Valsartan for Pulmonary Hypertension

(REVAMP-PH Trial)

Overseen By Nancy Liston, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: ACE inhibitors, ARBs, ARNIs

Disqualifiers: Pregnancy, Non-group 1 hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests valsartan, a medication typically used for blood pressure, to determine its effectiveness for pulmonary arterial hypertension (a type of high blood pressure affecting the lungs). Researchers aim to assess valsartan's safety and effectiveness over 24 weeks. Participants will receive either valsartan or a placebo (a harmless pill resembling the treatment) for comparison. The trial seeks adults diagnosed with pulmonary arterial hypertension who frequently struggle with physical activities like walking and have had specific heart pressure levels measured in the past five years. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking ACE-inhibitors, ARBs, or ARNIs at least 30 days before joining. If you're on these medications, you'll need to stop them before participating.

Is there any evidence suggesting that valsartan is likely to be safe for humans?

Studies have shown that valsartan, a drug commonly used for high blood pressure and heart failure, is generally well-tolerated. Research indicates that it can improve heart function under stress and may reduce lung pressures associated with pulmonary hypertension.

Regarding safety, the FDA has approved valsartan for treating high blood pressure and heart failure, indicating its safety for these conditions. While specific safety data for pulmonary hypertension is still under investigation, existing research has not identified major safety issues with valsartan in similar uses. As with any medication, some individuals might experience side effects, so discussing concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary hypertension?

Most treatments for pulmonary hypertension, like endothelin receptor antagonists and phosphodiesterase-5 inhibitors, work by relaxing blood vessels or reducing blood pressure in the lungs. But Valsartan works differently, targeting the renin-angiotensin-aldosterone system to block the actions of a hormone called angiotensin II, which can lead to blood vessel narrowing. Researchers are excited about Valsartan because it offers a new mechanism of action that might improve symptoms and outcomes for patients who don't respond well to current therapies.

What evidence suggests that valsartan might be an effective treatment for pulmonary hypertension?

Research has shown that valsartan, a type of medication, might help with pulmonary hypertension, a condition affecting the lungs and heart. In this trial, participants will receive either valsartan or a placebo. One study examined past cases and found that valsartan lowered pressure in the lung arteries of patients with heart failure, which relates to the condition under study. Another study suggested that valsartan might help the right side of the heart handle stress better. Some research also indicates that using valsartan with another drug can improve heart function and lower lung pressure in similar conditions. While these results are promising, more research is needed to confirm valsartan's effectiveness specifically for pulmonary arterial hypertension. ^{1 2 4 6 7}

Who Is on the Research Team?

Peter Leary, MD, PhD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

Adults aged 18-80 with WHO Group 1 Pulmonary Arterial Hypertension, able to walk at least 50 meters, and have specific heart catheterization results. Excluded are those with very low blood pressure or kidney function issues, expected short survival due to other diseases, certain lung conditions, recent investigational drug use, left heart disease, pregnancy/lactation, non-group 1 pulmonary hypertension or allergy to similar medications.

Inclusion Criteria

My heart tests show high lung blood pressure and I'm on specific treatment for it.

I can walk at least 50 meters, with or without help.

You had a heart test within the past five years that showed high pressure in the arteries of your lungs, low pressure in the veins of your lungs, and resistance in the blood vessels.

Exclusion Criteria

You are not expected to live for more than 1 year due to another serious illness.

Any other clinically significant illness or abnormal laboratory values (measured during the Screening period) that, in the opinion of the Investigator, might put the subject at risk of harm during the study or might adversely affect the interpretation of the study data

My heart's left side is weak, with an ejection fraction below 40%.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive valsartan or placebo for 24 weeks. Visits occur at weeks 0, 2, 12, and 24, with echocardiograms at weeks 0 and 24. Some visits may be completed remotely.

24 weeks

4 visits (in-person/remote)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Valsartan

Trial Overview

The trial is testing the safety and effectiveness of Valsartan (40 mg), an angiotensin receptor blocker for treating pulmonary arterial hypertension over a course of 24 weeks. Participants will be randomly assigned to receive either Valsartan or a placebo in this Phase 2 study.

How Is the Trial Designed?

Group I: Valsartan Experimental Treatment 1 Intervention

Valsartan 40mg capsule taken twice daily for 24 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo capsule taken twice daily for 24 weeks.

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

Approved in European Union as Diovan for:

• Hypertension
• Heart failure
• Left ventricular dysfunction

Approved in United States as Diovan for:

• Hypertension
• Heart failure

Approved in Canada as Diovan for:

• Hypertension
• Heart failure

Approved in Japan as Valsartan for:

• Hypertension
• Heart failure

Approved in China as Valsartan for:

• Hypertension

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In the VALIANT trial, valsartan was found to be as effective as captopril in reducing mortality and cardiovascular issues in patients with heart failure or left ventricular systolic dysfunction after a heart attack, indicating its efficacy in high-risk populations.

Valsartan was generally well tolerated, and combining it with captopril did not provide extra benefits and was less tolerated, suggesting that valsartan could be a preferable option for post-myocardial infarction treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valsartan: a review of its use in patients with heart failure and/or left ventricular systolic dysfunction after myocardial infarction. Croom, KF., Keating, GM.[2018]

Valsartan effectively reduces blood pressure in children and adolescents with hypertension, showing significant dose-dependent reductions in both systolic and diastolic blood pressure after just 2 weeks of treatment in a study involving participants aged 6-16 years.

In a comparison trial, valsartan was found to be as effective as enalapril in lowering blood pressure over 12 weeks, with similar rates of patients achieving target blood pressure levels, and it was well tolerated over a treatment period of up to 52 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valsartan: in children and adolescents with hypertension. Croxtall, JD.[2021]

In a study of 500 patients with pulmonary arterial hypertension, initial combination therapy with ambrisentan and tadalafil significantly reduced the risk of clinical failure events by 50% compared to monotherapy, indicating its efficacy as a first-line treatment.

The combination therapy also led to greater improvements in key health markers, such as a 67.2% reduction in N-terminal pro-brain natriuretic peptide levels and a median increase of 48.98 meters in 6-minute walk distance, although it was associated with more frequent side effects like peripheral edema and headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. Galiè, N., Barberà, JA., Frost, AE., et al.[2022]

In a study of 28 Chinese patients with pulmonary hypertension, ambrisentan significantly improved exercise capacity, as measured by the six-minute walk distance, increasing from 372 m to 443 m after 12 weeks (P = 0.000).

The treatment also led to improvements in the World Health Organization functional class and a reduction in NT-proBNP levels, indicating better heart function, while showing no significant changes in liver function, suggesting it is well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of ambrisentan therapy in Chinese patients with pulmonary hypertension]. Chen, FD., Zhou, DX., Di, RM., et al.[2016]

Bosentan is the first oral dual endothelin receptor antagonist approved for treating pulmonary arterial hypertension, significantly improving exercise capacity and symptoms in patients.

Large-scale studies have confirmed bosentan's long-term safety and tolerability, making it a crucial treatment option for pulmonary arterial hypertension and potentially other endothelin-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bosentan: a dual endothelin receptor antagonist. Rubin, LJ., Roux, S.[2019]

At a dose of 80 mg/day, valsartan effectively lowers blood pressure with a side effect profile similar to ACE inhibitors, but with a lower incidence of cough.

Valsartan does not show a clear advantage over losartan and has not been proven to prevent complications related to high blood pressure, making its use less validated compared to other antihypertensive medications like diuretics and beta-blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valsartan. Just a second-line antihypertensive drug. [2018]

Valsartan is an effective angiotensin receptor blocker that helps treat hypertension and is comparable in efficacy to ACE inhibitors for patients with myocardial infarction and heart failure.

In patients with congestive heart failure who cannot tolerate ACE inhibitors, valsartan not only reduces mortality but also decreases hospitalizations related to heart failure when used alongside ACE inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valsartan: the past, present and future. Køber, L., Torp-Pedersen, C.[2009]

The combination of sacubitril/valsartan (LCZ 696) and bosentan significantly reduces pulmonary pressures and improves right ventricular function in rat models of severe pulmonary hypertension, demonstrating superior efficacy compared to either drug alone.

This dual therapy not only protects against vascular remodeling but also increases levels of beneficial markers like atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP), suggesting a mechanism that enhances cardiovascular health in the context of pulmonary arterial hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additive protective effects of sacubitril/valsartan and bosentan on vascular remodelling in experimental pulmonary hypertension. Chaumais, MC., Djessas, MRA., Thuillet, R., et al.[2022]

In a study of Japanese patients with pulmonary arterial hypertension (PAH), macitentan showed significantly higher treatment persistence compared to ambrisentan and bosentan after its approval in 2015, with median persistence of 18 months for macitentan versus 6 and 8 months for ambrisentan and bosentan, respectively.

The analysis included real-world data from 2008 to 2020, involving 153 patients on bosentan, 51 on ambrisentan before macitentan's approval, and 331 on macitentan after approval, indicating that macitentan may be a more effective long-term treatment option for PAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Treatment Persistence and Adherence to Endothelin Receptor Antagonists Among Patients with Pulmonary Arterial Hypertension in Japan: A Real-World Administrative Claims Database Study. Omura, J., Makanji, Y., Tanabe, N., et al.[2023]

Valsartan, an AT1 receptor blocker, significantly reduced the development of pulmonary hypertension (PH) in both rats and mice, as shown by lower right ventricular pressure and less lung vascular remodeling.

The study revealed that valsartan works by inhibiting smooth muscle cell proliferation and reducing the expression of factors involved in extracellular matrix remodeling, suggesting it could be an effective treatment for PH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents. Lu, Y., Guo, H., Sun, Y., et al.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10233066/

The emerging role of sacubitril/valsartan in pulmonary ...

A retrospective cohort study discovered that patients with HFrEF exhibited a significant decrease in pulmonary artery systolic pressure (PASP) ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06053580

Repurposing Valsartan May Protect Against Pulmonary ...

Preliminary results suggest that valsartan may help the right heart to adapt and strengthen when stressed instead of fail; however, these results are suggestive ...

3.

ahajournals.org

ahajournals.org/doi/10.1161/JAHA.121.024449

Effect of Sacubitril/Valsartan on the Right Ventricular ...

This meta‐analysis verified that S/V could improve right ventricular performance and pulmonary hypertension in heart failure with reduced ejection fraction.

4.

jacc.org

jacc.org/doi/10.1016/j.jaccas.2025.104827

Successful Management of HFpEF-Related Pulmonary ...

Significant symptom improvement and normalized pulmonary pressures were noted after treatment with sacubitril-valsartan and a sodium-glucose ...

5.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1001121

Effect of Valsartan on the Incidence of Diabetes and ...

Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9288803/

Sacubitril/valsartan affects pulmonary arterial pressure in ...

Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF–PH, independent of loop diuretic management, together with improvement in ...

7.

frontiersin.org

frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.1055330/full

The efficacy and safety of Sacubitril/Valsartan on ...

Sac/Val is approved for hypertension and chronic heart failure with reduced ejection fraction. We unexpectedly found that Sac/Val reduced PASP ...