Blood Pressure Management Strategies for High Blood Pressure

Overseen by Elaine Ku, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: University of California, San Francisco

Must be taking: Anti-hypertensives

Disqualifiers: Pregnancy, Drug abuse, Cognitive impairment, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a pilot randomized controlled trial which will test the effect of 3 different anti-hypertensive agents and 3 different strategies of engaging young adults in home blood pressure monitoring on blood pressure control, with secondary outcomes focused on quality of life and adverse events.

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.

What data supports the effectiveness of the drug Amlodipine for managing high blood pressure?

Research shows that Amlodipine is effective in reducing blood pressure, with a study indicating it achieved a mean reduction in systolic blood pressure of -20.7 mmHg. However, it was associated with higher rates of peripheral edema compared to other treatments. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Amlodipine is generally safe for humans, with most side effects being mild, such as swelling (edema). It is well tolerated by elderly patients and does not require dosage changes for those with kidney issues. Chlorthalidone, when combined with other medications like atenolol, is also well tolerated and effective for managing high blood pressure. ^{6 7 8 9 10}

How does the drug combination of Amlodipine, Chlorthalidone, and Losartan differ from other high blood pressure treatments?

This drug combination is unique because it combines three different types of medications: Amlodipine, a calcium channel blocker that relaxes blood vessels; Chlorthalidone, a diuretic that helps remove excess fluid; and Losartan, an angiotensin receptor blocker that lowers blood pressure by blocking a hormone that tightens blood vessels. This multi-faceted approach can be more effective for patients who need multiple mechanisms to control their high blood pressure. ^{3 5 9 11 12}

Research Team

Elaine Ku, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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 am between 18 and 40 years old.

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.

Trial Timeline

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

Treatment Details

Interventions

• Amlodipine (Calcium Channel Blocker)
• Chlorthalidone (Diuretic)
• Home BP monitoring with cuffed device (Device)
• Home BP monitoring with cuffed device + BP patch (Device)
• Home BP monitoring with cuffed device + BP watch (Device)
• Losartan (Angiotensin II Receptor Blocker)

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.

Participant Groups

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 Canada, Japan, China, Switzerland for the following indications:

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+

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

Findings from Research

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]

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 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 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]

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]

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 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]

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]

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]

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 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]

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]

References

1. Sweden pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of the combination valsartan/hydrochlorothiazide compared with amlodipine in a mild-to-moderately hypertensive Brazilian population. [2021]

2. India 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. [2021]

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

Chlorthalidone versus hydrochlorothiazide for the treatment of hypertension in older adults: a population-based cohort study. [2014]

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

Mortality and morbidity during and after the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. [2021]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Antihypertensive Efficacy of Fixed Combination Azilsartan Medoxomil / Chlorthalidone in Patients With Uncontrolled Arterial Hypertension]. [2019]

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

Azilsartan medoxomil/chlorthalidone: a new fixed-dose combination antihypertensive. [2017]

7. England 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. [2013]

8. England 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. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

Controlled clinical trial of cadralazine as a second-step drug in the treatment of hypertension. [2019]

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

The safety of amlodipine. [2019]

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

Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil. [2017]

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

Valsartan combination therapy in the management of hypertension - patient perspectives and clinical utility. [2021]