The McGill RAAS-COVID-19 Trial
- Conditions
- COVID-19Cardiovascular Diseases
- Interventions
- Other: Temporarily holding the RAAS inhibitor [intervention]Other: RAAS inhibitor [continued standard of care]
- Registration Number
- NCT04508985
- Lead Sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Brief Summary
Coronavirus disease (COVID-19) related pneumonia significantly impact patients with underlying cardiovascular (CV) conditions. Animal studies suggest that drugs commonly used to treated CV diseases may increase the ability of COVID-19 to infect cells. The RAAS-COVID-19 trial aims to assess whether temporarily holding these CV drugs in patients who are admitted with COVID-19, versus continuing them, in patients admitted with COVID-19 can impact short term outcomes.
- Detailed Description
Open-label, pragmatic, randomized, study of approximately 40 adults. The following groups of participants will be considered: i) within 48 hours of diagnosis of COVID-19; ii) who have received a diagnosis of COVID-19 from another facility and are within 48 hours of transfer to a study recruitment site (Royal Victoria Hospital, Montreal General Hospital, and Jewish General Hospital \[all in Montreal, Quebec, Canada\]). Participants will be randomized 1:1 to an upfront temporary discontinuation) of RAAS inhibition for the duration of the hospitalization (and to consider re-initiate after day 7 of admission or on discharge) versus a strategy continuation of RAAS inhibition. Re-initiation of held RAAS inhibition will be based on treating team's clinical judgement. The RAAS-COVID-19 RCT will evaluate whether an upfront strategy of temporary discontinuation of RAAS inhibition compared to the continuation of RAAS inhibition among patients admitted with established COVID-19 infection and on chronic RAAS inhibition therapy impacts short term clinical outcomes and biomarkers.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 46
- Age ≥ 18 years old.
- Hospitalization with a Covid-19 infection
- Chronically treated with RAAS blockers (ACE inhibitors or ARBs on the last prescription prior to admission with a treatment duration ≥ 1 month
- Diagnosis of COVID-19 confirmed by the presence of SARS-CoV-2 on any biological sample
- Participants are within 48 hours of diagnosis of COVID-19 or have received a diagnosis of COVID-19 from another facility and are within 48 hours of transfer to a study recruitment site
- Shock requiring vasoactive agents.
- Requiring invasive mechanical ventilation.
- History of malignant hypertension
- Use of five or more antihypertensive drugs.
- History of heart failure with reduced ejection fraction
- History of hospitalization for acute heart failure in past 3 months
- History of hospitalization for hemorrhagic stroke in the past 3 months.
- History of CKD with an eGFR <45 ml/min/1.73m2
- History of COPD GOLD III/IV
- History of end-stage dementia
- History of active liver cirrhosis
- RAAS blockers therapy previously stopped > 48h.
- Anticipated discharge in less than 24 hours.
- History of current active cancer receiving chemotherapy
- Inability to obtain informed consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Intervention Temporarily holding the RAAS inhibitor [intervention] Temporarily holding the RAAS inhibitor. Among participants who will be randomized to the intervention arm, a possible guideline-directed alternative to anti-hypertensive medication alternatives will be provided to the treating physician team. Continuation of standard of care RAAS inhibitor [continued standard of care] No intervention, Continuation RAAS inhibitor \[continued standard of care\].
- Primary Outcome Measures
Name Time Method Global rank score Baseline - day 7 The primary end point is a global rank score which is applied to all participants. The global rank sum is based on the following endpoints (and corresponding score): Death (7); Transfer to ICU for Invasive ventilation (6); Transfer to ICU for other indication (5); Non-fatal MACE (Any of the following - MI, Stroke, Acute HF, new onset Afib) (4); Length of stay \> 4 days (3); Development of acute kidney injury (\>40% decline in eGFR or doubling of serum Cr) (2); Urgent intravenous treatment for high blood pressure/hypertensive crisis (2); \>30% Increase in baseline high sensitivity troponin (1); \>30% increase in baseline BNP (1); Increase in baseline CRP to 48 hours \>30%(1); Lymphocyte count drop \>30% (1).
The primary endpoint will be assessed from baseline to day 7 (or day of discharge if occurs before day 7). Participants will receive a weighted score depending on the events experienced. The global rank sum score will then be averaged and compared between treatment arms.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Muhc-Rimuhc
🇨🇦Montreal, Quebec, Canada