Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019 (REPLACECOVID)
|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. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04338009|
Recruitment Status : Enrolling by invitation
First Posted : April 8, 2020
Last Update Posted : April 24, 2020
|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)|
|Estimated 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|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 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 score that ranks 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.
- All-Cause Death [ Time Frame: Up to 28 days ]
- Length of Hospital Stay [ Time Frame: Up to 28 days ]
- 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.
- Intensive care unit admission or respiratory Failure Requiring Mechanical Ventilation. [ Time Frame: Up to 28 days ]Composite
- 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).
- Number of 28-Day Ventilator-Free Days. [ Time Frame: Up to 28 days ]Number of days in 28-day period feee of invasive or non-invasive mechanical ventilation.
- Maximal change in NT-proBNP from baseline [ Time Frame: 28 days from enrollment ]Difference between NT-proBNP at the time of randomization and the maximum value
- Change in serum creatinine between randomization and discharge (or time of death) [ Time Frame: Up to 28 days ]as above
- Acute kidney injury during hospitalization [ Time Frame: Up to 28 days ]defined as Kidney Disease Improving Global Outcomes Stage 2 or higher or initiation of renal replacement therapy
- Proteinuria or Hematuria [ Time Frame: Up to 28 days ]Proteinuria or Hematuria detected on urinalysis
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|