Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019 (REPLACECOVID)
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|ClinicalTrials.gov Identifier: NCT04338009|
Recruitment Status : Completed
First Posted : April 8, 2020
Results First Posted : April 9, 2021
Last Update Posted : April 9, 2021
|Condition or disease||Intervention/treatment||Phase|
|COVID-19||Other: Discontinuation of ARB/ACEI Other: Continuation of ARB/ACEI||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||152 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||The Randomized Elimination or Prolongation of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Coronavirus Disease 2019|
|Actual Study Start Date :||March 31, 2020|
|Actual Primary Completion Date :||August 20, 2020|
|Actual Study Completion Date :||August 20, 2020|
Experimental: Discontinuation arm
The randomized intervention will be the discontinuation of ACEI/ARBs
Other: Discontinuation of ARB/ACEI
The randomized intervention will be the discontinuation of ACEI/ARBs. In all participants randomized to discontinuation, treating clinicians will be reminded about the medication discontinuation upon discharge and will be prompted to consider re-initiation of the medication at that time if appropriate, per the clinician's discretion.
Experimental: Continuation arm
The randomized intervention will be the continuation of ACEI/ARBs
Other: Continuation of ARB/ACEI
The randomized intervention will be the continuation of ACEI/ARBs at the doses previously prescribed for patients during their routine care. Clinicians will be encouraged to continue the randomized treatment but will be allowed to change the dose of ACEI/ARB or discontinue these medications if any compelling clinical reasons are identified (such as hypotension, hyperkalemia, acute kidney injury).
- Hierarchical Composite Endpoint [ Time Frame: Up to 28 days ]
The primary endpoint of the trial will be a global rank based on patient outcomes according to four factors: (1) time to death, (2) the number of days supported by invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), (3) the number of days supported by renal replacement therapy or pressor/inotropic therapy, and (4) a modified sequential Organ Failure Assessment (SOFA) score. The modified SOFA score will include the cardiac, respiratory, renal and coagulation domains of the SOFA score.
How to interpret the rank?: patients are ranked from worst to best outcomes, such that patients with bad outcomes are ranked at the top and patients who have the best outcomes are ranked at the bottom.
- All-Cause Death [ Time Frame: Up to 28 days ]
- Length of Hospital Stay [ Time Frame: Up to 28 days ]This outcome measurement looked at the median length of hospitalization.
- Length of ICU Stay, Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation [ Time Frame: Up to 28 days ]
- AUC SOFA [ Time Frame: Up to 28 days ]
The Area Under the Curve of the modified SOFA (AUC SOFA) from daily measurements, weighted to account for the shorter observation period among patients who die in-hospital.
How to interpret the AUC SOFA?: a higher area indicates more severe disease and/or longer hospitalization.The range is 0.1 to 377.3.
- Intensive Care Unit Admission or Respiratory Failure Requiring Mechanical Ventilation. [ Time Frame: Up to 28 days ]Need to be transferred to an intensive care unit or to supported by a breathing machine
- Hypotension Requiring Vasopressors, Inotropes or Mechanical Hemodynamic Support [ Time Frame: Up to 28 days ]Hypotension Requiring Vasopressors, inotropes or mechanical hemodynamic support (ventricular assist device or intra-aortic balloon pump).
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): NCT04338009
|United States, Pennsylvania|
|University of Pennsylvania Health System|
|Philadelphia, Pennsylvania, United States, 19104|