Blood Pressure Treatment for High Blood Pressure

(LOADED-BP Trial)

Recruiting at 2 trial locations

Overseen By Adam Gepner

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must be taking: Antihypertensives

Must not be taking: Betablockers

Disqualifiers: Recent CVD, Stroke, Cancer, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 months

228 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you must be willing to have your blood pressure medications adjusted according to the study protocol.

What data supports the effectiveness of the blood pressure treatment algorithm for high blood pressure?

Research shows that using a combination of medications, like olmesartan, amlodipine, and hydrochlorothiazide, is effective in controlling high blood pressure, especially when a single drug isn't enough. This approach is recommended in treatment guidelines and has been shown to help more patients reach their blood pressure goals. ^{1 2 3 4 5}

Is the blood pressure treatment generally safe for humans?

Blood pressure treatments can reduce the risk of heart-related problems, but they may also cause serious side effects, especially with intensive treatment. It's important to balance the benefits and risks, as excessive treatment can lead to harm. ^{6 7 8 9 10}

How does the blood pressure treatment algorithm differ from other treatments for high blood pressure?

This treatment is unique because it uses a specific sequence of medications, starting with a fixed-dose combination of lisinopril and hydrochlorothiazide, which is maximized before adding amlodipine, and then spironolactone as a fourth option. This structured approach has achieved high control rates in many patients. ^{2 7 11 12 13}

What is the purpose of this trial?

Hypertension is a common and treatable disorder that remains the leading preventable cause of heart disease. Blood pressure treatment relies mainly on upper arm blood pressure readings and ignores blood vessel physiology and underlying individual genetic information. Older Veterans with hypertension are less likely to be treated to goal blood pressure because there are conflicting recommendations for what constitutes "optimal" in older adults. The investigators have developed a novel way to non-invasively assess the components of blood vessel stiffness that is related to blood pressure (load-dependent stiffness). This project will generate new knowledge about how different blood pressure treatment goals (intensive vs standard) impact different components of arterial stiffness and if these differences can be explained through genetic analysis. Results from this project will offer the VA an updated blueprint for personalizing blood pressure care in older adults, ultimately improving cardiovascular health.

Research Team

Adam Gepner

Principal Investigator

William S. Middleton Memorial Veterans Hospital, Madison, WI

Eligibility Criteria

This trial is for older adults with high blood pressure, focusing on Veterans. Participants should have hypertension and be interested in how different treatment goals affect arterial stiffness. The study seeks to personalize care by considering vessel physiology and genetics.

Inclusion Criteria

I am over 60, have high blood pressure, or take up to 4 medications for it.

Veterans with documented SBP readings on 2 or more office visits of 140 mmHg or average home blood pressure readings of 135 mmHg

I am willing to follow the study's blood pressure treatment plan and undergo specific heart health tests.

Exclusion Criteria

I do not have HIV, a current infection or fever above 38°C, nor have I been hospitalized in the last 4 weeks.

Participants with factors limiting adherence to study interventions or follow-up such as active substance abuse, plans to move outside study catchment areas within 12 months, or history of poor medication adherence or clinic no-shows

My blood pressure is usually below 110 mmHg when standing.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either intensive or standard blood pressure treatment, with primary outcomes assessed at baseline and after 3, 6, and 12 months

12 months

Regular visits for medication titration and assessment at baseline, 3, 6, and 12 months

Follow-up

Participants are monitored for safety outcomes such as hypotension, acute kidney injury, and falls

12 months

Treatment Details

Interventions

• Blood pressure treatment algorithm

Trial Overview The trial tests a novel blood pressure treatment algorithm that takes into account the stiffness of blood vessels related to aging. It compares intensive versus standard treatment goals and includes genetic analysis to tailor care for cardiovascular health.

Participant Groups

Group I: Intensive BP targets Experimental Treatment 1 Intervention

\<120 mmHg systolic)

Group II: Standard blood pressure targets Active Control 1 Intervention

\<140 mmHg systolic

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

The Lundquist Institute

Collaborator

Trials

1

Recruited

230+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Nashville VA Medical Center

Collaborator

Trials

4

Recruited

770+

Birmingham, Alabama VA Medical Center

Collaborator

Trials

4

Recruited

530+

VA Tennessee Valley Health Care System

Collaborator

Trials

5

Recruited

1,400+

Findings from Research

Combination therapy is often necessary for hypertensive patients to achieve blood pressure targets, especially when monotherapy is insufficient, and it can provide enhanced efficacy and reduced side effects due to lower doses.

The fixed combination of olmesartan medoxomil and hydrochlorothiazide has been approved for hypertension treatment, leveraging the benefits of both an angiotensin receptor blocker and a diuretic to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olmesartan medoxomil plus hydrochlorothiazide for treating hypertension. Barrios, V., Escobar, C.[2015]

Despite the proven effectiveness of antihypertensive therapy, many patients do not achieve their target blood pressure, indicating a need for improved treatment strategies.

Enhancing blood pressure control through better patient assessment, caregiver support, and specialist referrals could significantly benefit patients, especially those with resistant hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guest Editorial Challenges in Resistant Hypertension. Kahan, T.[2023]

In a review of 70 randomized controlled trials involving nearly 256,000 participants, blood pressure-lowering treatments significantly reduced the risk of major cardiovascular events by 24%, but also led to an 89% increase in treatment discontinuations due to adverse events.

The analysis revealed that while greater reductions in blood pressure (BP) were associated with more significant cardiovascular benefits, they also resulted in a disproportionately higher number of patients discontinuing treatment, especially when systolic blood pressure (SBP) was lowered below 130 mmHg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of blood pressure lowering treatment in hypertension: 8. Outcome reductions vs. discontinuations because of adverse drug events - meta-analyses of randomized trials. Thomopoulos, C., Parati, G., Zanchetti, A.[2018]

In the SPRINT trial, patients with higher baseline cardiovascular disease (CVD) risk benefited more from intensive blood pressure treatment, while those with lower risk experienced more harm than benefit, highlighting the importance of risk stratification in treatment decisions.

The study found that the number needed to treat to prevent primary outcomes decreased significantly with higher CVD risk, while the number needed to harm for serious adverse events increased, indicating a favorable benefit-to-harm ratio for intensive treatment in higher-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Cardiovascular Risk on the Relative Benefit and Harm of Intensive Treatment of Hypertension. Phillips, RA., Xu, J., Peterson, LE., et al.[2022]

The prevalence of hypertension diagnosis among nursing home residents increased significantly from 75.2% to 85.1% over a decade, indicating a growing recognition of high blood pressure in this population.

Despite high treatment rates (80.3% treated) and good control of blood pressure (80.1% with average BP <140/90 mmHg), certain high-risk groups, such as Black and Hispanic residents and those with diabetes or renal disease, still had elevated blood pressure levels, highlighting the need for targeted interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in blood pressure diagnosis, treatment, and control among VA nursing home residents, 2007-2018. Odden, MC., Li, Y., Graham, LA., et al.[2023]

References

1. Chile pubmed.ncbi.nlm.nih.gov

[Antihypertensive efficacy of monotherapy in increasing doses versus therapy associated in low doses]. [2013]

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

Efficacy and safety of a stepped-care regimen using olmesartan medoxomil, amlodipine and hydrochlorothiazide in patients with moderate-to-severe hypertension: an open-label, long-term study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Olmesartan medoxomil plus hydrochlorothiazide for treating hypertension. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Guest Editorial Challenges in Resistant Hypertension. [2023]

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

Where are we with the management of hypertension? From science to clinical practice. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of blood pressure lowering treatment in hypertension: 8. Outcome reductions vs. discontinuations because of adverse drug events - meta-analyses of randomized trials. [2018]

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

Commentary in support of a highly effective hypertension treatment algorithm. [2021]

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

Impact of Cardiovascular Risk on the Relative Benefit and Harm of Intensive Treatment of Hypertension. [2022]

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

Trends in blood pressure diagnosis, treatment, and control among VA nursing home residents, 2007-2018. [2023]

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

Efficacy of a brief multifactorial adherence-based intervention in reducing blood pressure: a randomized clinical trial. [2020]

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

Multiple drug therapy in the treatment of essential hypertension. [2005]

12. Germany pubmed.ncbi.nlm.nih.gov

[Non-pharmacological and pharmacological treatment of arterial hypertension: current situation]. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Low blood pressure and cardiovascular events in diabetic patients with coronary artery disease after revascularization: the CREDO-Kyoto registry cohort-1. [2021]