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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different blood pressure treatment goals can improve heart health in older adults. Researchers examine how treating high blood pressure affects blood vessel stiffness and whether genetics play a role. Participants will be randomly assigned to either a standard or more intensive blood pressure target. Veterans over 60 with high blood pressure who are open to trying different treatment goals might be a good fit. The trial aims to develop a better plan for managing blood pressure in older adults, especially veterans. As an unphased trial, it offers participants the chance to contribute to valuable research that could lead to improved heart health strategies for older adults.

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 prior data suggests that this blood pressure treatment algorithm is safe?

Research shows that intensive blood pressure treatments can be effective and safe for many people. Studies have found that this approach significantly reduces the risk of major heart problems compared to standard treatments. However, intensive blood pressure control might cause side effects, such as a slightly higher chance of dizziness or fainting.

The evidence suggests that while the benefits, like fewer heart problems, often outweigh the risks, individual health needs should be considered. Many people handle the treatment well, but some might feel uncomfortable. Always consult healthcare providers to determine the best approach for your specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to manage high blood pressure through different blood pressure targets. Unlike the usual approach that aims for a systolic blood pressure of less than 140 mmHg, this trial includes an experimental arm targeting a more intensive level of below 120 mmHg. The hope is to find out whether aiming for these lower targets can significantly reduce the risk of heart-related issues or provide other health benefits. This could potentially shift the guidelines for treating high blood pressure, offering a more precise and possibly more effective strategy.

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

This trial will compare two approaches to blood pressure management: standard and intensive blood pressure targets. Studies have shown that more intensive treatment of high blood pressure can significantly reduce the risk of heart problems and even death. Research suggests that aiming for a systolic blood pressure of less than 120, as tested in the intensive BP targets arm of this trial, leads to fewer heart issues compared to higher targets. A review of multiple studies found that maintaining this number below 130 also reduces the risk of serious heart-related events. Additionally, more aggressive blood pressure control is generally considered more beneficial than harmful. These findings indicate that lowering blood pressure further can greatly benefit heart health, especially in older adults. ^{6 7 8 9 10}

Who Is on the Research Team?

Adam Gepner

Principal Investigator

William S. Middleton Memorial Veterans Hospital, Madison, WI

Are You a Good Fit for This Trial?

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/HYP.0000000000000249

2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ ... The focus of this clinical practice guideline is to create a living, working document updating current knowledge in the field of high blood ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6343947/

Intensive Blood Pressure Treatment for Resistant ... The present study demonstrated that intensive BP treatment was significantly associated with a decreased risk of cardiovascular events and death in patients ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2111437

Trial of Intensive Blood-Pressure Control in Older Patients ... A meta-analysis showed that a systolic blood-pressure target of less than 130 mm Hg was associated with a decreased risk of cardiovascular ...

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01391-1/abstract

Benefit–harm trade-offs of intensive blood pressure control ... Overall, intensive blood pressure control showed a favourable benefit–harm profile, with a net benefit of 1·14 (95% CrI 1·03–1·25), using ...

5. aafp.org aafp.org/pubs/afp/issues/2022/1200/practice-guidelines-aafp-hypertension-full-guideline.html

Blood Pressure Targets in Adults With Hypertension Purpose: To review the evidence and provide clinical recommendations for appropriate blood pressure treatment targets for adults with hypertension.

6. jacc.org jacc.org/doi/10.1016/j.jacc.2025.06.045

Intensive Blood Pressure Control in Older Patients With ... After a median follow-up of 6.11 years, the mean SBP was 127.9 mm Hg in the sustained intensive treatment group and 129.5 mm Hg in the delayed ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12327570/

Impact of Intensive Blood Pressure Control Versus Standard ... Intensive blood pressure control significantly decreased the odds of MACE (RR: 0.80, 95% CI: 0.73-0.88) compared to standard management. Notable ...

8. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.036820

Intensive Blood Pressure Strategy on Cardiovascular ... The intensive blood pressure control strategy (<130/80 mm Hg) reduced incident cardiovascular diseases in patients with hypertension and ...

9. acc.org acc.org/latest-in-cardiology/journal-scans/2025/09/19/16/45/intensive-bp-control

Intensive BP Control Provides Net Benefit Between Fewer ... Notably, intensive BP control was associated with a 1.73% absolute risk reduction in cardiovascular disease (number needed to treat = 58) and a ...

10. jwatch.org jwatch.org/na59186/2025/09/11/comparing-risks-and-benefits-intensive-blood-pressure

Comparing the Risks and Benefits of Intensive Blood ... Intensive BP control resulted in fewer cardiovascular events than standard BP control (absolute reduction, 1.7%) but more treatment-related ...