Losartan for Cardiovascular Disease

Overseen By Mehrdad Arjomandi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests losartan, a medication, to determine if it can help individuals exposed to significant secondhand tobacco smoke avoid developing chronic lung problems. The study compares losartan with a placebo (a harmless pill with no active drug) to measure effects on heart and lung health. Participants will alternate between the placebo and losartan, allowing researchers to compare results. This trial may suit non-smokers or those who smoked minimally in the past and have worked in smoky environments, such as certain flight attendants or casino workers. As a Phase 4 trial, losartan is already FDA-approved and proven effective; this research aims to understand how it benefits more patients.

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 is the safety track record for losartan?

Research shows that losartan is generally safe for people. The FDA has approved this drug, which is commonly used to treat high blood pressure and protect the kidneys. Studies have found that most people tolerate losartan well.

In clinical trials, side effects were usually mild. Some individuals might experience dizziness or a stuffy nose, but these effects are not serious and often resolve over time. Serious side effects are rare. Losartan has been used safely in many studies, including those focused on heart and kidney health.

Overall, research supports the safety of losartan, but discussing any concerns with a doctor before starting a new treatment is always advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Losartan for cardiovascular disease because it targets the angiotensin II receptor, which helps relax blood vessels and lower blood pressure. Unlike many standard treatments that might focus on different pathways or involve complex combinations, Losartan's mechanism offers a direct approach to reducing strain on the heart. Additionally, its established safety profile from treating hypertension makes it a promising option for broader cardiovascular applications, potentially offering more tailored treatment strategies for patients.

What is the effectiveness track record for losartan in improving cardiopulmonary outcomes in individuals with pre-COPD?

Research has shown that losartan, an FDA-approved medication, can lower the risk of heart problems. In studies, losartan reduced heart-related issues by 25% compared to atenolol. It also alleviates symptoms like shortness of breath in people with heart failure. Losartan blocks certain signals that cause blood vessels to tighten, allowing them to relax and improve blood flow. In this trial, participants will receive either losartan or a placebo in different sequences to evaluate its effects. These benefits suggest that losartan might improve heart and lung function in people at risk of COPD from secondhand smoke exposure. ^{4 6 7 8 9}

Who Is on the Research Team?

Mehrdad Arjomandi, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Losartan
• Placebo

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Cozaar for:

• Hypertension
• Diabetic nephropathy
• Stroke prevention in hypertension and left ventricular hypertrophy

Approved in European Union as Cozaar for:

• Hypertension
• Diabetic nephropathy
• Heart failure

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+

Flight Attendant Medical Research Institute

Collaborator

Trials

13

Recruited

2,700+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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, 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2888651/

Cardiovascular Effects of Losartan and Its Relevant Clinical ... This article reviews direct and indirect cardiovascular effects of losartan on the heart and blood vessels.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/12243636/

Effects of losartan on cardiovascular morbidity and ... The main outcome was reduced by 25% with losartan compared with atenolol, 25.1 vs 35.4 events per 1000 patient-years (relative risk [RR], 0.75; 95% confidence ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa011161

Effects of Losartan on Renal and Cardiovascular Outcomes ... In particular, the risk of end-stage renal disease was reduced by 28 percent with losartan during an average follow-up of 3.4 years. Extrapolating from the ...

4. ahajournals.org ahajournals.org/doi/10.1161/01.cir.91.3.691

Losartan in Heart Failure | Circulation Symptoms of exertional dyspnea more often improved than worsened after 12 weeks in the 50-mg (52% improved and 9% worsened) and 25-mg (48% and 10%, respectively) ...

5. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/195319

Effects of Losartan on Cardiovascular Morbidity and ... The main outcome was reduced by 25% with losartan compared with atenolol, 25.1 vs 35.4 events per 1000 patient-years (relative risk [RR], 0.75; ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK526065/

Losartan - StatPearls - NCBI Bookshelf Safety, tolerability, and outcomes of losartan use in patients hospitalized with SARS-CoV-2 infection: A feasibility study. PLoS One. 2020 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12084478/

A Randomized Comparative Trial of Losartan/Chlorthalidone ... The safety results indicate a favorable profile for both losartan/chlorthalidone and losartan/hydrochlorothiazide treatments. Adverse events ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/losartan-and-hydrochlorothiazide-oral-route/description/drg-20062877

Losartan and hydrochlorothiazide (oral route) - Side effects ... If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/020386s062lbl.pdf

COZAAR® (losartan potassium) tablets - accessdata.fda.gov The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and ...