Losartan for Cardiovascular Disease

Overseen by Mehrdad Arjomandi, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of California, San Francisco

Must not be taking: ACE inhibitors, ARBs, NSAIDs, Potassium diuretics

Disqualifiers: Pregnancy, Cardiovascular disease, Pulmonary disease, Renal insufficiency, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a double-blind randomized placebo-controlled crossover clinical trial of efficacy and safety of an FDA-approved angiotensin receptor blocker (losartan) to improve cardiopulmonary outcomes in individuals with pre-Chronic Obstructive Pulmonary Disease (COPD) due to prolonged exposure to secondhand tobacco smoke.

Will I have to stop taking my current medications?

The trial requires that you do not currently use certain medications like ACE inhibitors, ARBs, NSAIDs regularly, or potassium supplements. If you are on these medications, you may need to stop them to participate.

What evidence supports the effectiveness of the drug Losartan for cardiovascular disease?

Research shows that Losartan, a drug used to treat high blood pressure and heart failure, can improve heart function and reduce the risk of death in heart failure patients. In studies, patients taking Losartan had a lower chance of dying compared to those not taking the drug. ^{1 2 3 4 5}

Is losartan safe for humans?

Losartan is generally considered safe for humans, with studies showing it is well tolerated and has a low incidence of side effects. Common side effects include headache, dizziness, and fatigue, but these are often similar to those experienced with a placebo. Serious side effects are rare, and it is better tolerated than many other blood pressure medications. ^{2 6 7 8 9}

What makes the drug Losartan unique for treating cardiovascular disease?

Losartan is unique because it is an angiotensin II receptor blocker (ARB) that selectively targets the AT1 receptor, providing cardiovascular benefits with a low incidence of side effects. It is well-absorbed orally and converted in the liver to a more potent form, offering effective once-daily dosing for heart failure and hypertension. ^{1 2 3 8 10}

Research Team

Mehrdad Arjomandi, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Adults over 40 with a history of secondhand tobacco smoke exposure for at least 5 years, like former flight attendants or casino workers. They should have smoked less than one pack-year and not smoked for the past 20 years. Participants must be able to consent and follow the study plan but can't join if they're pregnant, breastfeeding, planning pregnancy, have certain heart conditions or blood pressure issues, drug use history (except occasional marijuana), are on specific medications like ACE inhibitors or ARBs, or have severe kidney problems.

Inclusion Criteria

I have never smoked or was only a light smoker.

I have not smoked for 20 years or more.

I have smoked less than 1 pack of cigarettes a year in my life.

Exclusion Criteria

I am currently taking medication that helps my body retain potassium.

Blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic while standing or sitting

I have a heart condition that requires ACE inhibitor or ARB treatment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either placebo or losartan for 4 weeks, followed by a 2-week washout period, then crossover to the alternate treatment for another 4 weeks

10 weeks

Multiple visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Losartan (Angiotensin Receptor Blocker)
• Placebo (Drug)

Trial Overview The trial is testing Losartan's effectiveness in improving heart and lung health against a placebo in people who've been exposed to secondhand smoke but don't yet have COPD. It's a double-blind study where neither participants nor researchers know who gets the real medicine versus the placebo until after results are collected.

Participant Groups

Group I: Placebo then Losartan Experimental Treatment 2 Interventions

Placebo tablets will be administered for the first 4 weeks followed by a washout period of 2 weeks. After the washout period has been completed, losartan tablets will be administered for the next 4 weeks.

Group II: Losartan then Placebo Experimental Treatment 2 Interventions

Losartan tablets will be administered for the first 4 weeks followed by a washout period of 2 weeks. After the washout period has been completed, placebo tablets will be administered for the next 4 weeks.

Losartan is already approved in Canada for the following indications:

Approved in Canada as Cozaar for:

• Hypertension
• Diabetic nephropathy
• Heart failure

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Suresh Gunasekaran

University of California, San Francisco

Chief Executive Officer since 2022

MBA from Southern Methodist University

Dr. Lukejohn Day

University of California, San Francisco

Chief Medical Officer

MD from Stanford University School of Medicine

Flight Attendant Medical Research Institute

Collaborator

Trials

13

Recruited

2,700+

Findings from Research

Losartan is a selective angiotensin II type 1 (AT(1)) receptor antagonist that is well-absorbed and converted in the liver to a more potent metabolite, E3174, which has a significantly higher affinity for the AT(1) receptor, leading to effective antihypertensive effects over a 24-hour period with once-daily dosing.

Clinical experience shows that losartan has excellent tolerability in over 6 million patients treated for hypertension, and emerging data suggest it may improve survival in heart failure patients compared to traditional treatments like captopril.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure. Dickstein, K., Timmermans, P., Segal, R.[2019]

Losartan potassium, an angiotensin II receptor antagonist, shows significant haemodynamic benefits in patients with heart failure, based on extensive clinical trials.

The drug is well tolerated with a low incidence of adverse effects related to kidney function, making it a safe option for treating hypertension and heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Losartan in heart failure: preclinical experiences and initial clinical outcomes. Sweet, CS., Rucinska, EJ.[2019]

Losartan/hydrochlorothiazide (HCTZ) is an effective fixed-dose combination therapy for hypertension, providing greater blood pressure reduction than either medication alone, and is particularly beneficial for patients with severe hypertension and left ventricular hypertrophy (LVH).

In the LIFE study, losartan-based therapy demonstrated a lower incidence of cardiovascular events and new-onset diabetes compared to atenolol, highlighting its safety and efficacy in reducing stroke risk and improving overall cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Losartan/Hydrochlorothiazide: a review of its use in the treatment of hypertension and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy. Keating, GM.[2021]

Losartan is an effective angiotensin II receptor antagonist used to manage hypertension and heart failure, demonstrating significant antihypertensive activity.

The review provides comprehensive details on losartan's physical and chemical properties, stability, pharmacokinetics, and various analytical methods for its assessment, ensuring a thorough understanding of the drug's profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Losartan: Comprehensive Profile. Al-Majed, AR., Assiri, E., Khalil, NY., et al.[2015]

A meta-analysis of 1,896 heart failure patients showed that losartan significantly reduced all-cause mortality, with a death rate of 3.12% in losartan groups compared to 6.35% in control groups, indicating a potential survival benefit.

Losartan was well tolerated and improved hemodynamic and symptomatic outcomes in heart failure patients, but the authors recommend larger studies to confirm its mortality benefits compared to ACE inhibitors due to the small number of deaths and short follow-up in the analyzed studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of observed mortality data from all-controlled, double-blind, multiple-dose studies of losartan in heart failure. Losartan Heart Failure Mortality Meta-analysis Study Group. Sharma, D., Buyse, M., Pitt, B., et al.[2019]

Losartan, an angiotensin II receptor antagonist, significantly reduced systolic blood pressure by 15.9% and diastolic blood pressure by 20.3% in a study of 15 patients with an average age of 48.9.

The treatment with Losartan showed good tolerability, with no significant adverse effects on blood cell production, carbohydrate and lipid metabolism, or kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of moderate or severe arterial hypertension with losartan. Dimitrova, A., Todorova, M., Bianov, K., et al.[2020]

Losartan, a medication for hypertension, was well-tolerated in approximately 2000 patients, showing a lower incidence of adverse effects compared to other antihypertensive drugs, particularly ACE inhibitors.

The most common side effects reported with losartan were headache and dizziness, but overall, it had a better safety profile with only 2.3% of patients withdrawing due to adverse effects, and no significant safety concerns were noted across different demographic groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of losartan compared with atenolol, felodipine and angiotensin converting enzyme inhibitors. Goldberg, AI., Dunlay, MC., Sweet, CS.[2019]

A validated reversed-phase high-performance thin-layer chromatography method has been developed for testing losartan potassium in COZAAR tablets, demonstrating sensitivity and reliability.

This new method offers an effective alternative to traditional HPLC stability testing, potentially improving the quality control processes for losartan potassium formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of losartan and its degradates in COZAAR tablets by reversed-phase high-performance thin-layer chromatography. McCarthy, KE., Wang, Q., Tsai, EW., et al.[2019]

In a study involving approximately 2,900 hypertensive patients, losartan was found to have a good safety and tolerability profile, with common side effects like headache and dizziness occurring at similar rates to placebo.

Losartan was better tolerated than other antihypertensive medications, with low rates of discontinuation due to adverse effects (2.3% for losartan monotherapy) and no significant safety concerns across different demographic groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. Goldberg, AI., Dunlay, MC., Sweet, CS.[2019]

A 64-year-old woman developed severe pustular vasculitis likely caused by losartan, an antihypertensive medication, indicating a rare but serious side effect of this drug.

Withdrawal of losartan and treatment with corticosteroids led to the resolution of the skin lesions, highlighting the importance of monitoring for adverse reactions in patients taking this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Severe pustular and polymorphous vasculitis caused by losartan]. Piérard Franchimont, C., Henry, F., Piérard, GE.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Losartan in heart failure: preclinical experiences and initial clinical outcomes. [2019]

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

Losartan/Hydrochlorothiazide: a review of its use in the treatment of hypertension and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Losartan: Comprehensive Profile. [2015]

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

Meta-analysis of observed mortality data from all-controlled, double-blind, multiple-dose studies of losartan in heart failure. Losartan Heart Failure Mortality Meta-analysis Study Group. [2019]

6. Bulgaria pubmed.ncbi.nlm.nih.gov

Treatment of moderate or severe arterial hypertension with losartan. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of losartan compared with atenolol, felodipine and angiotensin converting enzyme inhibitors. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Determination of losartan and its degradates in COZAAR tablets by reversed-phase high-performance thin-layer chromatography. [2019]

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

Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. [2019]

10. France pubmed.ncbi.nlm.nih.gov

[Severe pustular and polymorphous vasculitis caused by losartan]. [2022]