Drug: Lovenox® (enoxaparin) Drug: Aspegic ® (Aspirin)

MeSH:Pre-Eclampsia

HPO:Preeclampsia Toxemia of pregnancy

Recurrence of preeclampsia controlled for thrombophilia analysis (polymorphism of factor V Leiden, prothrombin G20210A gene polymorphism). --- G20210A ---

17 Low Molecular Weight Heparin for Pregnant Women With Thrombophilia: a Prospective, Randomized, Open Trial

The purpose of this study is to investigate whether heparin is an effective treatment in pregnant women at risk for thrombosis and other pregnancy-associated complications.

NCT01019655 Pregnancy and Thrombophilia Drug: Nadroparin calcium

MeSH:Thrombophilia

HPO:Hypercoagulability

Inclusion Criteria: - Pregnant women with a singleton pregnancy - Age >18 years - Ability to understand informed consent form Exclusion Criteria: - Allergy/hypersensitivity for nadroparin calcium - Heparin-associated thrombocytopenia - Organ lesions at risk for bleeding such as acute stomach/bowel ulcers, cerebral hemorrhage, cerebral aneurysm - uncontrolled hypertension - Liver and/or renal dysfunction - Known hematologic disease Inclusion Criteria: - Pregnant women with a singleton pregnancy - Age >18 years - Ability to understand informed consent form Exclusion Criteria: - Allergy/hypersensitivity for nadroparin calcium - Heparin-associated thrombocytopenia - Organ lesions at risk for bleeding such as acute stomach/bowel ulcers, cerebral hemorrhage, cerebral aneurysm - uncontrolled hypertension - Liver and/or renal dysfunction - Known hematologic disease Pregnancy and Thrombophilia Thrombophilia Women with thrombophilia, i.e. carriage of a factor V leiden mutation, a factor II prothrombin G20210A mutation or a reduced amount of antithrombin III, protein C or protein S, are at elevated risk for thrombosis and related sequelae. --- G20210A ---

18 Temozolomide With Irinotecan Versus Temozolomide, Irinotecan Plus Bevacizumab (NSC# 704865) for Recurrent/Refractory Medulloblastoma/CNS PNET of Childhood, a COG Randomized Phase II Screening Trial

This randomized phase II trial studies how well giving temozolomide and irinotecan hydrochloride together with or without bevacizumab works in treating young patients with recurrent or refractory medulloblastoma or central nervous system (CNS) primitive neuroectodermal tumors. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether temozolomide and irinotecan hydrochloride are more effective with or without bevacizumab in treating medulloblastoma or CNS primitive neuroectodermal tumors.

NCT01217437 Recurrent Childhood Medulloblastoma Recurrent Childhood Pineoblastoma Recurrent Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified Biological: Bevacizumab Drug: Irinotecan Hydrochloride Drug: Temozolomide

MeSH:Medulloblastoma Pinealoma

HPO:Medulloblastoma Pineal parenchymal cell neoplasm Pinealoma Pineoblastoma Pineocytoma Supratentorial neoplasm

Inclusion Criteria: - Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible - Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence - Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters - All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment - Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age) - Patients must have a life expectancy of >= 8 weeks - Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea) - Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies - External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry - Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry - Study specific limitations on prior therapy: - Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor - Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry - Patients must have recovered from any surgical procedure before enrolling on this study: - Patients with a major surgical procedure within 28 days prior to enrollment should be excluded - Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded - For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed - There should be no anticipation of need for major surgical procedures during the course of the study - Examples of major, intermediate, or minor surgical procedures: - Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy - Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy - Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis - Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy - Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication - Concomitant medications restrictions: - Growth factor(s): Must not have received within 7 days of entry onto this study - Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days - Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day - Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days) - Platelet count >= 100,000/uL (transfusion independent) - Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows: - =< 0.4 mg/dL (for patients aged 1 month to < 6 months) - =< 0.5 mg/dL (for patients aged 6 months to < 1 year) - =< 0.6 mg/dL (for patients aged 1 to < 2 years) - =< 0.8 mg/dL (for patients aged 2 to < 6 years) - =< 1 mg/dL (for patients aged 6 to < 10 years) - =< 1.2 mg/dL (for patients aged 10 to < 13 years) - =< 1.4 mg/dL (for female patients aged >= 13 years) - =< 1.5 mg/dL (for male patients aged 13 to < 16 years) - =< 1.7 mg/dL (for male patients aged >= 16 years) - Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age - Central nervous system function defined as - Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants - Adequate coagulation defined as - International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal Exclusion Criteria: - Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study - Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry - Patients must not have a known bleeding diathesis or coagulopathy - Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry - Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history - Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment - Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible - Patients must not have serious and inadequately controlled cardiac arrhythmia - Female patients who are pregnant are not eligible for this study - Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed - Female patients of childbearing potential must have a negative pregnancy test - Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy - Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies Inclusion Criteria: - Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible - Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence - Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters - All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment - Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age) - Patients must have a life expectancy of >= 8 weeks - Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea) - Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies - External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry - Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry - Study specific limitations on prior therapy: - Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor - Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry - Patients must have recovered from any surgical procedure before enrolling on this study: - Patients with a major surgical procedure within 28 days prior to enrollment should be excluded - Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded - For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed - There should be no anticipation of need for major surgical procedures during the course of the study - Examples of major, intermediate, or minor surgical procedures: - Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy - Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy - Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis - Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy - Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication - Concomitant medications restrictions: - Growth factor(s): Must not have received within 7 days of entry onto this study - Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days - Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day - Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days) - Platelet count >= 100,000/uL (transfusion independent) - Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows: - =< 0.4 mg/dL (for patients aged 1 month to < 6 months) - =< 0.5 mg/dL (for patients aged 6 months to < 1 year) - =< 0.6 mg/dL (for patients aged 1 to < 2 years) - =< 0.8 mg/dL (for patients aged 2 to < 6 years) - =< 1 mg/dL (for patients aged 6 to < 10 years) - =< 1.2 mg/dL (for patients aged 10 to < 13 years) - =< 1.4 mg/dL (for female patients aged >= 13 years) - =< 1.5 mg/dL (for male patients aged 13 to < 16 years) - =< 1.7 mg/dL (for male patients aged >= 16 years) - Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age - Central nervous system function defined as - Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants - Adequate coagulation defined as - International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal Exclusion Criteria: - Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study - Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry - Patients must not have a known bleeding diathesis or coagulopathy - Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry - Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history - Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment - Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible - Patients must not have serious and inadequately controlled cardiac arrhythmia - Female patients who are pregnant are not eligible for this study - Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed - Female patients of childbearing potential must have a negative pregnancy test - Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy - Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies Recurrent Childhood Medulloblastoma Recurrent Childhood Pineoblastoma Recurrent Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified Medulloblastoma Pinealoma PRIMARY OBJECTIVES: l. --- G20210A ---

Inclusion Criteria: - Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible - Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence - Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters - All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment - Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age) - Patients must have a life expectancy of >= 8 weeks - Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea) - Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies - External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry - Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry - Study specific limitations on prior therapy: - Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor - Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry - Patients must have recovered from any surgical procedure before enrolling on this study: - Patients with a major surgical procedure within 28 days prior to enrollment should be excluded - Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded - For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed - There should be no anticipation of need for major surgical procedures during the course of the study - Examples of major, intermediate, or minor surgical procedures: - Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy - Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy - Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis - Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy - Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication - Concomitant medications restrictions: - Growth factor(s): Must not have received within 7 days of entry onto this study - Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days - Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day - Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days) - Platelet count >= 100,000/uL (transfusion independent) - Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows: - =< 0.4 mg/dL (for patients aged 1 month to < 6 months) - =< 0.5 mg/dL (for patients aged 6 months to < 1 year) - =< 0.6 mg/dL (for patients aged 1 to < 2 years) - =< 0.8 mg/dL (for patients aged 2 to < 6 years) - =< 1 mg/dL (for patients aged 6 to < 10 years) - =< 1.2 mg/dL (for patients aged 10 to < 13 years) - =< 1.4 mg/dL (for female patients aged >= 13 years) - =< 1.5 mg/dL (for male patients aged 13 to < 16 years) - =< 1.7 mg/dL (for male patients aged >= 16 years) - Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age - Central nervous system function defined as - Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants - Adequate coagulation defined as - International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal Exclusion Criteria: - Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study - Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry - Patients must not have a known bleeding diathesis or coagulopathy - Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry - Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history - Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment - Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible - Patients must not have serious and inadequately controlled cardiac arrhythmia - Female patients who are pregnant are not eligible for this study - Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed - Female patients of childbearing potential must have a negative pregnancy test - Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy - Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies Inclusion Criteria: - Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible - Patients must have had histologic verification of the malignancy at original diagnosis or at the time of recurrence - Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) OR diffuse leptomeningeal disease OR clear MRI evidence of disease that may not be measurable in two perpendicular diameters - All patients must have a brain MRI with and without gadolinium and a spine MRI with gadolinium performed within 2 weeks prior to study enrollment - Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2 (use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age) - Patients must have a life expectancy of >= 8 weeks - Patients must have experienced at least one and at most two relapses prior to study enrollment; patients with primary refractory disease are eligible - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study - Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (6 weeks if prior nitrosourea) - Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent; at least 3 weeks for biologic agents with a long half life, such as antibodies - External beam radiation therapy (XRT): Must not have received craniospinal radiotherapy within 24 weeks prior to study entry; the tumor designated as "measurable" for protocol purposes must not have received radiation within 12 weeks prior to study entry); focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry - Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed prior to study entry - Study specific limitations on prior therapy: - Patients must not have previously received bevacizumab, irinotecan, temozolomide or other anti-vascular endothelial growth factor (VEGF) inhibitor - Patients must not be taking enzyme-inducing antiepileptic medicines within 1 week of study entry - Patients must have recovered from any surgical procedure before enrolling on this study: - Patients with a major surgical procedure within 28 days prior to enrollment should be excluded - Patients with an intermediate surgical procedure within 14 days prior to enrollment should be excluded - For minor surgical procedures (including Broviac line or infusaport placement), patients should not receive the first planned dose of bevacizumab until the wound is healed and at least 7 days have elapsed - There should be no anticipation of need for major surgical procedures during the course of the study - Examples of major, intermediate, or minor surgical procedures: - Major procedures: Major craniotomy for tumor resection; organ resection; bowel wall anastomosis; arteriovenous grafts; exploratory laparotomy; thoracotomy - Intermediate procedures: Ventriculoperitoneal (VP)-shunt placement; stereotactic brain biopsy - Minor procedures: Incision and drainage of superficial skin abscesses; punch biopsy of skin lesions; superficial skin wound suturing; bone marrow aspirate and/or biopsy; fine needle aspirations; Broviac line or infusaport placement; paracentesis or thoracocentesis - Please note: Lumbar punctures or placement of peripherally inserted central catheter (PICC) lines are not considered minor procedures and may occur at any time prior to or during therapy - Hypertension must be well controlled (=< 95th percentile for age and height if patient is =< 17 years) on stable doses of medication - Concomitant medications restrictions: - Growth factor(s): Must not have received within 7 days of entry onto this study - Steroids: Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days - Study Specific: Patients must not be currently taking nonsteroidal anti-inflammatory drugs (NSAIDs), clopidrogel, dipyridamole or aspirin therapy > 81 mg/day - Peripheral absolute neutrophil count (ANC) >= 1000/uL (must not have received filgrastim [G-CSF] within the prior 7 days) - Platelet count >= 100,000/uL (transfusion independent) - Hemoglobin >= 8.0 gm/dL (may receive packed red blood cell [PRBC] transfusions) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age/gender as follows: - =< 0.4 mg/dL (for patients aged 1 month to < 6 months) - =< 0.5 mg/dL (for patients aged 6 months to < 1 year) - =< 0.6 mg/dL (for patients aged 1 to < 2 years) - =< 0.8 mg/dL (for patients aged 2 to < 6 years) - =< 1 mg/dL (for patients aged 6 to < 10 years) - =< 1.2 mg/dL (for patients aged 10 to < 13 years) - =< 1.4 mg/dL (for female patients aged >= 13 years) - =< 1.5 mg/dL (for male patients aged 13 to < 16 years) - =< 1.7 mg/dL (for male patients aged >= 16 years) - Urine protein should be screened by dipstick analysis; if protein >= 2+ on dipstick, then urine protein creatinine (UPC) ratio should be calculated; if UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) for age - Central nervous system function defined as - Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants - Adequate coagulation defined as - International normalized ratio (INR)/prothrombin time (PT) =< 1.5 x upper limit of normal Exclusion Criteria: - Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study - Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry - Patients must not have a known bleeding diathesis or coagulopathy - Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry - Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome); testing is not required in patients without thrombophilic history - Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment - Patients with a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months are not eligible - Patients must not have serious and inadequately controlled cardiac arrhythmia - Female patients who are pregnant are not eligible for this study - Female patients who are breastfeeding are not eligible for this study unless they agree not to breastfeed - Female patients of childbearing potential must have a negative pregnancy test - Sexually active patients of childbearing potential must agree to use an effective method of contraception during the study and for at least 6 months after the completion of bevacizumab therapy - Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies Recurrent Childhood Medulloblastoma Recurrent Childhood Pineoblastoma Recurrent Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified Medulloblastoma Pinealoma PRIMARY OBJECTIVES: l. --- G20210A --- --- G20210A ---

19 A Phase II Evaluation of BIBF 1120 in the Treatment of Recurrent or Persistent Endometrial Carcinoma

This phase II trial studies the side effects and how well nintedanib works in treating patients with endometrial cancer that has come back. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

NCT01225887 Endometrial Adenocarcinoma Endometrial Clear Cell Adenocarcinoma Endometrial Mucinous Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Squamous Cell Carcinoma Endometrial Transitional Cell Carcinoma Endometrial Undifferentiated Carcinoma Malignant Uterine Corpus Mixed Epithelial and Mesenchymal Neoplasm Recurrent Uterine Corpus Carcinoma Drug: Nintedanib

MeSH:Carcinoma Adenocarcinoma Carcinoma, Transitional Cell Cystadenocarcinoma, Serous Adenocarcinoma, Mucinous Cystadenocarcinoma Adenocarcinoma, Clear Cell

HPO:Carcinoma

the period of progression free survival for patients with persistent or recurrent endometrial cancer treated with study drug.. Inclusion Criteria: - Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population - Patients must have a GOG performance status of 0, 1, or 2 - Patients must have normal thyroid function; patients with a history of hypothyroidism are eligible, provided it is well controlled on medication - Recovery from effects of recent surgery, radiotherapy, or chemotherapy - Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection) - Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration - Any other prior therapy directed at the malignant tumor, including chemotherapy and immunologic agents, must be discontinued at least three weeks prior to registration - Any prior radiation therapy must be completed at least 4 weeks prior to registration - Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer will be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease - Patients must have NOT received any non-cytotoxic (biologic or targeted) agents, as part of their primary treatment or for management of recurrent or persistent disease; non-cytotoxic (biologic or targeted) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction; prior hormonal therapy is allowed; there is no limit on the number of prior hormonal therapies allowed - Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl - Platelets greater than or equal to 100,000/mcl - Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN) - Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended - Bilirubin must be less than 1.5 X ULN - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be less than 3 X ULN - Alkaline phosphatase must be less than 2.5 X ULN - Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 times the institutional upper limit of normal - Electrocardiogram (EKG) must have corrected QT interval (QTc) < 450 msec without evidence of serious ventricular arrhythmia (ventricular tachycardia lasting more than 3 beats or ventricular fibrillation) - Patients must have signed an approved informed consent and authorization permitting release of personal health information - Patients must meet pre-entry requirements - Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry; women of child-bearing potential must agree to use adequate contraception (two barrier methods of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she is to inform her treating physician immediately; all patients must be willing to take contraception up to three months after the final dose of BIBF 1120 Exclusion Criteria: - Patients who have had prior therapy with BIBF 1120 - Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy - Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease - Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease - Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to the start date of treatment; patients with underlying lesions that caused the fistula or perforation in the past that have not been corrected - Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels - Patients with history of brain metastases, or evidence upon physical examination of active central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases - Uncontrolled hypertension, defined as systolic >= 150 mm Hg or diastolic >= 90 mm Hg - Myocardial infarction or unstable angina within 6 months of study treatment - New York Heart Association (NYHA) class II or greater congestive heart failure - Women with an ejection fraction < institutional lower limit of normal (LLN) - History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication) - Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater peripheral vascular disease - History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of study treatment - Patients undergoing invasive procedures as defined below: major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of treatment; major surgical procedure anticipated during the course of the study; minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of therapy - Patients who are pregnant or nursing - Patients with a history of major thromboembolic event defined as: symptomatic pulmonary embolism (PE), recurrent asymptomatic PE, or recurrent deep venous thrombosis - Prior thrombosis or thromboembolic event due to a known inherited coagulopathy (i.e., antithrombin-III deficiency, protein C or protein S deficiency, factor V Leiden mutation presence, prothrombin G20210A mutation) - Serious infections requiring systemic antibiotics or antiviral therapy including: known active hepatitis B or C infection; known human immunodeficiency virus (HIV) infection - Gastrointestinal (GI) or other medical disorders that would impact ingestion or absorption of the drug - Patients with a history of photosensitivity or who must take agents which increase photosensitivity, e.g. --- G20210A ---

topical retinoids and doxycycline - Patients who are unable to swallow capsules Inclusion Criteria: - Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population - Patients must have a GOG performance status of 0, 1, or 2 - Patients must have normal thyroid function; patients with a history of hypothyroidism are eligible, provided it is well controlled on medication - Recovery from effects of recent surgery, radiotherapy, or chemotherapy - Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection) - Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration - Any other prior therapy directed at the malignant tumor, including chemotherapy and immunologic agents, must be discontinued at least three weeks prior to registration - Any prior radiation therapy must be completed at least 4 weeks prior to registration - Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer will be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease - Patients must have NOT received any non-cytotoxic (biologic or targeted) agents, as part of their primary treatment or for management of recurrent or persistent disease; non-cytotoxic (biologic or targeted) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction; prior hormonal therapy is allowed; there is no limit on the number of prior hormonal therapies allowed - Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl - Platelets greater than or equal to 100,000/mcl - Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN) - Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended - Bilirubin must be less than 1.5 X ULN - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be less than 3 X ULN - Alkaline phosphatase must be less than 2.5 X ULN - Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 times the institutional upper limit of normal - Electrocardiogram (EKG) must have corrected QT interval (QTc) < 450 msec without evidence of serious ventricular arrhythmia (ventricular tachycardia lasting more than 3 beats or ventricular fibrillation) - Patients must have signed an approved informed consent and authorization permitting release of personal health information - Patients must meet pre-entry requirements - Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry; women of child-bearing potential must agree to use adequate contraception (two barrier methods of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she is to inform her treating physician immediately; all patients must be willing to take contraception up to three months after the final dose of BIBF 1120 Exclusion Criteria: - Patients who have had prior therapy with BIBF 1120 - Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy - Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease - Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease - Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to the start date of treatment; patients with underlying lesions that caused the fistula or perforation in the past that have not been corrected - Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels - Patients with history of brain metastases, or evidence upon physical examination of active central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases - Uncontrolled hypertension, defined as systolic >= 150 mm Hg or diastolic >= 90 mm Hg - Myocardial infarction or unstable angina within 6 months of study treatment - New York Heart Association (NYHA) class II or greater congestive heart failure - Women with an ejection fraction < institutional lower limit of normal (LLN) - History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication) - Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater peripheral vascular disease - History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of study treatment - Patients undergoing invasive procedures as defined below: major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of treatment; major surgical procedure anticipated during the course of the study; minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of therapy - Patients who are pregnant or nursing - Patients with a history of major thromboembolic event defined as: symptomatic pulmonary embolism (PE), recurrent asymptomatic PE, or recurrent deep venous thrombosis - Prior thrombosis or thromboembolic event due to a known inherited coagulopathy (i.e., antithrombin-III deficiency, protein C or protein S deficiency, factor V Leiden mutation presence, prothrombin G20210A mutation) - Serious infections requiring systemic antibiotics or antiviral therapy including: known active hepatitis B or C infection; known human immunodeficiency virus (HIV) infection - Gastrointestinal (GI) or other medical disorders that would impact ingestion or absorption of the drug - Patients with a history of photosensitivity or who must take agents which increase photosensitivity, e.g. --- G20210A ---

20 Prospective Study Assessing the Need for Antepartum Thromboprophylaxis in Pregnant Women With One Prior Episode of Venous Thromboembolism

Pregnant women with a prior history of venous thromboembolism (VTE) are at increased risk of recurrent VTE. Current guidelines assessing the role of prophylaxis in pregnant women with prior VTE are based primarily on expert opinion and the optimal clinical management strategy remains unclear. This multicentre, prospective cohort study aims to test the following hypotheses: 1. Antepartum prophylaxis with fixed-dose low molecular-weight heparin (LMWH) is safe, convenient and associated with an acceptably low risk of recurrent VTE in women with a single prior episode of VTE that was either unprovoked or associated with a minor transient risk factor. (Moderate risk cohort) 2. Withholding antepartum prophylaxis is safe (recurrence risk <1%) in pregnant women with a single prior episode of VTE provoked by a major transient risk factor. (Low risk cohort) All study patients will receive 6 weeks of postpartum prophylaxis.

NCT01357941 Venous Thromboembolism Deep Vein Thrombosis Pulmonary Embolism

MeSH:Pulmonary Embolism Thrombosis Thromboembolism Embolism Venous Thromboembolism Venous Thrombosis

HPO:Deep venous thrombosis Pulmonary embolism Thromboembolism Venous thrombosis

Inclusion Criteria: - Confirmed pregnancy (positive serum or urine) - At least 18 years of age - History of one prior episode of VTE consisting of DVT (diagnosed by compression ultrasonography [CUS] or venography) and/or PE (diagnosed by ventilation-perfusion [V/Q] lung scintigraphy, computed tomographic pulmonary angiography [CTPA], or traditional pulmonary angiography) Exclusion Criteria: - Ongoing need for therapeutic anticoagulation for prevention or treatment of cardioembolic stroke - Known high-risk thrombophilia (specifically antithrombin deficiency, protein S deficiency, protein C deficiency, homozygosity for the factor V Leiden or prothrombin G20210A mutations, antiphospholipid antibody or compound abnormalities) - VTE within 3 months of the current pregnancy - Clinical risk factor for initial episode of VTE, if present, not resolved (excluding pregnancy) - Known contraindication to anticoagulation (including active, uncontrolled bleeding or major bleed within the previous 4 weeks) - For patients with prior unprovoked VTE, contraindication to LMWH (including allergy, HIT, impaired renal function, osteoporosis) - Geographic or social factors precluding follow-up - Inability or unwillingness to provide informed consent Inclusion Criteria: - Confirmed pregnancy (positive serum or urine) - At least 18 years of age - History of one prior episode of VTE consisting of DVT (diagnosed by compression ultrasonography [CUS] or venography) and/or PE (diagnosed by ventilation-perfusion [V/Q] lung scintigraphy, computed tomographic pulmonary angiography [CTPA], or traditional pulmonary angiography) Exclusion Criteria: - Ongoing need for therapeutic anticoagulation for prevention or treatment of cardioembolic stroke - Known high-risk thrombophilia (specifically antithrombin deficiency, protein S deficiency, protein C deficiency, homozygosity for the factor V Leiden or prothrombin G20210A mutations, antiphospholipid antibody or compound abnormalities) - VTE within 3 months of the current pregnancy - Clinical risk factor for initial episode of VTE, if present, not resolved (excluding pregnancy) - Known contraindication to anticoagulation (including active, uncontrolled bleeding or major bleed within the previous 4 weeks) - For patients with prior unprovoked VTE, contraindication to LMWH (including allergy, HIT, impaired renal function, osteoporosis) - Geographic or social factors precluding follow-up - Inability or unwillingness to provide informed consent Venous Thromboembolism Deep Vein Thrombosis Pulmonary Embolism Pulmonary Embolism Thrombosis Thromboembolism Embolism Venous Thromboembolism Venous Thrombosis null --- G20210A ---

Inclusion Criteria: - Confirmed pregnancy (positive serum or urine) - At least 18 years of age - History of one prior episode of VTE consisting of DVT (diagnosed by compression ultrasonography [CUS] or venography) and/or PE (diagnosed by ventilation-perfusion [V/Q] lung scintigraphy, computed tomographic pulmonary angiography [CTPA], or traditional pulmonary angiography) Exclusion Criteria: - Ongoing need for therapeutic anticoagulation for prevention or treatment of cardioembolic stroke - Known high-risk thrombophilia (specifically antithrombin deficiency, protein S deficiency, protein C deficiency, homozygosity for the factor V Leiden or prothrombin G20210A mutations, antiphospholipid antibody or compound abnormalities) - VTE within 3 months of the current pregnancy - Clinical risk factor for initial episode of VTE, if present, not resolved (excluding pregnancy) - Known contraindication to anticoagulation (including active, uncontrolled bleeding or major bleed within the previous 4 weeks) - For patients with prior unprovoked VTE, contraindication to LMWH (including allergy, HIT, impaired renal function, osteoporosis) - Geographic or social factors precluding follow-up - Inability or unwillingness to provide informed consent Inclusion Criteria: - Confirmed pregnancy (positive serum or urine) - At least 18 years of age - History of one prior episode of VTE consisting of DVT (diagnosed by compression ultrasonography [CUS] or venography) and/or PE (diagnosed by ventilation-perfusion [V/Q] lung scintigraphy, computed tomographic pulmonary angiography [CTPA], or traditional pulmonary angiography) Exclusion Criteria: - Ongoing need for therapeutic anticoagulation for prevention or treatment of cardioembolic stroke - Known high-risk thrombophilia (specifically antithrombin deficiency, protein S deficiency, protein C deficiency, homozygosity for the factor V Leiden or prothrombin G20210A mutations, antiphospholipid antibody or compound abnormalities) - VTE within 3 months of the current pregnancy - Clinical risk factor for initial episode of VTE, if present, not resolved (excluding pregnancy) - Known contraindication to anticoagulation (including active, uncontrolled bleeding or major bleed within the previous 4 weeks) - For patients with prior unprovoked VTE, contraindication to LMWH (including allergy, HIT, impaired renal function, osteoporosis) - Geographic or social factors precluding follow-up - Inability or unwillingness to provide informed consent Venous Thromboembolism Deep Vein Thrombosis Pulmonary Embolism Pulmonary Embolism Thrombosis Thromboembolism Embolism Venous Thromboembolism Venous Thrombosis null --- G20210A --- --- G20210A ---

21 Thrombophilic Risk Factors in Preterm and Infants Treated at Ha'Emek Medical Center Between the Years 1990 to 2010

There are several factor that can be related to Neonatal Thrombotic events. Among them hypercoagulability can be the cause of those events. Factor V Leiden (FVL) and Prothrombin mutation are the most common causes of hereditary thrombophilia. The incidence of in the arab population is known to be higher than the incidence in another western populations. The purpose of this study is to review retrospectively the thrombophilic risk factors that were found in a cohort of premature babies and term newborns treated and investigated at the Neonatal Intensive Care Unit and at the Pediatric Hematology Unit.

NCT01443273 Premature Thrombosis Other: Medical Records study

MeSH:Thrombosis

Also the three common genetic factors are analysed including Factor F Leiden (G1691A), Prothrombin Mutation (G20210A) and MTHFR polymorphism (C677T). --- G1691A --- --- G20210A ---

22 Prevalence of Clinical and Laboratory Markers of Hypofibrinolysis in Psychotic Patients

At the Thrombophilia Clinic of the Hospital Federal dos Servidores do Estado do Rio de Janeiro there is a high prevalence of acute psychotic episodes, which allows the investigators to raise the suspicion that the thrombotic tendency or hypofibrinolysis play a role in the onset of the disease. It is striking that most of these patients, after some time on anticoagulants, no longer need to take psychiatric medication.

NCT01487291 Insulin Resistance Thrombophilia Psychosis

MeSH:Thrombophilia Insulin Resistance

HPO:Hypercoagulability Insulin resistance

This study intents to investigate the prevalence of hypofibrinolysis markers, such as PAI-1 4G/5G and 4G/4G, protein S deficiency, antiphospholipid antibodies and prothrombin G20210A, in psychotic patients. --- G20210A ---

23 Effectiveness of Aspirin in Compare With Heparin Plus Aspirin in Recurrent Pregnancy Loss Treatment

This study evaluated the effect of anticoagulant treatment on the live-birth rate in women with a history of at least two continuous unexplained miscarriages or thrombophilia. It also compared two methods of treatment with aspirin and aspirin plus heparin.

NCT01542411 Recurrent Pregnancy Loss

MeSH:Abortion, Habitual

Inclusion Criteria: - unexplained recurrent miscarriage, - women had previous venous or arterial thromboembolism or who were heterozygous or homozygous for mutations for FV Leiden G1691A, prothrombin gene G20210A (FII G20210A), and methyltetrahydrofolate reductase C677T (MTHFR C677T) Exclusion Criteria: - abnormal karyotypes of both partners, - uterine and cervical anatomical disorders on pelvic ultrasonography or hysteroscopy, - abnormal ovaries and abnormal endocrine tests. --- G1691A --- --- G20210A ---

Inclusion Criteria: - unexplained recurrent miscarriage, - women had previous venous or arterial thromboembolism or who were heterozygous or homozygous for mutations for FV Leiden G1691A, prothrombin gene G20210A (FII G20210A), and methyltetrahydrofolate reductase C677T (MTHFR C677T) Exclusion Criteria: - abnormal karyotypes of both partners, - uterine and cervical anatomical disorders on pelvic ultrasonography or hysteroscopy, - abnormal ovaries and abnormal endocrine tests. --- G1691A --- --- G20210A --- --- G20210A ---

24 Randomized Double Blind Placebo-controlled Phase II Trial of Vargatef® (Nintedanib) in Addition to First Line Chemotherapy With Interval Debulking Surgery in Patients With Adenocarcinoma of the Ovary, the Fallopian Tube or Serous Adenocarcinoma of the Peritoneum

Patients with extensive and bulky disease are often those whose initial surgery is delayed after 3 or 4 cycles of neo-adjuvant chemotherapy. In that case, there is, indeed, some concern to administer bevacizumab during the chemotherapy surrounding the interval debulking surgery due to the long half life (14- 21 days) of this monoclonal antibody and the interference of anti angiogenic agents with wound healing. Vargatef® (Nintedanib) might offer a better alternative to bevacizumab in the neo-adjuvant setting. Vargatef® (Nintedanib) has a much shorter half-life of 7 to 19 hours. Preliminary experience in cancer did not show a trend for increased incidence of fistula or bowel perforation. For more details please refer to the investigator drug brochure for Vargatef® (Nintedanib). This trial will compare progression-free survival and surgical complications of 188 patients with FIGO stage IIIC/IV treated in first line with either neo-adjuvant chemotherapy (carboplatin & paclitaxel) and interval debulking surgery or the same treatment + Vargatef® (Nintedanib).

NCT01583322 Ovarian Cancer Drug: vargatef Drug: placebo

MeSH:Ovarian Neoplasms Carcinoma, Ovarian Epithelial

HPO:Ovarian neoplasm

germ cell tumour, malignant mixed mullerian tumour, sex cord-stromal tumour) of the ovary, the fallopian tube or peritoneum or borderline tumour of the ovary (tumour of low malignant potential), - Non-healing wound, ulcer (intestinal tract, skin) or bone fracture, - Clinical symptoms or signs of gastrointestinal obstruction, - History of major thromboembolic event, defined as: - Pulmonary embolism (PE) within 6 months prior to enrolment, - Recurrent pulmonary embolism (history of at least 2 events), - History of at least 2 unprovoked (without a transient or reversible risk factor) events of proximal deep venous thrombosis, - Prior thrombosis or thromboembolic event in the presence of an inherited coagulopathy (including deficiency of antithrombin, deficiency of protein C or protein S, Factor V Leiden mutation, Prothrombin G20210A mutation), - Patients with perioperative thrombosis including proximal deep vein thrombosis (DVT) or thrombosis of visceral vessels not associated with pulmonary embolism may be included in the trial if stable therapeutic anticoagulation is documented, - Known inherited or acquired bleeding disorder, - Significant cardiovascular diseases, including: - Hypertension not controlled by medical therapy, - Unstable angina within the past 6 months, - History of myocardial infarction within the past 6 months, - Congestive heart failure > NYHA II, - Clinically relevant cardiac arrhythmia - Peripheral vascular disease Fontaine stage ≥3, - Clinically relevant pericardial effusion (e.g. --- G20210A ---

25 Fixed-dose vs. Phenotype-based PrAsugrel Dose to MATCH Therapeutic Zone in Asians With Acute Coronary Syndrome

The purpose of this study is to determine whether the fixed-dose (prasugrel 10 mg/d vs. 5 mg/d) vs. phenotype (platlet function test by VerifyNow P2Y12 assay)-based prasugrel dose adjustment can match therapeutic zone of platelet reactivity in PCI-treated Asians with acute coronary syndrome

NCT01951001 Acute Coronary Syndrome Platelet Thrombus Bleeding Drug: Prasugrel

MeSH:Acute Coronary Syndrome Syndrome

The convincing associations of arterial thrombosis to coagulation system and inflammation have been repeatedly demonstrated in multiple clinical trials: fibrinogen, factor V Leiden (G1691A) and prothrombin G20210A gene mutations, high-sensitivity C-reactive protein (CRP) and so on. --- G1691A --- --- G20210A ---

26 A Randomized, Global, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Once-daily Oral Avatrombopag for the Treatment of Adults With Thrombocytopenia Associated With Liver Disease Prior to an Elective Procedure

This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel group study using avatrombopag to treat adults with thrombocytopenia associated with liver disease. The study will evaluate avatrombopag in the treatment of thrombocytopenia associated with liver disease prior to an elective procedure to reduce the need for platelet transfusions or any rescue procedure for bleeding due to procedural and post-procedural bleeding complications. Participants will be enrolled into 2 cohorts according to mean baseline platelet count and, within each baseline platelet count cohort will be further stratified by risk of bleeding associated with the elective procedure (low, moderate, or high) and hepatocellular carcinoma (HCC) status (Yes or No).

NCT01972529 Thrombocytopenia Associated With Liver Disease Drug: avatrombopag (lower baseline platelet count) Drug: placebo (lower baseline platelet count) Drug: avatrombopag (higher baseline platelet count) Drug: placebo (higher baseline platelet count)

MeSH:Liver Diseases Thrombocytopenia

HPO:Abnormality of the liver Decreased liver function Elevated hepatic transaminase Thrombocytopenia

Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency, etc.) 18. Participants with a history of significant cardiovascular disease (eg, congestive heart failure New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events [eg, atrial fibrillation], coronary artery stent placement, angioplasty, and coronary artery bypass grafting) 19. --- G20210A ---

27 A Randomized, Global, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Once-daily Oral Avatrombopag for the Treatment of Adults With Thrombocytopenia Associated With Liver Disease Prior to an Elective Procedure

This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel group study using avatrombopag to treat adults with thrombocytopenia associated with liver disease. The study will evaluate avatrombopag in the treatment of thrombocytopenia associated with liver disease prior to an elective procedure to reduce the need for platelet transfusions or any rescue procedure for bleeding due to procedural and post-procedural bleeding complications. Participants will be enrolled into 2 cohorts according to mean baseline platelet count and, within each baseline platelet count cohort will be further stratified by risk of bleeding associated with the elective procedure (low, moderate, or high) and hepatocellular carcinoma (HCC) status (Yes or No).

NCT01976104 Thrombocytopenia Associated With Liver Disease Drug: avatrombopag (lower baseline platelet count) Drug: placebo (lower baseline platelet count) Drug: avatrombopag (higher baseline platelet count) Drug: placebo (higher baseline platelet count)

MeSH:Liver Diseases Thrombocytopenia

HPO:Abnormality of the liver Decreased liver function Elevated hepatic transaminase Thrombocytopenia

Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency, etc.) 18. Participants with a history of significant cardiovascular disease (eg, congestive heart failure New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events [eg, atrial fibrillation], coronary artery stent placement, angioplasty, and coronary artery bypass grafting) 19. --- G20210A ---

28 Pilot Study of Post-thrombotic Syndrome & Predictors of Recurrence in Cancer Patients With Catheter-related Thrombosis

The goal of the pilot study is to determine if a multicenter prospective cohort study of cancer patients with blood clots associated with catheters is feasible. Cancer patients with catheter-related thrombosis treated with one month of anticoagulation will be evaluated for for post-thrombotic syndrome. Laboratory biomarkers will be evaluated as predictors of recurrent thrombosis.

NCT01999179 Venous Thrombosis Neoplasms Drug: Heparin, Low-Molecular-Weight, or direct oral anticoagulants

MeSH:Thrombosis Venous Thrombosis Postthrombotic Syndrome Postphlebitic Syndrome Recurrence

HPO:Deep venous thrombosis Venous thrombosis

- >18 years of age - Platelet count >50,000 - Creatinine clearance >30 ml/min - Ability to provide informed consent Exclusion Criteria: - Underlying medical condition or chemotherapy requiring long-term anticoagulation - Known underlying higher risk thrombophilias including antiphospholipid antibody syndrome, antithrombin, protein C or protein S deficiencies, or homozygosity or compound heterozygosity for prothrombin G20210A or Factor V R506Q mutations. --- G20210A ---

29 Evaluation of FDOPA-PET/MRI in Pediatric Patients With CNS Tumors, A Feasibility Study

To determine if FDOPA-PET/MRI imaging can predict response to treatment of bevacizumab.

NCT01999270 Astrocytoma, Oligoastrocytoma, Mixed Ganglioneuroma Glioma Ganglioglioma Glioblastoma Multiforme Glioma Drug: Irinotecan Drug: Bevacizumab Device: FDOPA-PET/MRI imaging

MeSH:Glioblastoma Glioma Astrocytoma Ganglioglioma Ganglioneuroma

HPO:Astrocytoma Ganglioneuroma Glioblastoma multiforme Glioma Subependymal giant-cell astrocytoma

- Patient must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia, or antiphospholipid antibody syndrome). --- G20210A ---

30 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once-daily Oral Avatrombopag in Japanese Subjects With Chronic Liver Disease and Thrombocytopenia

This is a phase 2, randomized, double-blind, placebo-controlled, parallel group study using avatrombopag for Japanese subjects with thrombocytopenia associated with chronic liver disease. This study will assess the effect of avatrombopag on platelet counts in Japanese subjects. Subjects will be enrolled into 2 cohorts according to the mean platelet count measured at Screening and Baseline. Within the lower baseline platelet count cohort (less than 40 x 10^9/L), subjects will be randomized in a 1:1:1:3 ratio to receive placebo, 20 mg avatrombopag, 40 mg avatrombopag, or 60 mg avatrombopag for 5 days. Within the higher baseline platelet count cohort (from 40 to less than 50 x 10^9/L), subjects will be randomized in a 2:1:2 ratio to receive placebo, 20 mg avatrombopag, or 40 mg avatrombopag for 5 days.

NCT02227693 Thrombocytopenia Associated With Chronic Liver Dise Thrombocytopenia Associated With Chronic Liver Disease Drug: avatrombopag Drug: Placebo

MeSH:Liver Diseases Thrombocytopenia

HPO:Abnormality of the liver Decreased liver function Elevated hepatic transaminase Thrombocytopenia

Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency etc.) 17. --- G20210A ---

31 A Proposal of a Prospective Study on Prevention of Pregnancy Loss in Women Carrying Inherited Thrombophilia

The occurrence of a spontaneous fetal loss (FL) is a rather frequent event: it has been estimated that up to 15% of pregnancies result in a fetal loss. However, recurrent events, defined as >2 or >3 loss, depending on the guidelines used (American College of Obstetricians and Gynecologists or Royal College of Obstetricians Gynaecologists guidelines), occur in 1 % of all pregnancies and it is noteworthy that Recurrent Fetal Loss ( RFL) in about 30-40% of cases remain unexplained after standard gynaecological, hormonal and karyotype investigations. Furthermore, it is important to consider that chromosomal abnormalities are responsible for at least 60% of FL in the first trimester, thus an abnormal karyotype in the fetus should be excluded prior to consider testing women for genetic susceptibility to placental vascular complications (inherited thrombophilia). Common inherited conditions, the factor V Leiden (FV) and the factor II G20210A (FII) mutations have been recognized as risk factors for FL. The efficacy of treatment with antithrombotic drugs during pregnancy in women with a history of RFL/ Intra Uterine Fetal Death (IUFD) and thrombophilia is still debated, due to scarcity of available data. Italian guidelines suggest the use of Low-Molecular-Weight Heparin (LMWH) in women with FV or FII mutations and previous otherwise unexplained obstetric complications, while guidelines released by RCOG suggest that heparin therapy during pregnancy may improve the live birth rate in women with second trimester loss associated with inherited thrombophilias. Hence, the idea to propose this prospective observational study comparing clinical data and outcomes in women with common inherited thrombophilias and in women without. During this study the investigators will collect and evaluate clinical data from examinations and visits by patients, eligible for the study as carriers of thrombophilic defects. This observation will begin before pregnancy and continue until the puerperium, allowing us to study all possible factors influencing these conditions. The study will add knowledge for improving feto-maternal prognosis and preventing spontaneous and recurrent FL. Plan of the study: multicenter observational study

NCT02385461 Pregnancy Complications Drug: Low Molecular Weight Heparins (LMWHs)

MeSH:Pregnancy Complications Thrombophilia

HPO:Hypercoagulability

Common inherited conditions, the factor V Leiden (FV) and the factor II G20210A (FII) mutations have been recognized as risk factors for FL. --- G20210A ---

32 Clinical Investigation to Evaluate the Haemonetics POLFA Modified Sample Needle Assembly With Vacuum Tube Holder

This study evaluates whether whole blood transferred through the new POLFA needle assembly meets supernatant hemoglobin acceptability standards.

NCT02476851 Transmission, Blood, Recipient/Donor Device: POLFA (Needle Assembly) Device: Kawasumi (Needle Assembly)

- Study donors must not have experienced any of the following: Physical trauma consistent with associated coagulopathy within the last 30 days, Surgery within the last 30 days, Known history of hypercoagulopathy (i.e., Factor V Leiden, Prothrombin G20210A, idiopathic venous thrombotic events, etc.). --- G20210A ---

33 Thromboprophylaxis in Pregnant Women in Hospital: A Prospective Clinical Trial

Hospitalization in pregnancy and childbirth greatly increases the thromboembolic risk of these patients. The application of a protocol for assessing the risk of VTE reduces mortality and morbidity of these phenomena.

NCT02600260 Thrombophilia Associated With Pregnancy Perioperative/Postoperative Complications Venous Thrombosis Pulmonary Embolism Other Specified Risk Factors in Pregnancy Deep Vein Thrombosis Drug: Enoxaparin Other: No intervention

MeSH:Pulmonary Embolism Thrombosis Embolism Venous Thrombosis Thrombophilia Postoperative Complications

HPO:Deep venous thrombosis Hypercoagulability Pulmonary embolism Venous thrombosis

Risk score description: score 3 - previous thrombosis/thromboembolism, homozygous mutations, combined thrombophilia risk factors, antiphospholipid syndrome, cancer(stomach, pancreas, lung), inflammatory conditions, lupus, sickle cell disease, nephrotic syndrome, heart disease; Score 2 - Protein C deficiency, Protein S deficiency, heterozygous F5 Leiden, heterozygous F2 G20210A mutation, cancer(last 6 months), chemotherapy(last 6m), immobility, bed rest >4d prior to C-section, current serious infections, BMI≥40 kg/m2 , age≥40y, lung disease(cyanosis), postpartum hemorrhage >1L; Score 1 - age ≥ 35 and ≤39 y, parity ≥3, multiple pregnancy, hyperemesis, gross varicose veins, smoker ≥20, surgical procedure. --- G20210A ---

34 Risk Factors for Variceal Bleeding in Egyptian Patients With Non-Cirrhotic Portal Hypertension

Background & Aims: Non-cirrhotic portal hypertension (NCPH) represents a relatively infrequent group of conditions. This work aimed at determining causes of NCPH and evaluating the role of some clinical, laboratory, imaging and endoscopic parameters in prediction of variceal bleeding in an Egyptian cohort with NCPH. Methods: Sixty patients with non-cirrhotic portal hypertension and oesophageal varices were included. All underwent complete clinical evaluation, laboratory investigations, Color Doppler ultrasonography, platelet count/spleen diameter (mm) ratio and upper gastrointestinal endoscopy. Patients were classified into two groups according to variceal bleeding: (1) Group I: twenty six patients with history of bleeding or had an attack of bleeding during one year follow-up; and (2) Group II: thirty four patients without bleeding.

NCT02635815 Portal Hypertension Procedure: Upper gastrointestinal endoscopy

MeSH:Hypertension, Portal Hypertension

HPO:Hypertension Portal hypertension

It was done only for patients with Budd-Chiari syndrome and extrahepatic portal vein thrombosis: anticardiolipin antibodies, lupus anticoagulant, antinuclear antibodies, protein C, S, antithrombin III, factor V Leiden G1691A mutation, prothrombin gene G20210A mutation, methylene tetrahydrofolate reductase C677T mutation by PCR, Janus tyrosine kinase-2 (JAK II) V617F mutation by PCR (to exclude myeloproliferative disorders) and flow cytometry for CD55 and CD59 (to exclude paroxysmal nocturnal hemoglobinuria); (4) Abdominal ultrasonography: for liver size, echogenicity, spleen size, portal vein diameter and ascites; (5) Color Doppler ultrasonographic study: was done in the morning after an overnight fasting using a color Doppler unit with a 3.5 MHz convex probe for confirmation of portal vein (PV) patency and diameter, mean PV flow velocity (mean PVV) (cm/sec), PV direction of flow, splenic vein patency and diameter, presence of portosystemic collaterals and patency of hepatic veins; (6) Platelet count/spleen diameter ratio: calculated as: platelet count/ maximum spleen bipolar diameter by ultrasound in mm; (7) Ultrasonography guided liver biopsy: for diagnosis of NCPH and exclusion of cirrhotic portal hypertension; and (8) Upper gastrointestinal endoscopy using the Pentax video endoscope EG 3440. --- G1691A --- --- G20210A ---

35 A Toll-like Receptor Agonist as an Adjuvant to Tumor Associated Antigens (TAA) Mixed With Montanide ISA-51 VG With Bevacizumab for Patients With Recurrent Glioblastoma

This is a phase II study to determine the immunogenicity and efficacy of a vaccine composed of tumor associated long synthetic peptides mixed with Montanide ISA-51 VG administered with polyinosinic-polycytidylic acid - poly-L-lysine carboxymethylcellulose (Poly-ICLC) and bevacizumab in adults with recurrent glioblastoma.

NCT02754362 Glioblastoma Glioma Drug: Bevacizumab Biological: Peptide Vaccine Drug: Poly-ICLC as immune adjuvant Drug: Keyhole limpet hemocyanin (KLH)

MeSH:Glioblastoma

HPO:Glioblastoma multiforme

- Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome). --- G20210A ---

36 A Phase 1 Multi-Center, Dose-Escalation Study of Vonapanitase Administered Percutaneously to the Superficial Femoral or Popliteal Artery in Patients With Peripheral Artery Disease

The research study is designed to assess the technical feasibility and safety of percutaneous administration of vonapanitase to the superficial femoral or popliteal artery in patients with PAD.

NCT02953496 Peripheral Artery Disease Drug: vonapanitase

MeSH:Peripheral Arterial Disease

HPO:Peripheral arterial stenosis

7. Known hypercoagulable state (e.g., protein C deficiency, factor V Leiden mutation, prothrombin G20210A mutation). --- G20210A ---

37 A Phase 1, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study of Vonapanitase Administered Following Angioplasty of a Distal Popliteal, Tibial or Peroneal Artery in Patients With Peripheral Artery Disease

The research study is designed to assess the technical feasibility and safety of a perivascular injection of vonapanitase delivered via micro-infusion catheter to the distal popliteal, tibial or peroneal arteries immediately following successful angioplasty.

NCT02956993 Perip Peripheral Artery Disease Drug: vonapanitase Drug: Placebo

MeSH:Peripheral Arterial Disease

HPO:Peripheral arterial stenosis

6. Known hypercoagulable state (e.g., protein C deficiency, factor V Leiden, prothrombin G20210A mutation). --- G20210A ---

38 Intralipid Related Effect on NKcells in Patients With Unexplained Recurrent Spontaneous Abortions

Evaluating the effect of intralipid on the natural killer cells

NCT03132779 Recurrent Miscarriage Drug: Intralipid

MeSH:Abortion, Spontaneous Abortion, Habitual

HPO:Spontaneous abortion

Exclusion Criteria: - Any other diseases causing miscarriage as autoimmune (lupus erythematosus or antiphospholipid antibodies syndrome )or endocrinopathy (diabetes mellitus, thyroid disorders and hyperprolactinaemia)or thrombophilia (factor v leiden mutation, protein c or s deficiency, prothrombin G20210A mutation, antithrombin III deficiency ) or abnormal karyotyping to one or both of parents or previous history of hormonal contraception or intrauterine device usage at last 3 months or any contraindications for intralipid usage. --- G20210A ---

39 Downstream Molecular Signals of P2Y12 Receptors in Hyporeactive Patients Under Clopidogrel Treatment (A Possible Mechanism of HOTPR:High On- Treatment Platelet Reactivity)

The investigators designed the following experiment to observe the pattern of administration in vitro, which can be completely excluded liver enzyme cytochrome P450 metabolism under the influence and observe the relevant P2Y12 receptor downstream signal changes, hope in the above experiments, that the human body directly for the difference between the existence of drug reactions exist.

NCT03190005 Stable Angina Drug: clopidogrel Drug: Placebos

MeSH:Angina, Stable

The investigators ran a previous related plan within 2014 under the medical study project budget of the Taipei City hospital, which named "platelet reactivity as a post-percutaneous coronary stent implantation antiplatelet adjust the reference", it has been figured that responsibility under the P2Y12 receptor inhibitors were significantly different between the taiwanese and Caucasians (taiwanese revealed clopidogrel lower responsive, but stronger reaction to ticagrelor), although "low" response to clopidogrel between taiwanese (In fact, according to our experiments, 30 days after medication, the rate of HOTPR-High On- Treatment Platelet Reactivity; namely PRU≥208, the taiwanese and Caucasians are very close to each), but it has relative lower subacute stent thrombosis rate than the Caucasian at 30 days(This reaction is also known as the "Asian paradox" ), according to literature known abroad because of the high prevalence of CYP2C19 point gene deletion rate among the Asians (compare with Caucasians: ~ 65% vs ~ 30%); there also suggested other possible explanations: Caucasian factor V Leiden (G1691A) and prothrombin (G20210A) a higher proportion of mutations, on hemostatic factors (fibrinogen, d-dimer, and factor VIII) and plasma endothelial activation markers (such as von Willebrand factor, intercellular adhesion molecule 1, and E-selectin) existed differences between the races; in addition, a number of different indicators of inflammation, such as CRP. --- G1691A --- --- G20210A ---

40 Risk of Venous Thromboembolism in First Degree Relatives of Women With or Without Venous Thromboembolism During Hormonal Exposure

Young women have an increased risk of venous thromboembolism (VTE) during hormonale exposure (estrogen-containing pill or pregnancy). In order to detect women at higher risk of VTE during hormonal exposure, thrombophilia testing is often performed in order to adapt contraception methods and/or to increases thromboprophylaxy during pregnancy. However, such practice is probably not accurate nor discriminent. Indeed, there are evidence that the impact of the familial history of VTE might be stronger than that of detectable inherited thrombophilia. The "FIT-H" study is a cross-sectional study comparing the prevalence of previous venous thromboembolism in first-degree relatives of women (propositi) who had a first episode of venous thromboembolism in association with hormonal exposure with the prevalence of previous venous thromboembolism in first-degree relatives of women who did not have venous thromboembolism during a similar hormonal exposure. The primary objective is to determine the association between the presence or the absence of VTE in young women during hormonal exposure and the presence or the absence of a previous episode of VTE in their first-degree relatives. Secondary objective is to determine the impact of associated inherited thrombophilia on the risk of VTE in first-degree relatives.

NCT03206372 Venous Thromboembolic Disease Other: Case group Other: Control group

MeSH:Thromboembolism Venous Thromboembolism

HPO:Thromboembolism

- Secondary objectives: - To determine if this there is an influence of a detectable inherited minor thrombophilia (factor V Leiden, G20210A prothrombin variant) on the risk of VTE in first-degree relatives - To determine if this there is an influence of a detectable inherited major thrombophilia (protein, S or antithrombin deficiency) on the risk of VTE in first-degree relatives - To determine the impact of the clinical characteristics of VTE in their first-degree relatives (age, dead or alive at the time of inclusion) - To determine the impact of clinical characteristic of VTE in the propositus (age, PE vs DVT, severity of VTE, type of hormonal exposure) on the risk of VTE in the first-degree relatives. --- G20210A ---

41 The Role of Prothrombin Gene and Methylenetetrahydrofolate Reductase(MTHFR) Gene Polymorphisms as Risk Factors for Recurrent Miscarriage

Recurrent miscarriage is a pregnancy loss before 20 weeks of gestation. The recurrent pregnancy loss(RPL) usually occurring in the first trimester of gestation and its rate is quite high (15-20% even in full reproductive period) . In 2012, the American Society for Reproductive Medicine Practice Committee issued a statement that defined recurrent pregnancy loss as a disease distinct from infertility defined by two or more failed consecutive pregnancies.approximately 40% of couples will have an etiology identified that could be associated with their loss.

NCT03209063 Recurrent Miscarriage Diagnostic Test: polymerase chain reaction

MeSH:Abortion, Spontaneous Abortion, Habitual

HPO:Spontaneous abortion

40% of couples will have an etiology identified that could be associated with their loss.Thrombophilia is the tendency to develop thromboses due to inherited defects in the coagulation system.Thrombophilia was identified as a major cause of RPL,Because pregnancy is a hypercoagulable state, thromboembolism is the leading cause of antepartum and postpartum maternal mortality .The four most common genetic markers for thrombophilia are; prothrombin gene mutation(FII, G20210A), methylene tetra hydrofolate reductase mutations (MTHFR ,C677T and A1298C), factor V Leiden (FVL, G1691A) , and plasminogen activator inhibitor 1 (PAI-1) . --- G20210A ---

Prothrombin G20210A refers to a human gene mutation that increases the risk of blood clots . --- G20210A ---

Study was conducted to evaluate the frequency of PT20210 among healthy Egyptians, (1.06%) had PT20210 G-A mutation.The variant causes elevated plasma prothrombin levels (hyperprothrombinemia), Prothrombin is the precursor to thrombin, which plays a key role in causing blood to clot (blood coagulation).Prothrombin G20210A can thus contribute to a state of hypercoagulability . --- G20210A ---

42 STUDY OF THE ADAMTS-13 LEVEL AS PREDICTIVE BIOMARKER FOR DEVELOPMENT OF PORTAL VEIN THROMBOSIS IN LIVER CIRRHOSIS

Patients with cirrhosis of viral etiology (HCV/HBV); Patients with cirrhosis of any other etiology (alcohol, idiopatic, autoimmune). Planned Number of cirrhotic subjects 200 patients Inclusion Criteria Subjects (18 yr old) with liver cirrhosis of any etiology, Exclusion Criteria All patients should not have hepatocellular carcinoma or other malignant tumors, they should not be treated with anticoagulant / antiplatelet agents, not affected by PVT already diagnosed and not suffering from congenital coagulation disorders (haemophilia A / B, von disease Willebrand, another congenital deficiency of coagulation factors) or severe thrombocytopenia (<30,000 Plt / μL). Subject has participated in another clinical study within 30 days prior to study enrollment or is scheduled to participate in another clinical study on cirrhosis Primary Objective To describe the prospective modification of ADAMTS-13 level and other coagulation variables (e.g. FVIII, VWF:Ag/VWF:act) in cirrhotic patients during 18 months from the enrolment and to verify their predictive role as biomarker of development of portal vein thrombosis (PVT) Secondary Objectives To describe prospectively the modification of ADAMTS-13 level as a function of the etiology of cirrhosis Statistical analysis The total duration of the study will be of 12 months. The sample size of 200 subjects will be selected as a feasible number of patients to be recruited in a period of six months. The patients will be consecutively enrolled and followed for 18 months. As a result, in a follow up period of 18 months about 20-25 cases of PVT are expected. Continuous variables will be expressed as means ± standard deviations. In addition to descriptive statistics (location parameters), univariate analysis will be performed on each parameter and development of PVT during the follow up period. In previous observational studies both 1) a reduced PV flow [prospectively] and 2) a reduction of ADAMTS-13 are significantly associated with PVT. These associations will be investigated prospectively and analyzed simultaneously by a multivariate analysis and ROC curve to establish the sensitivity and specificity of these parameters as predictors of PVT development. Analyses will be performed using available data

NCT03322696 C23.550.355 C14.907.355.830.925 C15.378.140.855.925

MeSH:Liver Cirrhosis Thrombosis Venous Thrombosis

HPO:Cirrhosis Deep venous thrombosis Hepatic fibrosis Venous thrombosis

FV Leiden R506Q and prothrombin G20210A genotyping of these polymorphisms was performed by using commercial kits based on PCR-RT-based method (from EliTechGroup S.p.A., Torino, Italy) on an automatic instrument (Model 7300, Applied Biosystem, Foster City, CA, USA). --- R506Q --- --- G20210A ---

43 Prediction of Recurrent Pregnancy Loss by a New Thrombophilia Based Genetic Risk Score

Recurrent pregnancy loss (RPL) is a clinical problem affecting 1-5% of couples of reproductive age. The contribution of thrombophilia to RPL is disputed. This controversy is partly due to low sensitivity of the genetic variants currently used to evaluate hereditary thrombophilia: the Leiden mutation (identified as rs6025) in the coagulation factor 5 (F5L) gene and mutation G20210A (identified as rs1799963) in the prothrombin (PT) gene. Our objective was to determine whether a wider algorithm that includes clinic and genetic variants associated with thrombophilia could be more useful in the prediction for RPL than FVL and PT alone.

NCT03336463 Miscarriage, Recurrent

MeSH:Abortion, Spontaneous Abortion, Habitual Thrombophilia

HPO:Hypercoagulability Spontaneous abortion

This controversy is partly due to low sensitivity of the genetic variants currently used to evaluate hereditary thrombophilia: the Leiden mutation (identified as rs6025) in the coagulation factor 5 (F5L) gene and mutation G20210A (identified as rs1799963) in the prothrombin (PT) gene. --- G20210A ---

This study hypothesize that the use of the Thrombo inCode® in the screening for hereditary thrombophilia in patients with recurrent pregnancy loss can improve the diagnostic sensitivity and predictive capacity of the routine genetic panel, based on FVL and G20210A PT. --- G20210A ---

The results produced from a single genetic analysis will allow comparison to the centres' routine protocol (FV Leiden and G20210A PT) with the complete Thrombo inCode® panel, that also includes the previously-mentioned classical variants. --- G20210A ---

44 Influence of ABO Blood Group on the Risk of Complications in Alcoholic or Viral C Cirrhosis? Analysis From Two French Prospectives National Cohorts CIRRAL and CIRVIR of Patients With Alcoholic or Viral Cirrhosis Child Pugh A

The non-O blood group is a risk factor of deep vein thrombosis and recurrence of thromboembolic events, especially when associated with Factor 5 Leiden or prothrombin G20210A mutations. A recent study suggests that non-O blood group may promote portal vein thrombosis in non cirrhotic patients. In addition, in general population and chronic hepatitis C, non-O blood group combined with one or the other of the above genetic abnormalities is associated with an increased risk of liver fibrosis and accelerated fibrogenesis. The suspected mechanism could be an increased procoagulant factor VIII and an increased Willebrand plasma level, due to a low ADAMTS 13 activity, the result of which is an hypercoagulable state and a microthrombotic process. In cirrhotic patients procoagulant factors and ADAMTS 13 which are respectively increased and decreased, have be shown to be prognostic markers of hepatocellular function and portal hypertension. It has been hypothesized that the hypercoagulable state and the microthrombotic process could contribute to the worsening of the disease and enoxaparin has been shown to positively modify the prognosis of cirrhosis. The role of non-O blood group in decompensation of cirrhosis and occurrence of complications including non-tumor portal vein thrombosis has never been studied. The investigators plan a longitudinal observational study to determine the incidence of complications in alcoholic and viral cirrhosis in case of non-O blood group compared to O blood group. The aim of this study is to determine whether ABO blood group may promote complications in alcoholic or viral cirrhosis. This is an ancillary study of two national cohorts assessing natural history and hepatocellular carcinoma risk factors in alcoholic (CIRRAL) and viral (CIRVIR) cirrhosis.

NCT03342170 Alcoholic or Viral C Compensated Cirrhosis Genetic: G20210A prothrombin gene mutation and Factor 5 Leiden mutation

MeSH:Liver Cirrhosis Fibrosis

HPO:Cirrhosis Hepatic fibrosis

The non-O blood group is a risk factor of deep vein thrombosis and recurrence of thromboembolic events, especially when associated with Factor 5 Leiden or prothrombin G20210A mutations. --- G20210A ---

45 Dental Health in Recurrent Miscarriage

Oral infections can trigger the production of pro-inflammatory mediators that may be risk factors for miscarriage. The investigators investigated whether oral health care patterns that may promote or alleviate oral inflammation were associated with the history of miscarriage in Turkish women.

NCT03577314 Oral Health Miscarriage Other: miscarriage

MeSH:Abortion, Spontaneous Abortion, Habitual

HPO:Spontaneous abortion

At least 8 weeks after termination of pregnancy, karyotype analysis of both couples and thrombophilia panel ( Factor V Leiden, prothrombin gene mutation G20210A, protein S/Protein C/antithrombin deficiency and MTHFR mutations) in the study group will be requested.. Dental Examination. --- G20210A ---

46 APIDULCIS: Extended Anticoagulation With Low-dose Apixaban After a Standard Course Anticoagulation in Patients With a First Venous Thromboembolism Who Have Positive D-dimer

The study aims at optimizing the long-term and extended management of patients with a first episode of venous thromboembolism (proximal deep vein thrombosis with or without pulmonary embolism) (VTE). Patients at high risk of recurrence (with altered D-dimer test), who had received anticoagulation (whatever the drug used) for 12-15 months after the first episode of thrombosis, will be treated with Apixaban 2,5 mg x 2 for 18 months as extended treatment. Patients at low risk, with normal D-dimer test, will stop anticoagulation definitely.

NCT03678506 Venous Thromboembolism Anticoagulants Drug: Apixaban

MeSH:Thromboembolism Venous Thromboembolism

HPO:Thromboembolism

inflammatory bowel disease) - Known serious thrombophilic alterations: - deficiencies of natural anticoagulants (Antithrombin, Protein C, Protein S) - homozygosity for Factor V Leiden or Factor II G20210A mutations - double heterozygosity - Presence of antiphospholipid syndrome - Presence of vein cava filter - Concomitant conditions (such as atrial fibrillation) requiring indefinite anticoagulation - Severe cardio-respiratory insufficiency (NYHA 3 or 4) - Any absolute contraindications to anticoagulation treatment - Any other contraindications to Apixaban as per local SmPC - Life expectancy shorter than 1 year - Refuse interruption of anticoagulation to perform serial D-dimer assessment - Geographically inaccessible location - Inability or refusal to give consent Inclusion Criteria: - First unprovoked Venous Thromboembolic Event - Venous Thromboembolic events associated with one or more risk factors that are no longer present - Age older than 18 or younger than 75 years - Capacity to give written informed consent Exclusion Criteria: - A) Exclusion criteria regarding the index event - Events usually associated with low risk of recurrence - Deep vein thrombosis/ Pulmonary embolism occurred within 3 months from major surgery or major trauma - Isolated Distal deep vein thrombosis (thrombosis of calf veins) - Events associated with a very high risk of recurrence or occurrence of life-threatening recurrent events - Pulmonary Embolism episode with shock or life-threatening - Isolated pulmonary embolism with a systolic pulmonary artery pressure > 60 mmHg at presentation - Deep vein thrombosis/ Pulmonary embolism associated with active cancer, antiphospholipid syndrome or long-standing medical illnesses - More than one idiopathic event - Index venous thromboembolic event in different sites than deep veins of the lower limbs or pulmonary arteries B) Exclusion criteria present at the moment of patients' screening: - Age younger than 18 or older than 75 years - More documented unprovoked venous thromboembolic episodes - Pregnancy or puerperium - Severe post-thrombotic syndrome (≥ 15 points at the Villalta score) - Solid neoplasia or blood disease in active phase or requiring chemotherapy/radiotherapy - All the clinical conditions requiring prolonged treatment with Low Molecular Weight Heparin - Presence of overt, active chronic diseases (i.e. --- G20210A ---

inflammatory bowel disease) - Known serious thrombophilic alterations: - deficiencies of natural anticoagulants (Antithrombin, Protein C, Protein S) - homozygosity for Factor V Leiden or Factor II G20210A mutations - double heterozygosity - Presence of antiphospholipid syndrome - Presence of vein cava filter - Concomitant conditions (such as atrial fibrillation) requiring indefinite anticoagulation - Severe cardio-respiratory insufficiency (NYHA 3 or 4) - Any absolute contraindications to anticoagulation treatment - Any other contraindications to Apixaban as per local SmPC - Life expectancy shorter than 1 year - Refuse interruption of anticoagulation to perform serial D-dimer assessment - Geographically inaccessible location - Inability or refusal to give consent Venous Thromboembolism Anticoagulants Thromboembolism Venous Thromboembolism This prospective cohort study aims to assess the efficacy and safety of a management procedure to decide on giving or not an extended anticoagulation (administering apixaban 2 2.5 mg twice daily ) to outpatients with a single episode of proximal deep vein thrombosis of the lower limbs and/or pulmonary embolism who had received 12-15 months of anticoagulation (whatever the anticoagulant drug used). --- G20210A ---

47 Phase I Study Evaluating Safety and Feasibility of Hematopoietic Stem Cell Gene Transfer That Targets Factor VIII Delivery From Platelets for Patients With Hemophilia A

This is a Phase I study. This research study is being conducted to find new ways to treat severe hemophilia A. This study is a gene therapy study. Gene therapy is an experimental way to introduce, into a person's cells, specific genetic material. A gene can be delivered/introduced into a cell using a carrier known as a "vector." In this study, a virus (lentivirus), the "vector", is used to introduce or deliver a gene that creates and stores a protein Factor VIII (FVIII) in your platelets. These platelets are made from stem cells (mother cells for your bone marrow) that are removed from your blood by a procedure called apheresis. This research study will take some of the patient's own stem cells, from the apheresis procedure, and genetically modify them using the vector in order to make them produce FVIII in platelets that arise from the stem cells. They will then give the genetically modified stem cells back to the patient so that they can possibly create platelets that produce and store Factor VIII on their own.

NCT03818763 Hemophilia A Biological: Auto CD34+PBSC, transduced with a lentiviral vector encoding the B domain deleted from of human coagulation factor VIII

MeSH:Hemophilia A

HPO:Reduced factor VIII activity

Those with a known co-existing clinically significant thrombophilic disorder, or as determined by the presence of any of the below identified on screening laboratory assessments: - FV Leiden - Protein S deficiency - Protein C deficiency - Prothrombin mutation (G20210A) - D-dimer >3 x the upper limit of normal (ULN) at Screening All known patients with the above and any patient with a personal or significant family history of thrombotic events (DVT, PE, arterial clots) as deemed by the principal investigator will be screened for the above disorders. --- G20210A ---

48 A Phase I, Randomized, Double-blind, Placebo-Controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MG1113 in Healthy Subjects and Hemophilia Patients

The purpose of this study is to assess the safety and tolerability of MG1113 in the single ascending dose study (IV injection or SC injection) in healthy subjects and hemophiia patients.

NCT03855696 Hemophilia Biological: MG1113 Other: Placebo of MG1113

MeSH:Hemophilia A

HPO:Reduced factor VIII activity

Any of the following results from laboratory tests: 1) AST (sGOT) or ALT (sGPT) >2 x UNL 2) Hb < 9.0 g/dL 3) Absolute Neutrophil Count < 1500 mm2 4) Platelet count < 100 x 103 mm2 5) aPTT, PT > 1.5 x UNL 6) Have hepatitis B (HBsAg positive) or C (anti-HCV positive), or have positive HIV test result 7) Creatinine clearance ≤80 mL/min (calculated by the Cockcroft-Gault formula) 7. Have a family history or be considered to be at risk of thromboembolic events, or have the following test results: 1) Antithrombin level ≤LNL 2) Protein C or S activity ≤LNL 3) Factor V Leiden mutation 4) Prothrombin G20210A mutation 8. Used ethical drugs including prescription drugs within 14 days of investigational product administration 9. Used drugs (over-the-counter drugs, herbal medicines, and nutritional agents and vitamins for the purpose of same efficacy) within 7 days of investigational product administration 10. --- G20210A ---

49 Retrospective Study of the Prevalence of Antiphospholipid Antibodies in the Population of Hemodialysis Patients at the CHU Brugmann Hospital

In patients with a chronic renal disease at the terminal stage, extrarenal epuration is essential for the control of clinico-biological complications. Two extrarenal epuration techniques are currently available: peritoneal dialysis (using the peritoneal membrane of the patient) and hemodialysis, requiring the use of an external biocompatible membrane known as 'dialysis filter'. This technique requires a vascular access (arteriovenous fistula or dialysis catheter). The thrombosis of vascular accesses represents a major cause of morbidity and mortality in hemodialysis patients. Thrombosis are more frequent when using synthetic prosthetic arteriovenous fistula instead of native arteriovenous fistula. Antiphospholipid Syndrome (APLS) is a rare autoimmune disease characterized by arterial thrombosis, venous thrombosis and obstetrical complications such as as defined by the Sidney's criteria. In the general population, the presence of antiphospholipid antibodies is associated with an increased risk of thromboembolic events. In the nephrological population, this prevalence is higher in hemodialysis patients compared to patients on peritoneal dialysis or non-dialyzed patients. Up to 37% of hemodialysis patients are positive for antiphospholipid antibodies and this biology is associated with thrombotic events and vascular access thromboses. However, some studies do not report this association and there is currently no consensus in terms of the therapeutic management of these patients. Some factors influencing the positivity for antiphospholipid antibodies have been reported: smoking, age, the presence of a non-glomerular nephropathy, hypoalbuminaemia, the use of a central venous catheter for dialysis or the use of a non-biocompatible dialysis membrane. Taking into account the conflicting data from the literature, it seems important to study the respective role(s) of 3 types of antiphospholipid antibodies in the occurrence of thrombo- embolic events in patients undergoing dialysis within the CHU Brugmann Hospital.

NCT03893357 Antiphospholipid Syndrome Other: Data extraction from medical files

MeSH:Antiphospholipid Syndrome

Inclusion Criteria: - All patients undergoing dialysis within the CHU Brugmann Hospital Exclusion Criteria: - Mutation of factor V - Mutation G20210A of the prothrombin gene - Protein C deficiency - Protein S deficiency - Antithrombin III deficiency Inclusion Criteria: - All patients undergoing dialysis within the CHU Brugmann Hospital Exclusion Criteria: - Mutation of factor V - Mutation G20210A of the prothrombin gene - Protein C deficiency - Protein S deficiency - Antithrombin III deficiency Antiphospholipid Syndrome Antiphospholipid Syndrome null --- G20210A ---

Inclusion Criteria: - All patients undergoing dialysis within the CHU Brugmann Hospital Exclusion Criteria: - Mutation of factor V - Mutation G20210A of the prothrombin gene - Protein C deficiency - Protein S deficiency - Antithrombin III deficiency Inclusion Criteria: - All patients undergoing dialysis within the CHU Brugmann Hospital Exclusion Criteria: - Mutation of factor V - Mutation G20210A of the prothrombin gene - Protein C deficiency - Protein S deficiency - Antithrombin III deficiency Antiphospholipid Syndrome Antiphospholipid Syndrome null --- G20210A --- --- G20210A ---

50 Markers of Microvascular Lesion in Adult Patients With Acquired Sudden Cochelo-vestibular Deficiency

The roles of thrombophilia and cardiovascular risk factors in sudden sensorineural hearing loss (SSNHL) remain controversial. Cochlear micro-thrombosis has been hypothesized as a possible pathogenic mechanism of SSNHL. The objective was thus to measure the levels of markers of macrovascular thrombosis and microvascular risk factors

NCT03919474 Idiopathic SSNHL Age Over 18 Diagnostic Test: microvascular markers

MeSH:Hearing Loss

HPO:Hearing impairment

Thrombophilia screening included measurements of antithrombin , protein C, protein S, factor V Leiden, prothrombin G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T, antiphospholipid antibodies anticardiolipin IgG and IgM and anti-beta2 glycoprotein 1 IgG), dilute Russell viper venom time , Rosner index, factor VIII, von Willebrand factor (vWF) activity and antigen. --- G20210A ---

51 A Randomized, Multicenter, Double-Blind, Placebo Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of IgPro10 (Intravenous Immunoglobulin, Privigen®) for the Treatment of Adults With Systemic Sclerosis

This randomized, multicenter, double-blind (DB), placebo controlled, phase 2 study will evaluate the efficacy and safety of IgPro10. The DB Treatment Period will be followed by a 24-week Open-label (OL) Treatment Period. Eligible subjects will be randomized at Baseline in a 2:1 ratio of treatment IgPro10 or placebo in the DB Treatment Period. All subjects who enter OL Treatment Period will receive IgPro10.

NCT04138485 Diffuse Cutaneous Systemic Sclerosis Biological: IgPro10 Biological: Placebo

MeSH:Scleroderma, Systemic Scleroderma, Diffuse Sclerosis

- History of documented thrombotic episode eg, PE, DVT, myocardial infarction, thromboembolic stroke at any time Note: past superficial thrombophlebitis more than two years from Screening is not exclusionary - Documented thrombophilic abnormalities including blood hyperviscosity, protein S or protein C deficiency, anti-thrombin-3 deficiency, plasminogen deficiency, antiphospholipid syndrome, Factor V Leiden mutation, dysfibrinogenemia, or prothrombin G20210A mutation - Greater than 3 specified current risk factors for TEEs (documented and currents conditions): atrial fibrillation, coronary disease, diabetes mellitus, dyslipidemia, hypertension, obesity (Body Mass Index ≥ 30 kg/m2), recent significant trauma, and immobility (wheelchair-bound or bedridden) - Ongoing active serious infection at Screening (including, but not limited to, pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess) - Malignancy in the past 2 years, except for non-melanoma skin cancer, cervical carcinoma in situ, or other in situ cancer if it has been excised and treated within in the past year - Known hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined by total urine protein concentration > 0.2 g/L) - Known IgA deficiency or serum IgA level < 5% lower limit of normal Inclusion Criteria: - 1. Age ≥18 years (male or female) at time of providing written informed consent - Documented diagnosis of SSc according to ACR / EULAR criteria 2013 - mRSS ≥ 15 and ≤ 45 - Disease duration ≤ 5 years defined as the time from the first non-Raynaud's phenomenon manifestation - Subjects within first 18 months of disease duration from first non-Raynaud's phenomenon manifestation. --- G20210A ---

- History of documented thrombotic episode eg, PE, DVT, myocardial infarction, thromboembolic stroke at any time Note: past superficial thrombophlebitis more than two years from Screening is not exclusionary - Documented thrombophilic abnormalities including blood hyperviscosity, protein S or protein C deficiency, anti-thrombin-3 deficiency, plasminogen deficiency, antiphospholipid syndrome, Factor V Leiden mutation, dysfibrinogenemia, or prothrombin G20210A mutation - Greater than 3 specified current risk factors for TEEs (documented and currents conditions): atrial fibrillation, coronary disease, diabetes mellitus, dyslipidemia, hypertension, obesity (Body Mass Index ≥ 30 kg/m2), recent significant trauma, and immobility (wheelchair-bound or bedridden) - Ongoing active serious infection at Screening (including, but not limited to, pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess) - Malignancy in the past 2 years, except for non-melanoma skin cancer, cervical carcinoma in situ, or other in situ cancer if it has been excised and treated within in the past year - Known hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined by total urine protein concentration > 0.2 g/L) - Known IgA deficiency or serum IgA level < 5% lower limit of normal Diffuse Cutaneous Systemic Sclerosis Scleroderma, Systemic Scleroderma, Diffuse Sclerosis null --- G20210A ---

HPO Nodes