Blood Pressure Medications for COVID-19

Recruiting at 30 trial locations

Overseen By Ermina Moga

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ottawa Heart Institute Research Corporation

Must not be taking: ARB, ACEi

Disqualifiers: Severe aortic stenosis, Angioedema, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 30

Duration: 4 weeks

1155 Participants Needed

Trial Summary

What is the purpose of this trial?

The COVID-RASi study is an international randomized clinical trial that will evaluate the potential benefit of angiotensin modulators on clinical outcomes, in COVID-19 patients. The purpose of this study is to determine if renin-angiotensin system inhibitors (RASi), with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB), has a beneficial effect in patients with COVID-19 infections, by reducing ICU admission, ventilator requirement or death. We would also like to determine if there are differences between ACEi and ARB therapeutic treatments. With the increasing potential of long COVID symptoms, at the 1 year follow up, a primary endpoint will be the quality of life of study participants, as assessed by ongoing symptoms and/or the standardized questionnaires.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking ARB or ACEi medications.

What data supports the effectiveness of the drug Angiotensin-converting enzyme inhibitors (ACE inhibitors) and Angiotensin II Receptor Blockers for COVID-19?

Research shows that using ACE inhibitors and ARBs does not lead to worse outcomes in COVID-19 patients, meaning they are safe to continue using for those who need them for conditions like high blood pressure. ^{1 2 3 4 5}

Is it safe to use blood pressure medications like ACE inhibitors and ARBs for COVID-19?

Research suggests that ACE inhibitors and ARBs are generally safe for people with COVID-19, and patients are advised to continue using them unless a doctor recommends otherwise. ^{6 7 8 9 10}

How do ACE inhibitors and ARBs differ from other COVID-19 treatments?

ACE inhibitors and ARBs are unique because they target the renin-angiotensin-aldosterone system, which may help moderate the body's inflammatory response to COVID-19. Unlike other treatments, they work by increasing the expression of ACE2, a receptor that the virus uses to enter cells, which has led to debate about their effects on COVID-19 outcomes. ^{4 11 12 13 14}

Research Team

Peter Liu, MD

Principal Investigator

Ottawa Heart Institute Research Corporation

Eligibility Criteria

Adults diagnosed with COVID-19 can join this trial. Hospitalized patients must be 18 or older, while non-hospitalized ones need to be at least 40. They should have confirmed COVID-19 within the last month but not suffer from severe low blood pressure, high potassium levels, certain kidney issues, or conditions that make ACEi/ARB use unsafe.

Inclusion Criteria

I have been diagnosed with COVID-19 in the last 30 days.

I am 18 or older and currently admitted to the hospital.

I am 40 years old or older.

Exclusion Criteria

I have narrowing in the arteries of both my kidneys.

Your blood potassium level is higher than 5.5 mmol/L.

I am currently taking medication for blood pressure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants are randomized to receive ACEi, ARB, or no RASi treatment for COVID-19

4 weeks

Research-related follow-ups at 24 hours, 7 days, and 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on long-term outcomes

12 months

Phone call follow-ups at 6 months and 12 months

Treatment Details

Interventions

• Angiotensin converting enzyme inhibitor
• Angiotensin II Receptor Blockers

Trial Overview The study is testing if drugs called RAS inhibitors—specifically ACE inhibitors (ACEi) and Angiotensin II Receptor Blockers (ARB)—can improve outcomes for COVID-19 patients by reducing ICU stays, ventilator needs or death. It also compares the effectiveness of ACEi versus ARB on long-term quality of life.

Participant Groups

Group I: ARB treatment Experimental Treatment 1 Intervention

The physician will initiate any ARB and dose at their discretion.

Group II: ACEi treatment Experimental Treatment 1 Intervention

The physician will initiate any ACE inhibitor and dose at their discretion.

Group III: No Treatment (Standard of Care) Active Control 1 Intervention

Participants will be treated as per standardized care pathway according to province/state and institutional guidelines. Physicians will be reminded not to start ACEi or ARB throughout admission or to outpatients until active study participation is complete at 28 days post symptoms.

Angiotensin converting enzyme inhibitor is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as ACE inhibitors for:

• Hypertension
• Heart failure
• Diabetic nephropathy

Approved in United States as ACE inhibitors for:

• Hypertension
• Heart failure
• Diabetic nephropathy
• Left ventricular dysfunction

Approved in Canada as ACE inhibitors for:

• Hypertension
• Heart failure
• Diabetic nephropathy

Approved in Japan as ACE inhibitors for:

• Hypertension
• Heart failure

Approved in China as ACE inhibitors for:

• Hypertension
• Heart failure

Approved in Switzerland as ACE inhibitors for:

• Hypertension
• Heart failure
• Diabetic nephropathy

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Renin-angiotensin-system inhibitors and all-cause mortality in patients with COVID-19: a systematic review and meta-analysis of observational studies. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

Neither ACEIs nor ARBs are associated with respiratory distress or mortality in COVID-19 results of a prospective study on a hospital-based cohort. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Severity of COVID-19 infection in ACEI/ARB users in specialty hospitals: A retrospective cohort study. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Association of renin-angiotensin-aldosterone system inhibition with Covid-19 hospitalization and all-cause mortality in the UK biobank. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Meta-analysis of the association between angiotensin pathway inhibitors and COVID-19 severity and mortality. [2023]

7. Brazil pubmed.ncbi.nlm.nih.gov

Association between RAAS Antagonism and COVID-19-related Mortality in Patients with Overweight/Obesity-related Hypertension: A Retrospective Cohort Study. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

A consensus statement on the use of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in relation to COVID-19 (corona virus disease 2019). [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Impact of Treatment with Renin-Angiotensin System Inhibitors on Clinical Outcomes in Hypertensive Patients Hospitalized with COVID-19. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Cardiovascular Disease and Use of Renin-Angiotensin System Inhibitors in COVID-19. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Angiotensin-Converting Enzyme (ACE) Inhibitors May Moderate COVID-19 Hyperinflammatory Response: An Observational Study with Deep Immunophenotyping. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Continued In-Hospital Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use in Hypertensive COVID-19 Patients Is Associated With Positive Clinical Outcome. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. [2021]

14. Spain pubmed.ncbi.nlm.nih.gov

[Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors]. [2021]