Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The McGill RAAS-COVID-19 Trial (RAAS-COVID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04508985
Recruitment Status : Not yet recruiting
First Posted : August 11, 2020
Last Update Posted : August 19, 2020
Sponsor:
Collaborators:
Jewish General Hospital (Montreal, Quebec, Canada)
Montreal General Hospital (Montreal, Quebec, Canada)
Université de Lorraine, Centre d'Investigation Clinique- Plurithématique Inserm
Information provided by (Responsible Party):
Abhinav Sharma, 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.

Condition or disease Intervention/treatment Phase
COVID-19 Cardiovascular Diseases Other: Temporarily holding the RAAS inhibitor [intervention] Other: RAAS inhibitor [continued standard of care] Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Open-label, 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 on discharge) versus a strategy continuation of RAAS inhibition.
Masking: None (Open Label)
Masking Description: The patient and the treating doctor will be informed of the assigned treatment.
Primary Purpose: Treatment
Official Title: Management of Renin-Angiotensin-Aldosterone System Blockade in Patients Admitted in Hospital With Confirmed Coronavirus Disease (COVID-19) Infection: The McGill RAAS-COVID-19 Randomized Controlled Trial
Estimated Study Start Date : September 1, 2020
Estimated Primary Completion Date : January 1, 2021
Estimated Study Completion Date : September 1, 2021

Arm Intervention/treatment
Experimental: 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.
Other: 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
No intervention, Continuation RAAS inhibitor [continued standard of care].
Other: RAAS inhibitor [continued standard of care]
No intervention, Continuation RAAS inhibitor [continued standard of care].




Primary Outcome Measures :
  1. Global rank score [ Time Frame: 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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04508985


Contacts
Layout table for location contacts
Contact: Abhinav Sharma, MD 5149341934 abhinav.sharma@mcgill.ca
Contact: Julie Lebel, PM 5147912705 julie.lebel@muhc.mcgill.ca

Sponsors and Collaborators
McGill University Health Centre/Research Institute of the McGill University Health Centre
Jewish General Hospital (Montreal, Quebec, Canada)
Montreal General Hospital (Montreal, Quebec, Canada)
Université de Lorraine, Centre d'Investigation Clinique- Plurithématique Inserm
Investigators
Layout table for investigator information
Principal Investigator: Abhinav Sharma, MD McGill University Health Centre/Research Institute of the McGill University Health Centre
Additional Information:
Publications:
Nerenberg KA, Zarnke KB, Leung AA, Dasgupta K, Butalia S, McBrien K, Harris KC, Nakhla M, Cloutier L, Gelfer M, Lamarre-Cliche M, Milot A, Bolli P, Tremblay G, McLean D, Padwal RS, Tran KC, Grover S, Rabkin SW, Moe GW, Howlett JG, Lindsay P, Hill MD, Sharma M, Field T, Wein TH, Shoamanesh A, Dresser GK, Hamet P, Herman RJ, Burgess E, Gryn SE, Grégoire JC, Lewanczuk R, Poirier L, Campbell TS, Feldman RD, Lavoie KL, Tsuyuki RT, Honos G, Prebtani APH, Kline G, Schiffrin EL, Don-Wauchope A, Tobe SW, Gilbert RE, Leiter LA, Jones C, Woo V, Hegele RA, Selby P, Pipe A, McFarlane PA, Oh P, Gupta M, Bacon SL, Kaczorowski J, Trudeau L, Campbell NRC, Hiremath S, Roerecke M, Arcand J, Ruzicka M, Prasad GVR, Vallée M, Edwards C, Sivapalan P, Penner SB, Fournier A, Benoit G, Feber J, Dionne J, Magee LA, Logan AG, Côté AM, Rey E, Firoz T, Kuyper LM, Gabor JY, Townsend RR, Rabi DM, Daskalopoulou SS; Hypertension Canada. Hypertension Canada's 2018 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults and Children. Can J Cardiol. 2018 May;34(5):506-525. doi: 10.1016/j.cjca.2018.02.022. Epub 2018 Mar 1.

Layout table for additonal information
Responsible Party: Abhinav Sharma, Cardiologist, McGill University Health Centre/Research Institute of the McGill University Health Centre
ClinicalTrials.gov Identifier: NCT04508985    
Other Study ID Numbers: MP-37-2021-6614
First Posted: August 11, 2020    Key Record Dates
Last Update Posted: August 19, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be de-identified and shared among all collaborators.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Immediate access to the data

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Abhinav Sharma, McGill University Health Centre/Research Institute of the McGill University Health Centre:
Renin
Angiotensin
Aldosterone
coronavirus
Cardiovascular Diseases
COVID-19
Additional relevant MeSH terms:
Layout table for MeSH terms
Cardiovascular Diseases