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Repurposing Valsartan May Protect Against Pulmonary Hypertension (REVAMP-PH)

Primary Purpose

Pulmonary Arterial Hypertension, Right Heart Failure, Right Ventricular Dysfunction

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Valsartan 40 mg
Placebo
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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

Sites / Locations

  • University of Washington Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Valsartan

Placebo

Arm Description

Valsartan 40mg capsule taken twice daily for 24 weeks.

Placebo capsule taken twice daily for 24 weeks.

Outcomes

Primary Outcome Measures

Six-minute walk distance
To determine whether valsartan increases six-minute walk distance at 24 weeks in men and women with pulmonary arterial hypertension.

Secondary Outcome Measures

Change in BNP
To determine whether valsartan reduces BNP at 24 weeks
Change in New York Heart Association (NYHA) functional class
To determine whether valsartan improves New York Heart Association (NYHA) functional class at 24 weeks (NYHA Functional Class is a score from 1 to 4 where higher scores connote worse health-related impairment)
Change in right ventricular morphology by echocardiogram (right ventricular dilation)
To determine whether valsartan improves right ventricular morphology at 24 weeks including improved right ventricular dilation
Change in right ventricular morphology by echocardiogram (tricuspid annular plane systolic excursion(TAPSE))
To determine whether valsartan improves right ventricular morphology at 24 weeks including improved TAPSE
Change in health related quality of life (emPHasis-10 questionnaire)
To determine whether valsartan improves health related quality of life as estimated by the emPHasis- 10 score (Each item on the emPHasis-10 questionnaire is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end; EmPHasis-10 scores range from 0 to 50 with higher scores indicating worse quality of life)
Frequency of escalation for PAH focused care (increased diuretics, escalating doses of pulmonary vasodilators, and/or adding additional pulmonary vasodilators)
To determine whether valsartan decreases the need to escalate PAH focused care (increased diuretics, escalating doses of pulmonary vasodilators, and/or adding an additional pulmonary vasodilator)

Full Information

First Posted
September 7, 2023
Last Updated
September 13, 2023
Sponsor
University of Washington
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT06053580
Brief Title
Repurposing Valsartan May Protect Against Pulmonary Hypertension
Acronym
REVAMP-PH
Official Title
Repurposing Valsartan May Protect Against Pulmonary Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 1, 2024 (Anticipated)
Primary Completion Date
July 1, 2027 (Anticipated)
Study Completion Date
July 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension, Right Heart Failure, Right Ventricular Dysfunction, Pulmonary Vascular Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Valsartan
Arm Type
Experimental
Arm Description
Valsartan 40mg capsule taken twice daily for 24 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo capsule taken twice daily for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Valsartan 40 mg
Other Intervention Name(s)
Diovan
Intervention Description
Valsartan 40mg twice daily for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo twice daily for 24 weeks.
Primary Outcome Measure Information:
Title
Six-minute walk distance
Description
To determine whether valsartan increases six-minute walk distance at 24 weeks in men and women with pulmonary arterial hypertension.
Time Frame
0 to 24 weeks
Secondary Outcome Measure Information:
Title
Change in BNP
Description
To determine whether valsartan reduces BNP at 24 weeks
Time Frame
0 to 24 weeks
Title
Change in New York Heart Association (NYHA) functional class
Description
To determine whether valsartan improves New York Heart Association (NYHA) functional class at 24 weeks (NYHA Functional Class is a score from 1 to 4 where higher scores connote worse health-related impairment)
Time Frame
0 to 24 weeks
Title
Change in right ventricular morphology by echocardiogram (right ventricular dilation)
Description
To determine whether valsartan improves right ventricular morphology at 24 weeks including improved right ventricular dilation
Time Frame
0 to 24 weeks
Title
Change in right ventricular morphology by echocardiogram (tricuspid annular plane systolic excursion(TAPSE))
Description
To determine whether valsartan improves right ventricular morphology at 24 weeks including improved TAPSE
Time Frame
0 to 24 weeks
Title
Change in health related quality of life (emPHasis-10 questionnaire)
Description
To determine whether valsartan improves health related quality of life as estimated by the emPHasis- 10 score (Each item on the emPHasis-10 questionnaire is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end; EmPHasis-10 scores range from 0 to 50 with higher scores indicating worse quality of life)
Time Frame
0 to 24 weeks
Title
Frequency of escalation for PAH focused care (increased diuretics, escalating doses of pulmonary vasodilators, and/or adding additional pulmonary vasodilators)
Description
To determine whether valsartan decreases the need to escalate PAH focused care (increased diuretics, escalating doses of pulmonary vasodilators, and/or adding an additional pulmonary vasodilator)
Time Frame
0 to 24 weeks
Other Pre-specified Outcome Measures:
Title
Change in invasive hemodynamics (sub-study): Stroke Volume Index
Description
To determine whether valsartan increases stroke volume index at 24 weeks
Time Frame
0 to 24 weeks
Title
Change in invasive hemodynamics (sub-study): Wedge pressure
Description
Exploratory: To explore whether valsartan is associated with differences in wedge pressure at 24 weeks
Time Frame
0 to 24 weeks
Title
Change in invasive hemodynamics (sub-study): Right Atrial pressure
Description
Exploratory: To explore whether valsartan is associated with differences in right atrial pressure at 24 weeks
Time Frame
0 to 24 weeks
Title
Change in invasive hemodynamics (sub-study): Pulmonary Vascular Resistance
Description
Exploratory: To explore whether valsartan is associated with differences in pulmonary vascular resistance at 24 weeks
Time Frame
0 to 24 weeks
Title
Change in Cardiopulmonary Exercise Testing (sub-study): Maximal oxygen uptake
Description
To determine whether valsartan increases maximal oxygen uptake in individuals with pulmonary arterial hypertension at 24 weeks
Time Frame
0 to 24 weeks
Title
Change in Cardiopulmonary Exercise Testing (sub-study): Ve/VCO2 slope
Description
Exploratory: To explore whether valsartan decreases the Ve/VCO2 slope in individuals with pulmonary arterial hypertension over 24 weeks
Time Frame
0 to 24 weeks
Title
Change in Cardiopulmonary Exercise Testing (sub-study): Total wattage
Description
Exploratory: To explore whether valsartan increases total achieved wattage in individuals with pulmonary arterial hypertension over 24 weeks
Time Frame
0 to 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laurie Hogl, RRT
Phone
206.543.8334
Email
lalnaser@uw.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Nancy Liston, MS
Phone
206.543.8334
Email
nmliston@uw.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Leary, MD, PhD
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33031831
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.
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Repurposing Valsartan May Protect Against Pulmonary Hypertension

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