|drug1062||Discontinuation of ACEi/ARB Wiki||1.00|
|D000077299||Healthcare-Associated Pneumonia NIH||1.00|
|D053717||Pneumonia, Ventilator-Associated NIH||0.33|
There is one clinical trial.
Recent data from some of the earliest and worst affected countries of COVID-19 suggest a major overrepresentation of hypertension and diabetes among COVID-19-related deaths and among patients experiencing severe courses of the disease. The vast majority of patients with hypertension and/or diabetes are taking drugs targeting the renin-angiotensin system (RAS) because of their blood pressure-lowering and/or kidney-protective effects. Importantly, the virus causing COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the transmembrane protein angiotensin converting enzyme 2 (ACE2) - an important component of RAS - for host cell entry and subsequent viral replication. ACE2 is normally considered to be an enzyme that limits airway inflammation via effects in RAS and increased ACE2 activity seems to alleviate acute respiratory distress syndrome (ARDS). Importantly, evidence from human studies as well as rodent studies suggests that the inhibition of RAS by angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) leads to upregulation of ACE2, and treatment with ARB leads to attenuation of SARS-CoV-induced ARDS. This is of interest, as the vast majority of deaths from COVID-19 are due to ARDS and expression of ACE2 has previously been shown to be reduced by the binding of SARS-CoV to ACE2. Thus, ACE inhibitors and ARBs have been suggested to alleviate the COVID-19 pulmonary manifestations. In contrast to these notions, concern has been raised that ACE2 upregulation (by RAS-inhibiting drugs) will multiply the cellular access points for viral entry and might increase the risk of severe progression of COVID-19. The multiplied viral entry points could perhaps explain the alarmingly high morbidity and mortality among COVID-19 patients with diabetes and/or hypertension. Thus, a delineation of the role of RAS for the course of COVID-19 is of crucial importance for the management of COVID-19 patients. Aim: This randomised clinical trial will investigate whether to continue or discontinue treatment with ACE inhibitors or ARBs in hospitalised patients with COVID-19.
Description: The primary endpoint is days alive and out of hospital within 14 days after recruitmentMeasure: Days alive and out of hospital within 14 days after recruitment Time: 14 days
Description: The key-secondary composite endpoint is the occurrence of worsening of COVID-19 as assessed by (whichever comes first): Severe respiratory insufficiency; defined by the occurrence of one of the following: PaO2/FiO2 ratio ≤40 kPa (300 mm Hg); PaO2, partial pressure of arterial oxygen; FiO2, percentage of inspired oxygen Commencement of non-invasive ventilation (NIV) Commencement of continuous CPAP (continuous positive airway pressure) treatment Commencement of high-flow oxygen therapy (HFOT); defined as an oxygen flow >16 l/min Referral to treatment in an intensive care unit DeathMeasure: Key-secondary composite endpoint: Occurrence of worsening of COVID-19 Time: 30 days
Description: Occurrence and time to occurrence of each of the components of the key-secondary composite endpointMeasure: Occurrence and time to occurrence of each of the components of the key-secondary composite endpoint Time: 30 days
Description: Kidney function assessed by plasma creatinineMeasure: Kidney function assessed by plasma creatinine Time: 30 days
Description: Duration of index hospitalisationMeasure: Duration of index hospitalisation Time: 30 days
Description: 30-day mortalityMeasure: 30-day mortality Time: 30 days
Description: Number of days alive during the intervention periodMeasure: Number of days alive during the intervention period Time: 30 days
Description: Number of participants not yet discharged at day 30Measure: Number of participants not yet discharged at day 30 Time: 30 days
Description: Number of readmissions after 30 days.Measure: Number of readmissions after 30 days. Time: 30 days
Description: Kidney function as assessed by eGFRMeasure: Kidney function as assessed by eGFR Time: 30 days
Description: To support the clinical findings, blood samples will be analysed for ACE, ACE2, aldosterone, angiotensin II and renin, and expression of ACE, interferon signatures and T cell exhaustion markers.Measure: Support for clinical findings via relevant blood markers Time: 30 days
Data processed on January 01, 2021.
An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.Drug Reports MeSH Reports HPO Reports