Repurposing Valsartan May Protect Against Pulmonary Hypertension

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Valsartan 40 mg
  Valsartan 40mg twice daily for 24 weeks.
• Препарат Placebo
  Placebo twice daily for 24 weeks.

Первичные конечные точки

• Six-minute walk distance [Срок оценки: 0 to 24 weeks]

Вторичные конечные точки (6)

• Change in BNP [Срок оценки: 0 to 24 weeks]
• Change in New York Heart Association (NYHA) functional class [Срок оценки: 0 to 24 weeks]
• Change in right ventricular morphology by echocardiogram (right ventricular dilation) [Срок оценки: 0 to 24 weeks]
• Change in right ventricular morphology by echocardiogram (tricuspid annular plane systolic excursion(TAPSE)) [Срок оценки: 0 to 24 weeks]
• Change in health related quality of life (emPHasis-10 questionnaire) [Срок оценки: 0 to 24 weeks]
• Frequency of escalation for PAH focused care (increased diuretics, escalating doses of pulmonary vasodilators, and/or adding additional pulmonary vasodilators) [Срок оценки: 0 to 24 weeks]

Критерии участия

Критерии включения

• Male or female, age 18 to 80
• WHO Group 1 Pulmonary Arterial Hypertension
• NYHA Functional Class II, III, or IV at screening (Appendix 2 for Functional Class Decision Aid)
• 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
• 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
• Able to walk with/without a walking aid for a distance of at least 50 meters

Критерии исключения

• Pregnant or lactating
• Non-group 1 pulmonary hypertension or veno-occlusive disease
• 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 %
• Has received or will receive an investigational drug, device, or study within 30 days or during the course of study
• ACE-inhibitor, ARB or ARNI use within 30 days of randomization.
• Left sided myocardial disease as evidenced by left ventricular ejection fraction < 40%
• 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
• Anticipated survival less than 1 year due to concomitant disease
• Allergy or angioedema with ACE-inhibitor use
• Potassium >5mEq/L or sCr >2mg/dL at screening
• SBP <90mmHg at screening

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Washington Medical Center — Seattle

Публикации

• 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. PMID 33031831

Идентификаторы

NCT: NCT06053580 · STUDY00018685 · R61HL167848

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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