NCT02053493

Brief Summary

A randomized, double-blinded, placebo-controlled crossover study to assess effect of isosorbide mononitrate with dose up-titration on activity tolerance as assessed by (hip-worn, tri-axial) accelerometry.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
110

participants targeted

Target at P50-P75 for phase_2 heart-failure

Timeline
Completed

Started Apr 2014

Shorter than P25 for phase_2 heart-failure

Geographic Reach
1 country

22 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 3, 2014

Completed
1 month until next milestone

First Posted

Study publicly available on registry

February 3, 2014

Completed
2 months until next milestone

Study Start

First participant enrolled

April 1, 2014

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2015

Completed
28 days until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
1.7 years until next milestone

Results Posted

Study results publicly available

November 28, 2016

Completed
Last Updated

November 28, 2016

Status Verified

October 1, 2016

Enrollment Period

10 months

First QC Date

January 3, 2014

Results QC Date

February 4, 2016

Last Update Submit

October 7, 2016

Conditions

Heart Failure

Keywords

Heart FailurePreserved Ejection Fraction

Outcome Measures

Primary Outcomes (2)

  • Arbitrary Accelerometry Units (AAU) (Phase I)

    To evaluate whether isosorbide mononitrate increases daily activity as assessed by 14-day averaged arbitrary accelerometry units in comparison to placebo. An arbitrary accelerometer unit is calculated within the accelerometer device that is worn by the patient and represents level of activity based on patient movement. Higher values indicate more movement. 0 indicates no movement.

    5-6 weeks

  • Arbitrary Accelerometry Units (AAU) (Phase II)

    To evaluate whether isosorbide mononitrate increases daily activity as assessed by 14-day averaged arbitrary accelerometry units in comparison to placebo. An arbitrary accelerometer unit is calculated within the accelerometer device that is worn by the patient and represents level of activity based on patient movement. Higher values indicate more movement. 0 indicates no movement.

    11-12 weeks

Secondary Outcomes (15)

  • Six Minute Walk Distance (Phase I)

    Week 7

  • Six Minute Walk Distance (Phase II)

    Week 13

  • Patient Preference for Isosorbide Mononitrate Treatment at the End of Study.

    Week 13

  • Borg Score During 6 Minute Walk Test (Phase I)

    Week 7

  • Borg Score During 6 Minute Walk Test (Phase II)

    Week 13

  • +10 more secondary outcomes

Study Arms (2)

Isosorbide Mononitrate

ACTIVE COMPARATOR

Isosorbide Mononitrate with dose up-titration (30 to 120 mg/day over 4 weeks)

Drug: Isosorbide Mononitrate

Isosorbide Mononitate Placebo

PLACEBO COMPARATOR

Isosorbide Mononitrate placebo with dose up-titration (30 to 120 mg/day over 4 weeks)

Drug: Placebo

Interventions

Isosorbide MononitrateDRUG

Dispense phase 1 study drug: Weeks 1 and 2: No study drug (baseline) Week 3: 30 mg ISMN Week 4: 60 mg ISMN Weeks 5 and 6: 120 mg ISMN Dispense phase-2 study drug: Weeks 7 and 8: No study drug (washout) Week 9: 30 mg ISMN Week 10: 60 mg ISMN Weeks 11 and 12: 120 mg ISMN

Also known as: Imdur, ISMO, Monoket
Isosorbide Mononitrate
PlaceboDRUG

Dispense phase 1 study drug: Weeks 1 and 2: No study drug (baseline) Week 3: 30 mg Placebo Week 4: 60 mg Placebo Weeks 5 and 6: 120 mg Placebo Dispense phase-2 study drug: Weeks 7 and 8: No study drug (washout) Week 9: 30 mg Placebo Week 10: 60 mg Placebo Weeks 11 and 12: 120 mg Placebo

Isosorbide Mononitate Placebo

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 50 years
  • Symptoms of dyspnea (NYHA class II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea
  • Ejection fraction (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
  • Stable medical therapy for 30 days as defined by:
  • No addition or removal of ACE, Angiotensin receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs) or aldosterone antagonists
  • No change in dosage of ACE, ARBs, beta-blockers,CCBs or aldosterone antagonists of more than 100%
  • One of the following within the last 12 months
  • Previous hospitalization for heart failure (HF) with radiographic evidence of pulmonary congestion (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) or
  • Catheterization documented elevated filling pressures at rest (LVEDP≥15 or PCWP≥20) 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 (at least two) E/A \> 1.5 + decrease in E/A of \> 0.5 with valsalva Deceleration time ≤ 140 ms Pulmonary vein velocity in systole \< diastole (PVs\<PVd)sinus rhythm) E/e'≥15 Left atrial enlargement (≥ moderate) Pulmonary artery systolic pressure \> 40 mmHg Evidence of left ventricular hypertrophy
  • LV mass/BSA ≥ 96 (♀) or ≥ 116 (♂) g/m2
  • Relative wall thickness ≥ 0.43 (♂ or ♀) \[(IVS+PW)/LVEDD\]
  • Posterior wall thickness ≥ 0.9 (♀) or 1.0 (♂) cm
  • No chronic nitrate therapy or infrequent (≤ 1x week) use of intermittent sublingual nitroglycerin within last 3 months
  • +9 more criteria

You may not qualify if:

  • Recent (\< 3 months) hospitalization for HF
  • Hemoglobin \< 8.0 g/dl
  • Glomerular filtration rate \< 20 ml/min/1.73 m2 on most recent clinical laboratories
  • SBP \< 110 mmHg or \> 180 mmHg at consent
  • Diastolic blood pressure \< 40 mmHg or \> 100 mmHg at consent
  • Resting HR \> 110 bpm at consent
  • Previous adverse reaction to nitrates necessitating withdrawal of therapy
  • Chronic therapy with phosphodiesterase type-5 inhibitors (intermittent use of phosphodiesterase type-5 inhibitors for erectile dysfunction is allowable if the patient is willing to hold for the duration of the trial)
  • Regularly (\> 1x per week) swims or does water aerobics
  • Significant COPD thought to contribute to dyspnea
  • Ischemia thought to contribute to dyspnea
  • Documentation of previous EF \< 50%
  • Acute coronary syndrome within 3 months defined by electrocardiographic changes and biomarkers of myocardial necrosis (e.g. troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)
  • Percutaneous coronary intervention, coronary artery bypass grafting or new biventricular pacing within past 3 months
  • Primary hypertrophic cardiomyopathy
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

Christiana Care Health Services

Newark, Delaware, 19718, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston V.A. Healthcare System

West Roxbury, Massachusetts, 02132, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Metro Health System

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17604, United States

Location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Jefferson Medical College

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Michael E Debakey VA Medical Center

Houston, Texas, 77030, United States

Location

University of Utah Hospitals and Clinics

Salt Lake City, Utah, 84132, United States

Location

V.A. Medical Center

Salt Lake City, Utah, 84148, United States

Location

The University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Related Publications (3)

  • 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.

    PMID: 32150314DERIVED

  • Snipelisky D, Kelly J, Levine JA, Koepp GA, Anstrom KJ, McNulty SE, Zakeri R, Felker GM, Hernandez AF, Braunwald E, Redfield MM. Accelerometer-Measured Daily Activity in Heart Failure With Preserved Ejection Fraction: Clinical Correlates and Association With Standard Heart Failure Severity Indices. Circ Heart Fail. 2017 Jun;10(6):e003878. doi: 10.1161/CIRCHEARTFAILURE.117.003878.

    PMID: 28588021DERIVED

  • Redfield MM, Anstrom KJ, Levine JA, Koepp GA, Borlaug BA, Chen HH, LeWinter MM, Joseph SM, Shah SJ, Semigran MJ, Felker GM, Cole RT, Reeves GR, Tedford RJ, Tang WH, McNulty SE, Velazquez EJ, Shah MR, Braunwald E; NHLBI Heart Failure Clinical Research Network. Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2015 Dec 10;373(24):2314-24. doi: 10.1056/NEJMoa1510774. Epub 2015 Nov 8.

    PMID: 26549714DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

isosorbide-5-mononitrate

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Results Point of Contact

Title
Dr. Adrian Hernandez
Organization
Duke Clinical Research Insitute
Adrian.Hernandez@duke.edu
919-668-7515

Study Officials

  • Kevin Anstrom, PhD

    Duke Clinical Research Institute

    PRINCIPAL INVESTIGATOR

  • Eugene Braunwald, MD

    Harvard University

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Medicine, DUMC; Director, Health Services and Outcomes Research, DCRI

Study Record Dates

First Submitted

January 3, 2014

First Posted

February 3, 2014

Study Start

April 1, 2014

Primary Completion

February 1, 2015

Study Completion

March 1, 2015

Last Updated

November 28, 2016

Results First Posted

November 28, 2016

Record last verified: 2016-10

Data Sharing

IPD Sharing
Will share

After the study results have been published, site-specific participant data will be shared with sites upon request. Sites are expected to follow their specific institutional policies regarding sharing results with their participants.

Locations

US(22)