Blood Pressure Medications for COVID-19

Not currently recruiting at 37 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether certain blood pressure medications, ACE inhibitors (Angiotensin-converting enzyme inhibitors) and ARBs (Angiotensin II Receptor Blockers), can aid people with COVID-19. Researchers aim to determine if these drugs reduce the risk of severe outcomes, such as needing a ventilator or ICU admission. The study also compares the effectiveness of ACE inhibitors to ARBs. It is open to individuals diagnosed with COVID-19 in the past month who are not already using these medications and have no conditions that prevent their use. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ACE inhibitors and ARBs are generally safe. Studies have found that these medications do not increase the risk of severe COVID-19 or mortality. For instance, one study found that using these drugs did not affect COVID-19 outcomes, such as the need for additional medical support. Another analysis showed no significant change in death rates for people taking these medications. Additionally, lab tests demonstrated that these drugs do not harm cells during a COVID-19 infection. Overall, ACE inhibitors and ARBs are well-tolerated, with no evidence suggesting they worsen COVID-19. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs) for COVID-19 treatment because these medications could potentially modulate the body's response to the virus uniquely. Unlike traditional COVID-19 treatments that mainly focus on antiviral action, ACE inhibitors and ARBs work by affecting the renin-angiotensin system, which plays a role in blood pressure regulation and inflammatory responses. This could potentially help in reducing severe inflammatory responses and improving outcomes for patients with COVID-19. By targeting this different pathway, these medications might offer an innovative approach to managing the disease, especially in patients who also suffer from high blood pressure.

What evidence suggests that this trial's treatments could be effective for COVID-19?

Research suggests that certain medications, called ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), might help treat COVID-19 symptoms. In this trial, participants will join different treatment arms to explore these possibilities. One arm will receive ACEi treatment, while another will receive ARB treatment. Studies have shown that these medications can benefit COVID-19 patients and those recovering from the virus. Some observations indicate that they might lead to better outcomes for patients. However, a review of multiple studies found that they did not significantly change the risk of death or the severity of the illness. While no firm conclusions have been made, researchers are exploring these treatments for their potential to reduce severe COVID-19 complications. ^{1 6 7 8 9}

Who Is on the Research Team?

Peter Liu, MD

Principal Investigator

Ottawa Heart Institute Research Corporation

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9296362/

The effect of ACE inhibitors and ARBs on outcomes in ... Data of 896 patients with confirmed COVID-19 were analyzed in this study. In total, 18.86% (n = 169) of patients used ACEI or ARB drugs as ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10821793/

Clinical Outcomes of Angiotensin Converting Enzyme ... This review highlights the benefits of ACEi and ARB use in the treatment of symptoms associated with COVID-19 and long-term sequelae for those in recovery with ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2775280

Effect of Discontinuing vs Continuing Angiotensin ... These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19.

4. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.125.25549

Multidatabase Target Trial Emulation Studies | Hypertension Previous studies and meta-analyses concerning the comparative effectiveness of ACE inhibitors versus ARBs reported conflicting results. ... COVID- ...

5. mdpi.com mdpi.com/2543-6031/93/1/4

A Meta-Analysis of the Impact of Using Angiotensin ... Results: The results of our analysis indicated that the use of ACEIs or ARBs did not significantly influence mortality (OR = 1.10, 95% CI 0.83–1.46, p = 0.43, I ...

6. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2803515

Effect of ACE Inhibitor and ARB Initiation on Organ Support ... In this randomized clinical trial that included 779 patients, initiation of an ACE inhibitor or ARB did not improve organ support–free days.

7. ahajournals.org ahajournals.org/doi/10.1161/JAHA.120.018086

Association of Angiotensin‐Converting Enzyme Inhibitors ... Conclusions. ACE inhibitors and ARBs were not associated with COVID‐19 hospitalization or mortality. Despite early evidence for a potential ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2352906720303250

Angiotensin-converting enzyme inhibitors and ... ACEi/ARB exposure does not seem to increase the risk of having the SARS-CoV-2 infection or developing severe stages of the disease including mortality.

9. scientificarchives.com scientificarchives.com/article/evaluating-the-role-of-the-renin-angiotensin-system-in-covid-19-implications-for-ace-inhibitor-and-arb-use-during-sars-cov-2-infection

Implications for ACE Inhibitor and ARB Use During SARS ... In addition, in vitro studies showed no impact of ACE inhibitors or Angiotensin Receptor Blockers (ARB) on cell viability during SARS-CoV-2 infection. These ...