Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors and Adverse Outcomes in Patients With COVID19 (BRACE-CORONA)

Suspension of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors and Adverse Outcomes in Hospitalized Patients With Coronavirus Infection (COVID-19). A Randomized Trial

Suspension of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors and Adverse Outcomes in Hospitalized Patients With Coronavirus Infection.

Study Overview

• Status: Unknown
• Conditions: COVID-19; Corona Virus Infection
• Intervention / Treatment: Other: Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors

Detailed Description

Several interactions by pre-existing therapies for chronic diseases, therapies used by SARS-CoV2 infection generate doubts about risks and benefits. Among these situations in which the current data indicate a situation of equipoise would be about the maintenance or suspension of ACEI / BRA in patients with SARS-CoV2 infection. Increasing the expression of ECA-2 could increase the binding to the virus, however, there are studies that indicate this increase in ECA-2 could be protective. So far, there is no clinical evidence to confirm any of the theories, and this question can only be clarified through a randomized clinical trial.

The objective is to evaluate the impact of the suspension of the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (BRA) on the length of hospital stay and on the mortality of patients with SARS-CoV2 infection.

• Study Type: Interventional
• Enrollment (Anticipated): 700
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • Recruiting
    • Idor
    • Contact: Renato D. Lopes, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients hospitalized with COVID-19 diagnosis using ACE inhibitors or blockers of angiotensin receptor;
• Patients ≥ 18 years old;
• Maximum use of 3 antihypertensive drugs;
• Sign the consent form.

Exclusion Criteria:

• Severe evolution with orotracheal intubation, use of mechanical ventilation and / or hemodynamic instability in the first 24 hours until COVID-19 diagnosis confirmation;
• Patients hospitalized per decompensated congestive heart failure in the last 12 months;
• Use of Sacubitril/Valsartan
• Pregnancy
• Recent acute renal failure and shock

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group 1; Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors	Other: Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors; Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors
Other: Group 2; Suspension of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors	Other: Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors; Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median days alive and out of the hospital	The primary outcome of the study will be days alive and outside the hospital (DAOH) at 30 days. This endpoint will be calculated for each included patient and the calculation will be from the date of randomization to the 30-day post-randomization. The DAOH endpoint represents the follow-up time (30 days) subtracted from the hospitalization days and/or the days between death and the end of follow-up.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse cardiovascular outcomes and new worsening heart failure	Cardiovascular outcomes such as progression of COVID-19, mortality (general and cardiovascular), acute myocardial infarction, stroke / TIA, new heart failure or worsening of pre-existing HF, myocarditis, pericarditis, arrhythmias requiring treatment, phenomena thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure. All events will be reported according to CTCAE 4.0	30 days
Cardiovascular biomarkers related to COVID-19	Evaluate levels of biomarkers [troponin, type B natriuretic peptide (BNP), N-terminal natriuretic peptide type B (NT-ProBNP), D-dimer, total lymphocytes , CD4, CD8, macrophages, cytokines, in addition to biomarkers detected by proteomics and metabolomics].	up to 30 days

Collaborators and Investigators

• Sponsor: D'Or Institute for Research and Education
• Collaborators: Brazilian Clinical Research Institute
• Investigators: Principal Investigator: Renato D. Lopes, MD, PhD, D'Or Institute for Research and Education

Publications and helpful links

General Publications

• Macedo AVS, de Barros E Silva PGM, de Paula TC, Moll-Bernardes RJ, Mendonca Dos Santos T, Mazza L, Feldman A, Arruda GDAS, de Albuquerque DC, de Sousa AS, de Souza OF, Gibson CM, Granger CB, Alexander JH, Lopes RD. Discontinuing vs continuing ACEIs and ARBs in hospitalized patients with COVID-19 according to disease severity: Insights from the BRACE CORONA trial. Am Heart J. 2022 Jul;249:86-97. doi: 10.1016/j.ahj.2022.04.001. Epub 2022 Apr 8.
• Lopes RD, Macedo AVS, de Barros E Silva PGM, Moll-Bernardes RJ, Dos Santos TM, Mazza L, Feldman A, D'Andrea Saba Arruda G, de Albuquerque DC, Camiletti AS, de Sousa AS, de Paula TC, Giusti KGD, Domiciano RAM, Noya-Rabelo MM, Hamilton AM, Loures VA, Dionisio RM, Furquim TAB, De Luca FA, Dos Santos Sousa IB, Bandeira BS, Zukowski CN, de Oliveira RGG, Ribeiro NB, de Moraes JL, Petriz JLF, Pimentel AM, Miranda JS, de Jesus Abufaiad BE, Gibson CM, Granger CB, Alexander JH, de Souza OF; BRACE CORONA Investigators. Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial. JAMA. 2021 Jan 19;325(3):254-264. doi: 10.1001/jama.2020.25864.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2020
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: April 25, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Actual): July 2, 2020
• Last Update Submitted That Met QC Criteria: July 1, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV2; Blockers of angiotensin receptor; Angiotensin-converting enzyme inhibitors
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Infections; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists
• Other Study ID Numbers: PRJ_2003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No