SNPMiner Trials (Home Page)
Report for Mutation L98H
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 4 clinical trials
Clinical Trials
1 Surveillance of Azole Resistance in Aspergillus
Primary objectives: 1. To investigate the prevalence of azole resistance in Aspergillus clinical isolates collected in participating hospitals in Taiwan 2. To investigate the prevalence of azole resistance in Aspergillus environmental isolates in Taiwan 3. To characterize the molecular mechanisms of azole resistance in Aspergillus isolates in Taiwan 4. To investigate the clonality of Aspergillus clinical and environmental isolates in Taiwan 5. To describe the genetic relationships between local resistant strains with global strains Secondary objective: 1. To describe the clinical characteristics and treatment outcome of patients with proven or probable invasive aspergillosis 2. To evaluate the clinical impact of azole resistance in patients with proven or probable invasive aspergillosis in a case-control study
NCT03024281 Infection; Aspergillus MeSH:Aspergillosis
Multiple amino acid substitutions in the cyp51A gene have been described to be associated with azole resistance that emerges during azole treatment, while a resistance mechanism, TR34/L98H mutation in cyp51A, has been linked to the agricultural use of azole fungicides in Europe, which have also been widely used in Taiwan for years. --- L98H ---
Primary Outcomes
Description: The proportion of patients with complete response or partial response according to the definition described in "Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. Sep 1 2008;47(5):674-683."
Measure: Treatment success Time: 6 weeks after diagnosis of proven or probable invasive aspergillosisSecondary Outcomes
Description: The proportion of non-survivors. Discharge against medical advice and in critical condition and lost to follow up will categorized as mortality.
Measure: All-cause mortality Time: 6 weeks after diagnosis of proven or probable invasive aspergillosisDescription: The proportion of non-survivors. Discharge against medical advice and in critical condition and lost to follow up will categorized as mortality.
Measure: All-cause mortality Time: 12 weeks after diagnosis of proven or probable invasive aspergillosisDescription: The proportion of patients with breakthrough mold infections
Measure: Breakthrough mold infections Time: 6 weeks after diagnosis of proven or probable invasive aspergillosisDescription: The proportion of patients with breakthrough invasive fungal diseases defined as occurrence of a proven or probable invasive fungal diseases according to EORTC/MSG revised definitions while on systemic antifungal therapy or within 15 days of discontinuation of antifungal use
Measure: Breakthrough invasive fungal diseases Time: 12 weeks after diagnosis of proven or probable invasive aspergillosisDescription: The proportion of patients with complete response or partial response.
Measure: Treatment success Time: 12 weeks after diagnosis of proven or probable invasive aspergillosis2 PCR Based Detection of Azole Resistance in A. Fumigatus to Improve Patient Outcome. A Prospective Multicenter Observational Study.
A standard treatment protocol for invasive aspergillosis (IA) will be implemented in several academic hematology centers in the Netherlands in which a diagnostic test demonstrating azole resistance by multiplex real-time polymerase chain reaction will guide the choice of appropriate antifungal treatment. Objectives: 1. Improve the outcome of patients infected with azole resistant A. fumigatus by the early detection of Resistance Associated Mutations (RAMs) and with this the earlier initiation of the most appropriate therapy. 2. Monitor the prevalence of invasive aspergillosis due to strains carrying the TR34/L98H or the TR46/T289A/Y121F resistance associated mutations in the Netherlands.
NCT03121235 Aspergillosis, Invasive Pulmonary Diagnostic Test: PCR based detection of azole resistance in A. fumigatus MeSH:Aspergillosis Invasive Pulmonary Aspergillosis
2. Monitor the prevalence of invasive aspergillosis due to strains carrying the TR34/L98H or the TR46/T289A/Y121F resistance associated mutations in the Netherlands. --- L98H ---
Primary Outcomes
Description: Incidence of antifungal treatment failure in patients with the presence of RAM detected by the AsperGenius® resistance PCR. This incidence will be compared with a fixed failure rate set at 75%, based on the observed treatment failure in patients treated with voriconazole that were shown to carry azole resistant A. fumigatus.
Measure: Incidence of antifungal treatment failure Time: 12 weeksSecondary Outcomes
Description: This will be compared with a fixed mortality of 50%.
Measure: Demonstrate that early detection of azole resistance reduces the overall mortality. Time: 6 weeksDescription: Posaconazole step down therapy will be considered effective if <35% of the patients treated with posaconazole oral monotherapy show progression of their invasive aspergillosis after documented response after at least 14 days of IV antifungal therapy.
Measure: Demonstrate that a step down to oral posaconazole is a reasonable treatment option in patients that have responded to at least 2 weeks of IV antifungal therapy. Time: 12 weeksDescription: A group that received appropriate antifungal therapy soon will be compared with a group that received treatment late.
Measure: Comparison of antifungal treatment failure in patients with the presence of RAM. Time: 24 weeks3 Prospective Multicenter Evaluation of the MycoGenie Kit for the Diagnosis of Invasive Aspergillosis in Hematological Patients
The purpose of this study is to evaluate the performances of the real-time PCR ADEMTECH kit of DNA extraction and detection of Aspergillus fumigatus in serum samples in patients at high-risk for invasive aspergillosis (IA). DNA detection will be associated with detection of TR34/L98H mutations in cyp51A gene, which confer azole resistance.
NCT03349931 Invasive Aspergillosis in Patients With Onco-haematological Diseases Diagnostic Test: DNA extraction and detection of Aspergillus fumigatus in serum samples MeSH:Aspergillosis
DNA detection will be associated with detection of TR34/L98H mutations in cyp51A gene, which confer azole resistance. --- L98H ---
Detection of TR34 and L98H mutations in the A. fumigatus single-copy number gene cyp51A.. Inclusion Criteria: 1. Adult Patients (≥ 18 years) hospitalized in onco hematologic unit or in hematopoietic stem cell transplantation (HSCT) unit 2. Patients with acute leukemia undergoing induction for AML, ALL, chimotherapy with neutopenia >10 days or Patients undergoing allogeneic stem cell chemotherapy transplantation 3. Patients with biweekly screening for GM detection in serum Exclusion Criteria: 1. Patient < 18 years-old (minor) 2. Informed consent not available 3. Patient without affiliation to French social insurance 4. Patient without biweekly screening for GM detection in serum Inclusion Criteria: 1. Adult Patients (≥ 18 years) hospitalized in onco hematologic unit or in hematopoietic stem cell transplantation (HSCT) unit 2. Patients with acute leukemia undergoing induction for AML, ALL, chimotherapy with neutopenia >10 days or Patients undergoing allogeneic stem cell chemotherapy transplantation 3. Patients with biweekly screening for GM detection in serum Exclusion Criteria: 1. Patient < 18 years-old (minor) 2. Informed consent not available 3. Patient without affiliation to French social insurance 4. Patient without biweekly screening for GM detection in serum Invasive Aspergillosis in Patients With Onco-haematological Diseases Aspergillosis Accurate diagnosis of invasive pulmonary aspergillosis (IPA) in patients at high risk of invasive fungal infection remains challenging due to difficulties in differentiating IPA from pulmonary infections caused by other molds or bacteria on clinical and radiological grounds. --- L98H ---
Azole resistance in A. fumigatus is associated mainly with mutations in the cyp51A gene, and among several mutations described, the most frequent is the mutation comprising a 34-bp tandem repeat (TR34) and the L98H alteration. --- L98H ---
This multiplex assay detects DNA from the A. fumigatus species complex by targeting the multicopy 28S rRNA gene and specific TR34 and L98H mutations in the single-copy number cyp51A gene of A. fumigatus. --- L98H ---
Primary Outcomes
Description: Determination of the performances (Sensitivity, specificity, PPV and NPV) of the kit
Measure: Performance of PCR for Aspergillosis diagnosis Time: 6 monthsSecondary Outcomes
Description: Detection of TR34 and L98H mutations in the A. fumigatus single-copy number gene cyp51A.
Measure: Detection of azole resistance Time: 6 months4 Prospective Multi-center Surveillance Study on the Prevalence of Azole-resistant Aspergillus Spp. in Clinical Isolates ot Patients With Pulmonary Colonization or Invasive Infections in Switzerland
Prospective multi-center surveillance study on the prevalence of azole-resistant Aspergillus spp. in clinical isolates of patients with pulmonary colonization or invasive infections in Switzerland
NCT03443336 Pulmonary Aspergillosis MeSH:Aspergillosis Pulmonary Aspergillosis
These mutations, including TR34/L98H and TR46/Y121F/T289A have been identified in the environment and have been demonstrated to cause resistance to azole fungicides used in agriculture. --- L98H ---
Primary Outcomes
Description: Distribution of antifungal susceptibility profile of all tracheal and urinary samples in clinical Aspergillus isolates
Measure: Azole-resistance in Aspergillus (A.) fumigatus Time: start of study until end of study (July 2017 until December 2018)