Oral Nitrite in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction (PH-HFpEF)
Primary Purpose
Pulmonary Hypertension Secondary, Heart Failure
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sodium Nitrite
Placebo Oral Capsule
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Hypertension Secondary
Eligibility Criteria
Inclusion Criteria:
Age 18 years and older
PH-HFpEF confirmed diagnosis by RHC:
- Mean Pulmonary Arterial Pressure (mPAP) ≥ 25 mmHg AND
- Pulmonary capillary wedge pressure (PWCP) ≥ 15 mmHg AND
- Transpulmonary Gradient (TPG) ≥ 12 mmHg
Exclusion Criteria:
- Age less than 18 years;
- SBP > 170 or < 110 mmHg
- DBP >95 or < 60 mmHg
- Hemoglobin A1C > 10
- Positive urine pregnancy test or breastfeeding;
- Ejection Fraction (EF) < 40%;
- Dementia
- End-stage malignancy
- Major cardiovascular event or procedure within 6 weeks prior to enrollment
- Severe valvular disease
- Known chronic psychiatric or medical conditions that may increase the risk associated with study participation in the judgment of the investigator, would make the subject inappropriate for entry into this study;
- Smoker
- Hemoglobin <9 g/dL
- Serum creatinine > 3.0 mg/dL
- Receipt of an investigational product or device, or participation in a drug research study within a period of 15 days; RHC < 2 weeks from study screening RHC unless clinically indicated
Sites / Locations
- University of Pittsburgh
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sodium Nitrite
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Pulmonary artery pressure (mPAP) during submaximal exercise as compared between placebo and nitrite
Secondary Outcome Measures
Difference in 6-minute walk test
Assessed using Borg dyspnea scale
Change in right heart catheterization (RHC) hemodynamics
RHC hemodynamic measures will be aggregated to determine if overall hemodynamic are improved over the course of treatment
Change in severity of heart failure
Determined by NT-proBNP plasma levels
Change in endurance exercise time
Change in severity of heart failure
Determined by NYHA functional classification changes
Full Information
NCT ID
NCT03015402
First Posted
January 5, 2017
Last Updated
April 7, 2023
Sponsor
Gladwin, Mark, MD
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT03015402
Brief Title
Oral Nitrite in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction
Acronym
PH-HFpEF
Official Title
Phase II Clinical Investigation of Oral Nitrite in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction (PH-HFpEF)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
October 30, 2017 (Actual)
Primary Completion Date
January 25, 2023 (Actual)
Study Completion Date
January 25, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Gladwin, Mark, MD
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The main objective of this study is to determine the clinical efficacy of oral inorganic nitrite verses placebo and the therapeutic response with regards to exercise tolerance in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).
Detailed Description
This is a single-center, 22-week double-blind, randomized placebo-controlled cross-over trial of oral nitrite on exercise capacity and hemodynamic measurements in subjects with PH-HFpEF.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension Secondary, Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sodium Nitrite
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Sodium Nitrite
Intervention Description
40 mg PO (by mouth) TID (three times each day) for 10 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Capsule
Intervention Description
Placebo capsule that is of identical size, shape, and color to experimental drug capsule PO (by mouth) TID (three times each day) for 10 weeks
Primary Outcome Measure Information:
Title
Pulmonary artery pressure (mPAP) during submaximal exercise as compared between placebo and nitrite
Time Frame
10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite).
Secondary Outcome Measure Information:
Title
Difference in 6-minute walk test
Description
Assessed using Borg dyspnea scale
Time Frame
10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)
Title
Change in right heart catheterization (RHC) hemodynamics
Description
RHC hemodynamic measures will be aggregated to determine if overall hemodynamic are improved over the course of treatment
Time Frame
10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)
Title
Change in severity of heart failure
Description
Determined by NT-proBNP plasma levels
Time Frame
10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)
Title
Change in endurance exercise time
Time Frame
10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)
Title
Change in severity of heart failure
Description
Determined by NYHA functional classification changes
Time Frame
10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 years and older
PH-HFpEF confirmed diagnosis by RHC:
Mean Pulmonary Arterial Pressure (mPAP) ≥ 25 mmHg AND
Pulmonary capillary wedge pressure (PWCP) ≥ 15 mmHg AND
Transpulmonary Gradient (TPG) ≥ 12 mmHg
Exclusion Criteria:
Age less than 18 years;
SBP > 170 or < 110 mmHg
DBP >95 or < 60 mmHg
Hemoglobin A1C > 10
Positive urine pregnancy test or breastfeeding;
Ejection Fraction (EF) < 40%;
Dementia
End-stage malignancy
Major cardiovascular event or procedure within 6 weeks prior to enrollment
Severe valvular disease
Known chronic psychiatric or medical conditions that may increase the risk associated with study participation in the judgment of the investigator, would make the subject inappropriate for entry into this study;
Smoker
Hemoglobin <9 g/dL
Serum creatinine > 3.0 mg/dL
Receipt of an investigational product or device, or participation in a drug research study within a period of 15 days; RHC < 2 weeks from study screening RHC unless clinically indicated
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Risbano, MD, MA
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Oral Nitrite in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction
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