Blood Pressure Management Strategies for High Blood Pressure

Overseen By Elaine Ku, MD, MAS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must be taking: Anti-hypertensives

Disqualifiers: Pregnancy, Drug abuse, Cognitive impairment, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests three medications to determine their effectiveness in managing high blood pressure. It also examines how different home blood pressure tracking methods can enhance control and quality of life. The trial targets young adults (ages 18-40) diagnosed with high blood pressure or with readings indicating it. Participants will use either Amlodipine, Chlorthalidone, or Losartan, along with various home monitoring tools such as watches, patches, or cuffs. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

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

Research shows that amlodipine, chlorthalidone, and losartan are generally safe and well-tolerated for managing high blood pressure.

Amlodipine relaxes blood vessels, making it easier for blood to flow. Studies have found it safe for both adults and children, with mild side effects like leg swelling and dizziness.

Chlorthalidone, a diuretic often called a "water pill," helps the body remove extra fluid and salt, which lowers blood pressure. Most people handle it well, but it can sometimes cause dehydration or low blood pressure if not monitored.

Losartan blocks a substance that tightens blood vessels. Research indicates it is generally safe, with rare side effects like dizziness or a stuffy nose.

These medications are part of a trial to evaluate their effectiveness with different home blood pressure monitoring methods. Testing at this stage usually indicates a good safety profile in earlier studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for high blood pressure because they incorporate innovative home monitoring techniques. Unlike traditional methods that use a single device, these treatments pair standard medications like amlodipine, chlorthalidone, and losartan with modern monitoring devices, including watches and patches. These advanced devices could allow for continuous, real-time monitoring of blood pressure, potentially leading to better management and personalized treatment. This approach aims to empower patients with more accessible and convenient ways to track their health, which could enhance treatment effectiveness and adherence.

What evidence suggests that this trial's treatments could be effective for high blood pressure?

Research has shown that amlodipine, one of the treatments in this trial, lowers blood pressure and reduces the risk of strokes and heart attacks. Studies have found that people taking amlodipine often achieve blood pressure levels around 130/80, considered well-controlled. Chlorthalidone, another treatment option in this trial, is known for its long-lasting effect, providing better blood pressure control throughout the day compared to some other medications, which greatly benefits heart health. Losartan, also studied in this trial, effectively lowers blood pressure, especially when taken daily, and works even better when combined with other medications. Each of these treatments has a proven history of managing high blood pressure and improving heart health. ^{1 6 7 8 9}

Who Is on the Research Team?

Elaine Ku, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for young adults aged 18-40 with high blood pressure, who are not pregnant, don't have severe hypertension or kidney issues, and aren't abusing substances. Participants should be stable (not marginally housed), able to follow the study protocol without cognitive impairments, and not involved in other trials that could affect their blood pressure.

Inclusion Criteria

I have high blood pressure or am on medication for it.

My blood pressure is often higher than 130/80 mmHg at the clinic and above 125/80 mmHg at home.

Exclusion Criteria

Institutionalized individuals or prisoners

You are currently using illegal drugs or drinking alcohol excessively.

I do not have cognitive issues preventing me from joining the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of three anti-hypertensive agents and engage in home blood pressure monitoring using different devices

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amlodipine
• Chlorthalidone
• Home BP monitoring with cuffed device
• Home BP monitoring with cuffed device + BP patch
• Home BP monitoring with cuffed device + BP watch
• Losartan

Trial Overview

The trial tests three anti-hypertensive medications: Chlorthalidone, Amlodipine, and Losartan. It also examines three home BP monitoring methods: a cuffed device alone or combined with either a BP patch or watch. The goal is to see which combination best controls blood pressure while considering quality of life.

How Is the Trial Designed?

Group I: losartan 12.5 mg daily + home BP monitoring with watch Experimental Treatment 2 Interventions

Use of at least the minimum dose of this agent and use of a home BP monitoring device only + a watch for BP monitoring

Group II: chlorthalidone 12.5 mg daily + home BP monitoring with watch Experimental Treatment 2 Interventions

Use of at least the minimum dose of this agent and use of a home BP monitoring device only + a watch for BP monitoring

Group III: amlodipine 2.5 mg daily + home BP monitoring with watch Experimental Treatment 2 Interventions

Use of at least the minimum dose of this agent and use of a home BP monitoring device only + a watch for BP monitoring

Group IV: amlodipine 2.5 mg daily + home BP monitoring with patch Experimental Treatment 2 Interventions

Use of at least the minimum dose of this agent and use of a home BP monitoring device only + a patch for BP monitoring

Group V: Losartan 12.5 mg daily + home BP monitoring with patch Experimental Treatment 2 Interventions

Use of at least the minimum dose of this agent and use of a home BP monitoring device only + a patch for BP monitoring

Group VI: Losartan 12.5 mg daily + home BP monitoring with cuffed device Experimental Treatment 2 Interventions

Use of at least the minimum dose of losartan and use of a home BP monitoring cuffed device only for BP monitoring

Group VII: Chlorthalidone 12.5 mg daily + home BP monitoring with patch Experimental Treatment 2 Interventions

Use of at least the minimum dose of this agent and use of a home BP monitoring device only + a patch for BP monitoring

Group VIII: Chlorthalidone 12.5 mg + Home BP monitoring with cuffed device Experimental Treatment 2 Interventions

Use of at least the minimum dose of chlorthalidone and use of a home BP monitoring device for BP monitoring

Group IX: Amlodipine 2.5 mg + Home BP monitoring with cuffed device Active Control 2 Interventions

Use of at least the minimum dose of amlodipine and use of a home BP monitoring device for BP monitoring

Amlodipine is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Norvasc for:

• Hypertension
• Angina
• Variant angina

Approved in European Union as Norvasc for:

• Hypertension
• Coronary artery disease
• Variant angina

Approved in Canada as Norvasc for:

• Hypertension
• Angina

Approved in Japan as Norvasc for:

• Hypertension
• Angina pectoris

Approved in China as Norvasc for:

• Hypertension

Approved in Switzerland as Norvasc for:

• Hypertension
• Coronary artery disease

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a study of 373 patients with essential hypertension, the combination of valsartan and hydrochlorothiazide (HCTZ) was found to be as effective as amlodipine in reducing 24-hour ambulatory blood pressure, with similar reductions in systolic and diastolic blood pressure.

The valsartan/HCTZ combination had significantly lower rates of adverse events, particularly peripheral edema, compared to amlodipine, indicating it may be a better-tolerated treatment option for hypertensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of the combination valsartan/hydrochlorothiazide compared with amlodipine in a mild-to-moderately hypertensive Brazilian population. Franco, RJ., Goldflus, S., McQuitty, M., et al.[2021]

Angiotensin receptor blockers (ARBs), specifically valsartan/hydrochlorothiazide and amlodipine/valsartan, are effective in lowering blood pressure and are well tolerated in a diverse range of hypertensive patients, including those with severe hypertension and other complicating health conditions.

These ARB combinations not only help achieve better blood pressure control but also enhance patient compliance through single-pill formulations, making them a practical choice for individuals requiring multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valsartan combination therapy in the management of hypertension - patient perspectives and clinical utility. Nash, DT., McNamara, MS.[2021]

Both telmisartan/amlodipine and telmisartan/hydrochlorothiazide effectively reduced blood pressure in Japanese patients with uncontrolled hypertension, with similar results after 12 weeks of treatment.

Telmisartan/hydrochlorothiazide had a quicker onset of blood pressure-lowering effects and caused significant changes in serum potassium and uric acid levels, but both treatments were safe with no severe adverse effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of telmisartan/amlodipine and telmisartan/hydrochlorothiazide in the treatment of Japanese patients with uncontrolled hypertension: the TAT-Kobe study. Kondo, K., Toh, R., Ishida, T., et al.[2018]

Amlodipine, assessed in a study of 4227 subjects, showed a slightly higher incidence of side effects compared to placebo, primarily due to well-tolerated edema, but had a favorable safety profile compared to beta-blockers like atenolol and nadolol, with severe side effects being about half as common.

Amlodipine is well tolerated in elderly patients and does not negatively affect serum creatinine, urate, or glucose levels, making it a safe option for managing hypertension without the adverse effects seen with some other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of amlodipine. Osterloh, I.[2019]

In a study of 29,873 older adults, chlorthalidone did not show a significant advantage over hydrochlorothiazide in reducing adverse cardiovascular events or deaths, with similar rates of these outcomes between the two medications.

However, patients taking chlorthalidone were significantly more likely to experience electrolyte imbalances, particularly hypokalemia, indicating a safety concern with its use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chlorthalidone versus hydrochlorothiazide for the treatment of hypertension in older adults: a population-based cohort study. Dhalla, IA., Gomes, T., Yao, Z., et al.[2014]

In a study of 609 participants with stage 2 primary hypertension, chlorthalidone combined with azilsartan medoxomil resulted in a greater reduction in systolic blood pressure compared to hydrochlorothiazide combined with azilsartan, with a mean difference of -5.6 mm Hg.

Chlorthalidone also led to a higher percentage of participants achieving target blood pressure (64.1% vs 45.9%) without significant differences in safety or adverse events between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil. Bakris, GL., Sica, D., White, WB., et al.[2017]

In a study of 25 patients with uncontrolled arterial hypertension, a fixed combination of azilsartan medoxomil and chlorthalidone effectively lowered blood pressure, with 88% of participants reaching target blood pressure levels after 12 weeks.

The treatment started at a dose of 40/12.5 mg per day and could be increased to 40/25 mg per day if necessary, demonstrating the combination's flexibility and potential efficacy in managing hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antihypertensive Efficacy of Fixed Combination Azilsartan Medoxomil / Chlorthalidone in Patients With Uncontrolled Arterial Hypertension]. Kobalava, ZD., Villevalde, SV., Kulakov, VV.[2019]

In a study involving 282 stage I hypertensive patients, the combination of low-dose chlorthalidone (6.25 mg) and atenolol (25 mg) was found to be effective in reducing blood pressure, showing similar efficacy to higher doses of atenolol alone and atenolol combined with amlodipine.

The study reported no serious adverse events, indicating that the low-dose chlorthalidone and atenolol combination is safe, potentially allowing for broader use in hypertension treatment while minimizing metabolic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of low-dose chlorthalidone (6.25 mg) + atenolol combination in stage I hypertensive patients: a multicenter, randomized, controlled study. Pareek, A., Karnik, N., Salagre, SB., et al.[2013]

In a study involving 20 hypertensive patients, both the new vasodilator cadralazine and the diuretic chlorthalidone effectively reduced blood pressure when combined with atenolol, showing no significant difference in efficacy between the two treatments.

Cadralazine was found to better compensate for the heart rate decrease caused by atenolol compared to chlorthalidone, suggesting potential hemodynamic advantages that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled clinical trial of cadralazine as a second-step drug in the treatment of hypertension. Catalano, M., Parini, J., Romano, M., et al.[2019]

The combination of azilsartan medoxomil and chlorthalidone significantly reduces blood pressure more effectively than other combinations, such as olmesartan medoxomil/hydrochlorothiazide, in four randomized controlled trials involving hypertensive patients.

This combination treatment is generally well tolerated, with only minor increases in serum creatinine and no significant impact on potassium levels, making it a safe option for managing hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azilsartan medoxomil/chlorthalidone: a new fixed-dose combination antihypertensive. Pierini, D., Anderson, KV.[2017]

In a study of 100 Indian hypertensive patients who did not reach target blood pressure with telmisartan and hydrochlorothiazide, switching to a combination of telmisartan (40 mg) and chlorthalidone (12.5 mg) resulted in significant reductions in both systolic and diastolic blood pressure after 4 weeks.

The combination therapy was effective, achieving target blood pressure in 24% of patients for systolic and 19% for diastolic pressure, with no significant adverse events reported, indicating it is a safe and well-tolerated option for managing hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Antihypertensive Efficacy of Chlorthalidone and Telmisartan in Indian Hypertensive Patients who were Uncontrolled with Hydrochlorothiazide and Telmisartan Combination-A Prospective and an Open Label Study. Sagarad, SV., Kerure, SB., Kumar S, C., et al.[2021]

In a large trial with 32,804 participants aged 55 and older, chlorthalidone was found to be as effective as amlodipine and lisinopril in preventing cardiovascular mortality over a follow-up period of 8 to 13 years.

However, amlodipine was associated with a higher risk of heart failure and lisinopril with increased stroke mortality compared to chlorthalidone, indicating that diuretics may be a safer long-term option for managing hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mortality and morbidity during and after the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Cushman, WC., Davis, BR., Pressel, SL., et al.[2021]

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