Combination Blood Pressure Therapy for High Blood Pressure

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt University Medical Center

Must be taking: Antihypertensives

Must not be taking: ACE inhibitors, NEPi, Lithium

Disqualifiers: Secondary hypertension, Cardiovascular disease, Diabetes, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new combination therapy, including LCZ696 (a medication for high blood pressure), can improve blood flow and enhance the release of certain substances in the body more effectively than current treatments. Participants will undergo two different treatment sequences to compare their effects. The trial seeks individuals who have experienced untreated high blood pressure on three separate occasions or have been on blood pressure medication for at least six months. As a Phase 4 trial, this research helps to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

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

The trial does not specify if you need to stop taking your current medications, but it mentions a washout period for certain conditions. It's best to discuss your specific medications with the trial coordinators.

What is the safety track record for these treatments?

Research has shown that LCZ696, also known as sacubitril/valsartan, is generally safe and well-tolerated. Long-term studies found that it significantly lowers blood pressure while remaining safe to use. In these studies, patients achieved better control of high blood pressure compared to some other treatments, with few serious side effects reported.

Valsartan, the other treatment being compared, also has a strong safety record. Studies indicate that it is safe and well-tolerated by many patients, whether used alone or with other medications. It effectively lowers blood pressure and reduces the risk of heart-related problems like stroke.

Both treatments have demonstrated a good safety profile in previous studies, making them reliable options for managing high blood pressure. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about LCZ696 for high blood pressure because it combines two active components: valsartan, a well-known angiotensin receptor blocker, and sacubitril, a neprilysin inhibitor. This combination offers a dual mechanism of action that not only blocks the hormones that tighten blood vessels but also enhances the effects of peptides that help relax them. Unlike standard treatments that mainly focus on just one pathway, LCZ696 targets both, potentially providing more effective blood pressure control. This dual approach is why researchers see promise in LCZ696 as a game-changer in managing high blood pressure.

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

This trial will compare the effectiveness of LCZ696, also known as sacubitril/valsartan, with Valsartan in managing high blood pressure. Studies have shown that LCZ696 effectively lowers blood pressure, significantly reducing it over a 24-hour period while maintaining safety and efficacy with long-term use. Valsartan, another treatment option in this trial, also effectively lowers blood pressure and has demonstrated major benefits in real-world use, proving safe for long-term use. Both treatments have strong records in managing high blood pressure. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with high blood pressure who've been on medication for at least six months or have certain levels of untreated blood pressure. Women must be postmenopausal, surgically sterilized, or using birth control. People can't join if they have a history of severe allergies to related drugs, low blood pressure, significant lung disorders, type 1 diabetes, very poor kidney function, recent steroid therapy or drug trials participation.

Inclusion Criteria

For female subjects, status post-surgical sterilization

I have high blood pressure that hasn't been treated, measured over 130 mmHg three times.

I have been postmenopausal for at least one year.

Exclusion Criteria

I have a serious lung condition.

I haven't had a serious brain condition like a stroke or seizure in the last 6 months.

My type 2 diabetes is not well-managed, with a HgbA1c over 9%.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3-4 weeks

Multiple visits for blood pressure monitoring

Treatment Phase 1

Participants receive valsartan or LCZ696 for four weeks, followed by intra-arterial infusions of bradykinin, substance P, and BNP

4 weeks

In-person visits for drug administration and monitoring

Washout

Participants undergo a three-week washout period before switching treatments

3 weeks

Treatment Phase 2

Participants receive the alternate drug (LCZ696 or valsartan) for four weeks, followed by intra-arterial infusions of bradykinin, substance P, and BNP

4 weeks

In-person visits for drug 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

• BNP
• Bradykinin
• LCZ696
• Sitagliptin
• Substance P
• Valsartan

Trial Overview The study tests whether combining an angiotensin receptor blocker (Valsartan) and neprilysin inhibitor (LCZ696) affects forearm blood flow and tissue response better than the blocker alone. It also looks at how adding a DPP4 inhibitor (Sitagliptin) changes these effects when exposed to bradykinin, substance P, and BNP.

How Is the Trial Designed?

Group I: valsartan then LCZ696 Active Control 6 Interventions

After four-week treatment with valsartan, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Then, after three-week washout and four week therapy with LCZ696, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin.

Group II: LCZ696 then valsartan Active Control 6 Interventions

After four-week treatment with LCZ696, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Then, after three-week washout and four week therapy with valsartan, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1109966625000041

Sacubitril/valsartan role in patients with resistant ... All studies reported a statistically significant reduction in blood pressure, with 24-h blood pressure reduction ranging from 15.8/6.5 to 16.6/ ...

2. ahajournals.org ahajournals.org/doi/10.1161/JAHA.122.027612

Twenty‐Four‐Hour Blood Pressure‐Lowering Efficacy of ... This post hoc analysis investigated the effects of sacubitril/valsartan on 24-hour BP in patients with mild-to-moderate hypertension and in patient subgroups ...

3. nature.com nature.com/articles/hr2016151

Long-term (52-week) safety and efficacy of Sacubitril ... Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.

4. jacc.org jacc.org/doi/10.1016/j.jacasi.2024.06.002

Efficacy and Safety of Sacubitril/Allisartan for the Treatment ... Sacubitril/allisartan is effective for the treatment of hypertension and well tolerated in Chinese patients. High blood pressure remains a major ...

5. hfsa.org hfsa.org/new-analysis-novartis-entrestor-data-shows-long-term-benefits-heart-failure-readmissions-and-total

New Analysis of Novartis' Entresto® Data Shows Long ... Novartis announced today results of a new analysis demonstrating that Entresto® (sacubitril/valsartan) tablets reduced the risk of all events.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8007371/

A Meta-Analysis on the Effect and Safety of LCZ696 in the ... The pooled WMD results showed that LCZ696 had a more pronounced antihypertensive effect compared with the results of ARBs treatment.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6251522/

Systolic blood pressure, cardiovascular outcomes and efficacy ... For example, the sacubitril/valsartan versus enalapril hazard ratio for the primary endpoint was 0.88 (95%CI 0.74–1.06) in patients with a baseline SBP <110 ...

8. journals.lww.com journals.lww.com/jhypertension/abstract/2022/06001/efficacy_and_safety_of_sacubitril_valsartan.628.aspx

EFFICACY AND SAFETY OF SACUBITRIL/VALSARTAN ... Among Asians, LCZ696 is strongly associated with better hypertension control against olmesartan. However, its efficacy in reducing MACE is not as robust.

9. sciencedirect.com sciencedirect.com/science/article/pii/S2772374724002254

Efficacy and Safety of Sacubitril/Allisartan for the Treatment ... Notably, our study showed that nighttime blood pressure reductions were prominently greater with sacubitril/allisartan than with olmesartan in Chinese patients ...