Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors and Adverse Outcomes in Patients With COVID19

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

Detailed Description
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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.

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

Conditions
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Corona Virus Infection, COVID-19

Intervention / Treatment
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* Other: Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1<br>Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors | Other: Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors<br>* Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors<br>|
| Other: Group 2<br>Suspension of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors | Other: Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors<br>* Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blockers of angiotensin receptor, Angiotensin-converting enzyme inhibitors, SARS-CoV2