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Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF (INDIE-HFpEF)

Primary Purpose

Heart Failure

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nebulized Sodium Nitrite
Placebo
Sponsored by
Adrian Hernandez
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥ 40 years
  2. Symptoms of dyspnea (NYHA class II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea
  3. EF ≥ 50% as determined on imaging study within 12 months of enrollment with no change in clinical status suggesting potential for deterioration in systolic function

  4. One of the following :

    • Previous hospitalization for HF with radiographic evidence (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) of pulmonary congestion or
    • Catheterization documented elevated filling pressures at rest (PCWP ≥15 or LVEDP ≥18) or with exercise (PCWP ≥25) or
    • Elevated NT-proBNP (>400 pg/ml) or BNP(>200 pg/ml) or
    • Echo evidence of diastolic dysfunction/elevated filling pressures manifest by medial E/e' ratio≥15 and/or left atrial enlargement and chronic treatment with a loop diuretic for signs or symptoms of heart failure
  5. Heart failure is primary factor limiting activity as indicated by answering # 2 to the following question:

My ability to be active is most limited by:

  1. Joint, foot, leg, hip or back pain
  2. Shortness of breath and/or fatigue and/or chest pain
  3. Unsteadiness or dizziness
  4. Lifestyle, weather, or I just don't like to be active

6. Peak VO2 ≤75% predicted with peak respiratory exchange ratio≥1.0 CPET Normal Values for Peak VO2* Criteria (ml/kg/min) 7. No chronic nitrate therapy or not using intermittent sublingual nitroglycerin (requirement for >1 SL nitroglycerin per week) within last 7 days 8. No daily use of phosphodiesterase 5 inhibitors or soluble guanylyl cyclase activators and willing to withhold prn use of phosphodiesterase 5 inhibitors for duration of study 9. Ambulatory (not wheelchair / scooter dependent) 10. Body size allows wearing of the accelerometer belt as confirmed by ability to comfortably fasten the test belt provided for the screening process (belt designed to fit persons with BMI 20-40 kg/m2 but belt may fit some persons outside this range) 11. Willingness to wear the accelerometer belt for the duration of the trial 12. Willingness to provide informed consent

Exclusion Criteria:

  1. Recent (< 1 month) hospitalization for heart failure
  2. Ongoing requirement for PDE5 inhibitor, organic nitrate or soluble guanylyl cyclase activators
  3. Hemoglobin (Hgb) < 8.0 g/dl within 90 days prior to randomization
  4. GFR < 20 ml/min/1.73 m2 within 90 days prior to randomization
  5. Systolic blood pressure < 115 mmHg seated or < 90 mmHg standing just prior to test dose
  6. Resting HR > 110 just prior to test dose
  7. Previous adverse reaction to the study drug which necessitated withdrawal of therapy
  8. Significant chronic obstructive pulmonary disease thought to contribute to dyspnea
  9. Ischemia thought to contribute to dyspnea
  10. Documentation of previous EF < 45%
  11. Acute coronary syndrome within 3 months defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g., troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)
  12. PCI, coronary artery bypass grafting, or new biventricular pacing within past 3 months
  13. Primary hypertrophic cardiomyopathy
  14. Infiltrative cardiomyopathy (amyloid)
  15. Constrictive pericarditis or tamponade
  16. Active myocarditis
  17. Complex congenital heart disease
  18. Active collagen vascular disease
  19. More than mild aortic or mitral stenosis
  20. Intrinsic (prolapse, rheumatic) valve disease with moderate to severe or severe mitral, tricuspid or aortic regurgitation
  21. Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, INR > 1.7 in the absence of anticoagulation treatment
  22. Terminal illness (other than HF) with expected survival of less than 1 year
  23. Regularly (> 1x per week) swims or does water aerobics
  24. Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months.
  25. Inability to comply with planned study procedures
  26. Pregnancy or breastfeeding mothers

Sites / Locations

  • Emory University School of Medicine
  • Northwestern University
  • Johns Hopkins Hospital
  • Tufts Medical Center
  • Massachusetts General Hospital
  • Brigham and Women's Hospital
  • Boston V.A. Healthcare System
  • Mayo Clinic
  • University of Missouri Health System
  • V.A St. Louis Health Care System
  • Washington University School of Medicine
  • Stony Brook University Medical Center
  • Duke University Medical Center
  • University Hospitals Cleveland Medical Center
  • Metro Health System
  • Cleveland Clinic Foundation
  • Abington Memorial Hospital
  • University of Pennsylvania Health System
  • Jefferson Medical College
  • The University of Vermont - Fletcher Allen Health Care

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AIR001 Crossover to Placebo

Placebo crossover to AIR001

Arm Description

Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.

Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.

Outcomes

Primary Outcome Measures

Peak VO2
The primary endpoint will be the peak VO2 after 4 weeks treatment with inorganic nitrite as compared to the peak VO2 after 4 weeks treatment with placebo as assessed by cardiopulmonary exercise testing (CPET) performed at peak drug levels.

Secondary Outcome Measures

Average Arbitrary Accelerometer Units (AAU)
Average arbitrary accelerometer units (AAU) during at least 14 days and up to 21 days of the maximally tolerated dose of study drug (from 28 days post Study Visit 1 until Study Visit 2 and from 28 days post Study Visit 2 until Study Visit 3). An arbitrary accelerometer unit is calculated within the accelerometer device that is worn by the patient and represents level of activity based upon patient movement. Higher values indicate more movement. Zero indicates no movement.
Medial E/e' Ratio as Measured by Echocardiography Core Lab
To evaluate whether AIR001 improves Medial E/e' ratio (the ratio between early mitral inflow velocity and mitral annular early diastolic velocity for diastolic evaluation) in comparison to placebo.
Left Atrial Volume Index as Measured by Echocardiography
To evaluate whether AIR001 improves Left atrial volume index in comparison to placebo.
Pulmonary Artery Systolic Pressure as Measured by Echocardiography
To evaluate whether AIR001 improves pulmonary artery systolic pressure in comparison to placebo.
Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Score
To evaluate whether AR001 improves quality of life in comparison to placebo. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcomes measure for patients with heart failure. It consists of 23 items, is comprised of 7 clinically relevant scales (Symptom Frequency, Symptom Burden, Symptom Stability, Physical Limitation, Social Limitation, Quality of Life, and Self-Efficacy), and yields 3 summary scores (Clinical Summary, Total Symptom, and Overall Summary Scores). Scale and summary scores range between 0 and 100, with higher scores indicating better health status (eg, better functioning, fewer symptoms, better quality of life). Higher values of the overall KCCQ score are considered to be better than lower values.
N-terminal Pro-B-type Natriuretic Peptide Level (NT-proBNP)
Evaluate whether AIR001 improves natriuretic peptide levels in comparison to placebo
NYHA (New York Heart Association) Class
To evaluate whether AR001 improves NYHA Class in comparison to placebo. NYHA class was measured at the end of each phase. The site physician evaluated the patient based upon the criteria for NYHA class I-IV used by the American Heart Association. NYHA functional classification provides a way of classifying the extent of heart failure. Class I (least severe): No limitation of physical activity; Class II: Slight limitation of physical activity; Class III: Marked limitation of physical activity; Class IV (most severe): Unable to carry on any physical activity without discomfort.
Patient Preference for AIR001 Treatment at the End of Study
Self-reported participant preference for study period 1 (Phase 1) vs. study period 2 (Phase 2)
VE/VCO2 Slope (Ventilatory Efficiency) as Provided by Cardiopulmonary Exercise Testing Core Lab
To evaluate whether ARI001 in comparison to placebo improves ventilator efficiency as measured by Slope of Ve/VCO2 during study drug administration. The Ve/VCO2 slope is defined as the slope of the linear relationship between ventilation and carbon dioxide output and is a measure of the velocity.
VO2 at Ventilatory Threshold (Submaximal Exercise Capacity) as Provided by Cardiopulmonary Exercise Testing Core Lab
To evaluate whether ARI001 in comparison to placebo improves submaximal exercise capacity as measured by VO2 (rate of oxygen consumption measured during incremental exercise) at ventilatory threshold during study drug administration.

Full Information

First Posted
April 8, 2016
Last Updated
February 18, 2019
Sponsor
Adrian Hernandez
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Aires Pharmaceuticals, Inc., University of Vermont, Université de Montréal, Mayo Clinic, Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02742129
Brief Title
Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF
Acronym
INDIE-HFpEF
Official Title
Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
August 10, 2016 (Actual)
Primary Completion Date
December 13, 2017 (Actual)
Study Completion Date
December 27, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Adrian Hernandez
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Aires Pharmaceuticals, Inc., University of Vermont, Université de Montréal, Mayo Clinic, Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A randomized, double-blind, placebo-controlled crossover study to assess the effect of inorganic nitrite (NO2) on aerobic capacity (peak VO2) after four weeks of dosing. Approximately 100 participants will be enrolled in this 2*2 crossover study.
Detailed Description
Screen potential HFpEF patients for eligibility criteria and interest Study Visit 1 • Initiate consent process and obtain written informed consent. Confirm with the participant that HF symptoms are the primary limitation to activity. If so, they proceed to CPET screening. If not, they are considered a screen fail. Obtain baseline bloods *- CBC, complete chemistry panel, biomarkers, biorepository and genetics (if agreed to participate) . Obtain CPET to verify patient eligibility peak VO2 ≤ 75% predicted and RER ≥ 1.0 (within 3 days prior to randomization) and establish baseline value. Qualifying patients perform additional baseline studies: history, assess NYHA class, physical exam, ECG, and KCCQ. Open label, single-dose run-in where patient receives maximal dose (80 mg) inhaled inorganic nitrite. Patients who do not tolerate the run-in are considered screen failures. Randomize qualifying patients. Dispense phase-1 study drug, nebulizers and accelerometers Participants take no study drug for two weeks (baseline). Participants take 46 mg study drug at a minimum of 4 hours apart, 3 times a day, during active part of the day for 7 days. Participants take 80 mg study drug at a minimum of 4 hours apart, 3 times a day, during active part of the day until returning for study visit 2 (at least 42 days but up to 49 days post-baseline visit). If side effects develop, participants can down-titrate to the previous dose. Participants are called frequently to reinforce study procedures and assess compliance. Study Visit 2 (42-49 Days Post Study Visit 1) • Participant holds study drug on day of visit. Review history, assess NYHA class, perform physical exam and KCCQ. Obtain blood draws ** - CBC, complete chemistry panel, biomarkers, biorepository (if agreed to participate). Obtain limited echocardiogram **. Perform CPET with Study Drug administered immediately before starting the CPET (primary endpoint). Change out accelerometer and dispense phase-2 study drug. Participants take no study drug for two weeks (washout). Participants take 46 mg study drug at a minimum of 4 hours apart, 3 times a day, during active part of the day for 7 days. Participants take 80 mg study drug at a minimum of 4 hours apart, 3 times a day, during active part of the day until returning for study visit 3 (at least 42 but up to 49 days after study visit 2). If side effects develop Participants can down-titrate to the previously tolerated dose. Participants are called frequently to reinforce study procedures and assess compliance. Study Visit 3 (42-49 Days Post Study Visit 2) • Participant holds study drug on day of visit. • Review history, assess NYHA class, perform physical exam and KCCQ Obtain blood draws** - CBC, complete chemistry panel, biomarkers, biorepository (if agreed to participate). Obtain limited echocardiogram**. Perform CPET with Study Drug administered immediately before starting the CPET (primary endpoint). Return accelerometer and phase-2 study drug. End of study drug (phase out). Phone Visit and End of Study (14 Days Post Study Visit 3) • A final phone visit is conducted to assess for adverse events. *Visit 1: baseline blood draw needs to be completed prior to the CPET (if this is not feasible, then they cannot be obtained for at least 3 hours post the CPET and prior to the run-in test dose). **Visit 2 and Visit 3: blood draws and limited echo need to be obtained prior to study drug administration (if this is not feasible, then it cannot be obtained for at least 3 hours post study drug administration)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AIR001 Crossover to Placebo
Arm Type
Experimental
Arm Description
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug Nebulized Sodium Nitrite (AIR001) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Placebo instead of AIR001.
Arm Title
Placebo crossover to AIR001
Arm Type
Placebo Comparator
Arm Description
Phase 1: Participants will wear an accelerometer device daily but take no study drug for 14 days (washout period). On day 15, participants begin phase I study drug (Placebo) at 46 mg, at minimum of 4 hours apart, for 3 doses per day during the active portion of the participant's day. On day 22 participants increase study drug dose to 80 mg at the same frequency. Regardless of participant's ability to tolerate study drug or if the participant requires down-titration, participants will begin Phase 2. Phase 2: Is identical to Phase 1 except subject will be taking Nebulized Sodium Nitrite (AIR001) instead of Placebo.
Intervention Type
Drug
Intervention Name(s)
Nebulized Sodium Nitrite
Other Intervention Name(s)
AIR001
Intervention Description
Inhaled, nebulized inorganic sodium nitrite vs. inhaled, nebulized placebo at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Inhaled, nebulized placebo vs. inhaled, nebulized inorganic sodium nitrite at a dose of 80 mg (or maximally tolerated dose) administered at a minimum of 4 hours apart, three times per day, during the active part of the day.
Primary Outcome Measure Information:
Title
Peak VO2
Description
The primary endpoint will be the peak VO2 after 4 weeks treatment with inorganic nitrite as compared to the peak VO2 after 4 weeks treatment with placebo as assessed by cardiopulmonary exercise testing (CPET) performed at peak drug levels.
Time Frame
End of Phase 1 & End of Phase 2
Secondary Outcome Measure Information:
Title
Average Arbitrary Accelerometer Units (AAU)
Description
Average arbitrary accelerometer units (AAU) during at least 14 days and up to 21 days of the maximally tolerated dose of study drug (from 28 days post Study Visit 1 until Study Visit 2 and from 28 days post Study Visit 2 until Study Visit 3). An arbitrary accelerometer unit is calculated within the accelerometer device that is worn by the patient and represents level of activity based upon patient movement. Higher values indicate more movement. Zero indicates no movement.
Time Frame
End of Phase 1 & End of Phase 2
Title
Medial E/e' Ratio as Measured by Echocardiography Core Lab
Description
To evaluate whether AIR001 improves Medial E/e' ratio (the ratio between early mitral inflow velocity and mitral annular early diastolic velocity for diastolic evaluation) in comparison to placebo.
Time Frame
End of Phase 1 & End of Phase 2
Title
Left Atrial Volume Index as Measured by Echocardiography
Description
To evaluate whether AIR001 improves Left atrial volume index in comparison to placebo.
Time Frame
End of Phase 1 & End of Phase 2
Title
Pulmonary Artery Systolic Pressure as Measured by Echocardiography
Description
To evaluate whether AIR001 improves pulmonary artery systolic pressure in comparison to placebo.
Time Frame
End of Phase 1 & End of Phase 2
Title
Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Score
Description
To evaluate whether AR001 improves quality of life in comparison to placebo. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcomes measure for patients with heart failure. It consists of 23 items, is comprised of 7 clinically relevant scales (Symptom Frequency, Symptom Burden, Symptom Stability, Physical Limitation, Social Limitation, Quality of Life, and Self-Efficacy), and yields 3 summary scores (Clinical Summary, Total Symptom, and Overall Summary Scores). Scale and summary scores range between 0 and 100, with higher scores indicating better health status (eg, better functioning, fewer symptoms, better quality of life). Higher values of the overall KCCQ score are considered to be better than lower values.
Time Frame
End of Phase 1 & End of Phase 2
Title
N-terminal Pro-B-type Natriuretic Peptide Level (NT-proBNP)
Description
Evaluate whether AIR001 improves natriuretic peptide levels in comparison to placebo
Time Frame
End of Phase 1 & End of Phase 2
Title
NYHA (New York Heart Association) Class
Description
To evaluate whether AR001 improves NYHA Class in comparison to placebo. NYHA class was measured at the end of each phase. The site physician evaluated the patient based upon the criteria for NYHA class I-IV used by the American Heart Association. NYHA functional classification provides a way of classifying the extent of heart failure. Class I (least severe): No limitation of physical activity; Class II: Slight limitation of physical activity; Class III: Marked limitation of physical activity; Class IV (most severe): Unable to carry on any physical activity without discomfort.
Time Frame
End of Phase 1 & End of Phase 2
Title
Patient Preference for AIR001 Treatment at the End of Study
Description
Self-reported participant preference for study period 1 (Phase 1) vs. study period 2 (Phase 2)
Time Frame
End of Phase 2
Title
VE/VCO2 Slope (Ventilatory Efficiency) as Provided by Cardiopulmonary Exercise Testing Core Lab
Description
To evaluate whether ARI001 in comparison to placebo improves ventilator efficiency as measured by Slope of Ve/VCO2 during study drug administration. The Ve/VCO2 slope is defined as the slope of the linear relationship between ventilation and carbon dioxide output and is a measure of the velocity.
Time Frame
End of Phase 1 & End of Phase 2
Title
VO2 at Ventilatory Threshold (Submaximal Exercise Capacity) as Provided by Cardiopulmonary Exercise Testing Core Lab
Description
To evaluate whether ARI001 in comparison to placebo improves submaximal exercise capacity as measured by VO2 (rate of oxygen consumption measured during incremental exercise) at ventilatory threshold during study drug administration.
Time Frame
End of Phase 1 & End of Phase 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 40 years Symptoms of dyspnea (NYHA class II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea EF ≥ 50% as determined on imaging study within 12 months of enrollment with no change in clinical status suggesting potential for deterioration in systolic function One of the following : Previous hospitalization for HF with radiographic evidence (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) of pulmonary congestion or Catheterization documented elevated filling pressures at rest (PCWP ≥15 or LVEDP ≥18) or with exercise (PCWP ≥25) or Elevated NT-proBNP (>400 pg/ml) or BNP(>200 pg/ml) or Echo evidence of diastolic dysfunction/elevated filling pressures manifest by medial E/e' ratio≥15 and/or left atrial enlargement and chronic treatment with a loop diuretic for signs or symptoms of heart failure Heart failure is primary factor limiting activity as indicated by answering # 2 to the following question: My ability to be active is most limited by: Joint, foot, leg, hip or back pain Shortness of breath and/or fatigue and/or chest pain Unsteadiness or dizziness Lifestyle, weather, or I just don't like to be active 6. Peak VO2 ≤75% predicted with peak respiratory exchange ratio≥1.0 CPET Normal Values for Peak VO2* Criteria (ml/kg/min) 7. No chronic nitrate therapy or not using intermittent sublingual nitroglycerin (requirement for >1 SL nitroglycerin per week) within last 7 days 8. No daily use of phosphodiesterase 5 inhibitors or soluble guanylyl cyclase activators and willing to withhold prn use of phosphodiesterase 5 inhibitors for duration of study 9. Ambulatory (not wheelchair / scooter dependent) 10. Body size allows wearing of the accelerometer belt as confirmed by ability to comfortably fasten the test belt provided for the screening process (belt designed to fit persons with BMI 20-40 kg/m2 but belt may fit some persons outside this range) 11. Willingness to wear the accelerometer belt for the duration of the trial 12. Willingness to provide informed consent Exclusion Criteria: Recent (< 1 month) hospitalization for heart failure Ongoing requirement for PDE5 inhibitor, organic nitrate or soluble guanylyl cyclase activators Hemoglobin (Hgb) < 8.0 g/dl within 90 days prior to randomization GFR < 20 ml/min/1.73 m2 within 90 days prior to randomization Systolic blood pressure < 115 mmHg seated or < 90 mmHg standing just prior to test dose Resting HR > 110 just prior to test dose Previous adverse reaction to the study drug which necessitated withdrawal of therapy Significant chronic obstructive pulmonary disease thought to contribute to dyspnea Ischemia thought to contribute to dyspnea Documentation of previous EF < 45% Acute coronary syndrome within 3 months defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g., troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent) PCI, coronary artery bypass grafting, or new biventricular pacing within past 3 months Primary hypertrophic cardiomyopathy Infiltrative cardiomyopathy (amyloid) Constrictive pericarditis or tamponade Active myocarditis Complex congenital heart disease Active collagen vascular disease More than mild aortic or mitral stenosis Intrinsic (prolapse, rheumatic) valve disease with moderate to severe or severe mitral, tricuspid or aortic regurgitation Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, INR > 1.7 in the absence of anticoagulation treatment Terminal illness (other than HF) with expected survival of less than 1 year Regularly (> 1x per week) swims or does water aerobics Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months. Inability to comply with planned study procedures Pregnancy or breastfeeding mothers
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kevin Hernandez, MD
Organizational Affiliation
Duke Clinical Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eugene Braunwald, MD
Organizational Affiliation
Harvard University
Official's Role
Study Chair
Facility Information:
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston V.A. Healthcare System
City
West Roxbury
State/Province
Massachusetts
ZIP/Postal Code
02132
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Missouri Health System
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
V.A St. Louis Health Care System
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63106
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Stony Brook University Medical Center
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Metro Health System
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Abington Memorial Hospital
City
Abington
State/Province
Pennsylvania
ZIP/Postal Code
19001
Country
United States
Facility Name
University of Pennsylvania Health System
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Jefferson Medical College
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
The University of Vermont - Fletcher Allen Health Care
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
After study completion, and upon site request, site specific participant data will be shared upon site requests. Sites may share this data with participants according to their individual institution's Institutional Review Board (IRB) policy.
Citations:
PubMed Identifier
32150314
Citation
Reddy YNV, Rikhi A, Obokata M, Shah SJ, Lewis GD, AbouEzzedine OF, Dunlay S, McNulty S, Chakraborty H, Stevenson LW, Redfield MM, Borlaug BA. Quality of life in heart failure with preserved ejection fraction: importance of obesity, functional capacity, and physical inactivity. Eur J Heart Fail. 2020 Jun;22(6):1009-1018. doi: 10.1002/ejhf.1788. Epub 2020 Mar 9.
Results Reference
derived
PubMed Identifier
30398602
Citation
Borlaug BA, Anstrom KJ, Lewis GD, Shah SJ, Levine JA, Koepp GA, Givertz MM, Felker GM, LeWinter MM, Mann DL, Margulies KB, Smith AL, Tang WHW, Whellan DJ, Chen HH, Davila-Roman VG, McNulty S, Desvigne-Nickens P, Hernandez AF, Braunwald E, Redfield MM; National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network. Effect of Inorganic Nitrite vs Placebo on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction: The INDIE-HFpEF Randomized Clinical Trial. JAMA. 2018 Nov 6;320(17):1764-1773. doi: 10.1001/jama.2018.14852.
Results Reference
derived
PubMed Identifier
28476756
Citation
Reddy YNV, Lewis GD, Shah SJ, LeWinter M, Semigran M, Davila-Roman VG, Anstrom K, Hernandez A, Braunwald E, Redfield MM, Borlaug BA. INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction): Rationale and Design. Circ Heart Fail. 2017 May;10(5):e003862. doi: 10.1161/CIRCHEARTFAILURE.117.003862.
Results Reference
derived

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Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF

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