Adult patients with a diagnosis of COVID-19 requiring hospitalization in a non-ICU and on prior therapy with RAS blockers
Conditions
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects meeting all of the following criteria will be considered for enrolment into the study: 1. Age = 18 year/old 2. Chronically treated with RAS blockers (ACE inhibitors or ARBs on the last prescription prior to admission with a treatment duration = 1 month)) 3. Diagnosis of COVID-19 confirmed by the presence of SARS-CoV-2 on any biological sample with any detection method 4. Patients hospitalized in a non-ICU 5. Pregnancy test at inclusion visit for women of childbearing potential 6. Women of childbearing potential must agree to use adequate contraception according to Recommendations related to contraception and pregnancy testing in clinical trials, by Clinical Trial Facilitation Group (CTFG) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 277 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 277
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the study: 1. Shock requiring vasoactive agents 2. Acute respiratory distress syndrome requiring invasive mechanical ventilation 3. Circulatory assistance 4. History of malignant hypertension according to the definition of the 2018 ESC/ESH guidelines on hypertension 5. Uncontrolled blood pressure despite the use of five antihypertensive drugs 6. History of nephrotic syndrome 7. History of hospitalization for hemorrhagic stroke in the past 3 months 8. RAS blockers therapy previously stopped > 48h 9. No affiliation to the French Health Care System “Sécurité Sociale” 10. Inability to obtain informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effect of discontinuation versus continuation of RAS blockers on the clinical course of patients with confirmed COVID-19 infection leading to hospitalization;Secondary Objective: 1. Evaluate the cardiovascular safety of RAS blockers discontinuation in patients hospitalized for COVID-19 by a composite endpoint of MACE. 2. Evaluate the efficacy of RAS blockers discontinuation in patients hospitalized for COVID-19 by the secondary efficacy endpoints. ;Primary end point(s): Primary endpoint: Time to clinical improvement from day 0 to day 28. Clinical improvement is defined as an improvement of two points on a seven-category ordinal scale, or live discharge from the hospital, whichever comes first, as recommended by the WHO R&D Blueprint expert group (3). The seven-category ordinal scale consisted of the following categories: 1. not hospitalized with resumption of normal activities 2. not hospitalized, but unable to resume normal activities 3. hospitalized, not requiring supplemental oxygen 4. hospitalized, requiring supplemental oxygen 5. hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both 6. hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. death. ;Timepoint(s) of evaluation of this end point: 28 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Primary safety endpoint: major adverse cardiac events defined as the composite of cardiovascular death, myocardial infarction, stroke or acute heart failure at day 28. 2. Key secondary efficacy endpoints: - Clinical status as assessed with the seven-category ordinal scale on days 7, 14 and 28. - Number of days alive free of oxygen. - Number of days alive outside hospital during 28 days after randomization. - Number of days alive free of intensive-care unit (ICU) admission or mechanical ventilation (invasive or non-invasive) 28 days after randomization. - Number of days alive free of mechanical ventilation (invasive or non-invasive) 28 days after randomization. - Number of days alive free of ICU admission 28 days after randomization. - Rate of all-cause mortality at day 28. - Rate of cardiovascular death at day 28. - Number of days alive free of acute kidney injury during hospitalization. ;Timepoint(s) of evaluation of this end point: 28 days | — |
Countries
France
Contacts
Public ContactCarla VANDENABELE
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed