The McGill RAAS-COVID-19 Trial

McGill University Health Centre/Research Institute of the McGill University Health Centre46 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

COVID-19 Cardiovascular Diseases

Interventions

Temporarily holding the RAAS inhibitor [intervention]OTHER

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.

RAAS inhibitor [continued standard of care]OTHER

No intervention, Continuation RAAS inhibitor \[continued standard of care\].

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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.

Locations (1)

Muhc-Rimuhc

Montreal, Quebec, Canada

Outcomes

Primary Outcomes

Global rank score

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.

Time frame: Baseline - day 7

Data from ClinicalTrials.gov

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