Clinical trial NCT06053580: Repurposing Valsartan May Protect Against Pulmonary Hypertension
Official title: Repurposing Valsartan May Protect Against Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Right Heart Failure
Right Ventricular Dysfunction
Pulmonary Vascular Disorder
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-09-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, single-center, randomized placebo controlled trial of valsartan (an angiotensin receptor blocker) in adults with pulmonary arterial hypertension. The study will evaluate the safety and clinical efficacy of a 24-week course of valsartan.

Detailed description: Pulmonary arterial hypertension (PAH) is one of many conditions that put stress and strain on the right side of the heart. This stress and strain can cause right heart failure. Although there are medications to treat PAH, there are currently no medications that act directly on the heart to improve right heart function. This is different than left heart failure where one of the cornerstones of treatment is medication targeted at the heart to improve left heart function.

Valsartan is a well-tolerated and inexpensive medication that is currently used to treat hypertension and left heart failure. Preliminary results suggest that valsartan may help the right heart to adapt and strengthen when stressed instead of fail; however, these results are suggestive and not definitive. A randomized controlled trial is required to evaluate the possibility that valsartan can impact right heart function.

Participants in the study will take valsartan or placebo for 24 weeks. They will have three study visits at 0, 2, 12, and 24 weeks. These visits will add 20-30 minutes to the standard clinic visits at those time points and there will be an echocardiogram at weeks 0 and 24. The visits at weeks 2 and 12 may be completed remotely for most participants. Some participants may elect to participate in exercise testing and/or right heart catheterization at weeks 0 and 24; however, this is not required to participate in the trial.

Eligibility criteria: Inclusion Criteria:

1. Male or female, age 18 to 80
2. WHO Group 1 Pulmonary Arterial Hypertension
3. NYHA Functional Class II, III, or IV at screening (Appendix 2 for Functional Class Decision Aid)
4. Right heart catheterization within five years demonstrating a mean pulmonary arterial pressure of ≥25 mmHg, occlusion pressure of ≤15 mmHg, and resistance ≥ 3 wood units
5. Participants with a right heart catheterization within five years demonstrating a mean pulmonary arterial pressure of ≥ 25 mmHg and occlusion pressure of 15 - 20 mmHg will be considered for inclusion if the pulmonary vascular resistance ≥ 9 wood units and they are being treated with pulmonary arterial hypertension specific therapy
6. Able to walk with/without a walking aid for a distance of at least 50 meters

Exclusion Criteria:

1. Pregnant or lactating
2. Non-group 1 pulmonary hypertension or veno-occlusive disease
3. History of interstitial lung disease, unless subject has collagen vascular disease and has pulmonary function testing conducted within 12 months demonstrating a total lung capacity or vital capacity of ≥ 60 %
4. Has received or will receive an investigational drug, device, or study within 30 days or during the course of study
5. ACE-inhibitor, ARB or ARNI use within 30 days of randomization.
6. Left sided myocardial disease as evidenced by left ventricular ejection fraction \< 40%
7. 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
8. Anticipated survival less than 1 year due to concomitant disease
9. Allergy or angioedema with ACE-inhibitor use
10. Potassium \>5mEq/L or sCr \>2mg/dL at screening
11. SBP \<90mmHg at screening

Primary outcomes:
measure: Six-minute walk distance
timeFrame: 0 to 24 weeks
Secondary outcomes:
measure: Change in BNP
timeFrame: 0 to 24 weeks
measure: Change in New York Heart Association (NYHA) functional class
timeFrame: 0 to 24 weeks
measure: Change in right ventricular morphology by echocardiogram (right ventricular dilation)
timeFrame: 0 to 24 weeks
measure: Change in right ventricular morphology by echocardiogram (tricuspid annular plane systolic excursion(TAPSE))
timeFrame: 0 to 24 weeks
measure: Change in health related quality of life (emPHasis-10 questionnaire)
timeFrame: 0 to 24 weeks
measure: Frequency of escalation for PAH focused care (increased diuretics, escalating doses of pulmonary vasodilators, and/or adding additional pulmonary vasodilators)
timeFrame: 0 to 24 weeks
Other outcomes:
measure: Change in invasive hemodynamics (sub-study): Stroke Volume Index
timeFrame: 0 to 24 weeks
measure: Change in invasive hemodynamics (sub-study): Wedge pressure
timeFrame: 0 to 24 weeks
measure: Change in invasive hemodynamics (sub-study): Right Atrial pressure
timeFrame: 0 to 24 weeks
measure: Change in invasive hemodynamics (sub-study): Pulmonary Vascular Resistance
timeFrame: 0 to 24 weeks
measure: Change in Cardiopulmonary Exercise Testing (sub-study): Maximal oxygen uptake
timeFrame: 0 to 24 weeks
measure: Change in Cardiopulmonary Exercise Testing (sub-study): Ve/VCO2 slope
timeFrame: 0 to 24 weeks
measure: Change in Cardiopulmonary Exercise Testing (sub-study): Total wattage
timeFrame: 0 to 24 weeks
Locations:
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: University of Washington
name: Peter Leary, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lahm T, Hess E, Baron AE, Maddox TM, Plomondon ME, Choudhary G, Maron BA, Zamanian RT, Leary PJ. Renin-Angiotensin-Aldosterone System Inhibitor Use and Mortality in Pulmonary Hypertension: Insights From the Veterans Affairs Clinical Assessment Reporting and Tracking Database. Chest. 2021 Apr;159(4):1586-1597. doi: 10.1016/j.chest.2020.09.258. Epub 2020 Oct 5.