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Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Duke University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01800968
First received: February 7, 2013
Last updated: October 7, 2014
Last verified: October 2014
  Purpose

The primary objective is to test the hypothesis that, compared with placebo, therapy with Subcutaneous (SQ) GLP-1 agonist in the post-Acute Heart Failure Syndrome (AHFS) discharge period will be associated with greater clinical stability at six months as assessed by a composite clinical endpoint.


Condition Intervention Phase
Acute Heart Failure
Drug: Liraglutide
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Functional Impact of GLP-1 for Heart Failure Treatment

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Global Ranking of predefined events [ Time Frame: Randomization to 180 days ] [ Designated as safety issue: Yes ]

    All patients participating(regardless of treatment assignment) will be ranked on the basis of a prespecified hierarchical ranking of the following:

    1. Time to death
    2. Time to HF hospitalization
    3. Time-averaged proportional change in Pro-B-type Natriuretic peptide (NT-proBNP) (baseline to 180 days)


Secondary Outcome Measures:
  • Change in Cardiac Structure and function [ Time Frame: Baseline to 180 days ] [ Designated as safety issue: No ]
    Change in cardiac structure and function (by echocardiography) from baseline to 180 days.

  • Individual Component of the primary endpoint- Time to death [ Time Frame: Randomization to 30, 90 and 180 days ] [ Designated as safety issue: No ]
    Individual component of the primary endpoint of Death at 30, 90 and 180 days after randomization

  • Number of combined events- Death, HF hospitalization and ED visits [ Time Frame: Randomization to day 210 ] [ Designated as safety issue: Yes ]

    Number of combined events:

    1. Death and HF hospitalization or
    2. Death + HF hospitalization + Emergency Department (ED) visits

  • Change in symptoms using the Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: Baseline to day 180 ] [ Designated as safety issue: No ]
    Change in KQQC symptoms.

  • Functional Status (6MWT) [ Time Frame: Baseline, 30, 90 and 180 days ] [ Designated as safety issue: No ]
    Functional status change at 30, 90 and 180 days.

  • Individual component of the primary endpoint- time to HF hospitalization [ Time Frame: Randomization to 30, 60 and 180 days ] [ Designated as safety issue: No ]
    Individual component of the primary endpoint- time to HF hospitalization from randomization to 30, 60 and 90 days

  • Individual component of the primary endpoint- time-averaged proportional change in NT-proBNP [ Time Frame: Baseline to 180 days ] [ Designated as safety issue: No ]
    Individual component of the primary endpoint- time-averaged proportional change in NT-proBNP from baseline to 180 days


Estimated Enrollment: 300
Study Start Date: April 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Liraglutide
Increasing dose from 0.6mg, 1.2mg to 1.8mg SQ daily.
Drug: Liraglutide
Active Drug
Other Name: Victoza
Placebo Comparator: Placebo
Placebo dose increasing from 0.6mg, 1.2mg to 1.8 mg SQ daily.
Drug: Placebo
Placebo
Other Name: Placebo

Detailed Description:

Hospitalization for AHFS identifies individuals at increased risk of death and re-hospitalization following discharge. This increased risk justifies intervention with novel therapy during the vulnerable post-discharge period to enhance clinical stability and prevent early HF mortality and readmissions.

As heart failure (HF) progresses, impairments in metabolism render the heart substrate constrained, limiting cardiac metabolism. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin peptide that enhances cellular glucose uptake by stimulating insulin secretion and insulin sensitivity in target tissues. Preclinical and early-phase clinical data support GLP-1 as an effective therapy for advanced HF while use of GLP-1 receptor agonists in large numbers of patients with diabetes reveal a good safety profile and reductions in adverse cardiac outcomes.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. AHFS as defined by the presence of at least 1 symptom (dyspnea, orthopnea, or edema) AND 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography)
  3. AHFS is the primary cause of hospitalization
  4. Prior clinical diagnosis of HF
  5. Left Ventricular Ejection Fraction(LVEF) ≤ 40% during the preceding 3 months (if no echo within the preceding 3 months, an LVEF ≤ 30% during the preceding three years is acceptable)
  6. On evidence-based medication for HF (including beta-blocker and ACE-inhibitor/ARB) or previously deemed intolerant
  7. Use of at least 80 mg or furosemide total daily dose (or equivalent) prior to admission for AHFS (a lower dose of a loop diuretic combined with a thiazide will count as an "equivalent")
  8. Willingness to provide informed consent

Exclusion Criteria:

  1. AHFS due to acute myocarditis or acute Myocardial Infarction
  2. Ongoing hemodynamically significant arrhythmias contributing to HF decompensation
  3. Inotrope, intra-aortic balloon pump (IABP) or other mechanical circulatory support use at the time of consent. Prior use will not exclude a patient.
  4. Current or planned left ventricular assist device therapy in next 180 days
  5. United Network for Organ Sharing status 1A or 1B
  6. B-type natriuretic peptide(BNP)< 250 or NT-proBNP<1,000 (Not required per protocol but if available and too low would be an exclusion; within 48 hours of consent)
  7. Hemoglobin (Hgb) < 8.0 g/dl
  8. Glomerular filtration rate(GFR) < 20 ml/min/1.73 m2 within 48 hours of consent
  9. Systolic blood pressure < 80 mmHg at consent
  10. Resting Heart Rate > 110 at consent
  11. Acute coronary syndrome within 4 weeks as defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g. troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)
  12. Percutaneous Coronary Intervention, coronary artery bypass grafting or new biventricular pacing within past 4 weeks
  13. Primary hypertrophic cardiomyopathy
  14. Infiltrative cardiomyopathy
  15. Constrictive pericarditis or tamponade
  16. Complex congenital heart disease
  17. Non-cardiac pulmonary edema
  18. More than moderate aortic or mitral stenosis
  19. Intrinsic (prolapse, rheumatic) valve disease with severe mitral, aortic or tricuspid regurgitation
  20. Sepsis, active infection (excluding cystitis) or other comorbidity driving the HF decompensation
  21. Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, International Normalized Ration (INR) > 1.7 in the absence of anticoagulation treatment
  22. Terminal illness (other than HF) with expected survival of less than 1 year
  23. Previous adverse reaction to the study drug
  24. Receipt of any investigational product in the previous 30 days.
  25. Enrollment or planned enrollment in another randomized therapeutic clinical trial in next 6 months.
  26. Inability to comply with planned study procedures
  27. Pregnancy or breastfeeding mothers
  28. Women of reproductive age not on adequate contraception
  29. History of acute or chronic pancreatitis
  30. History of symptomatic gastroparesis
  31. Familial or personal history of medullary thyroid cancer or multiple endocrine neoplasia type-2 (MEN2)
  32. Prior weight-loss surgery (i.e., Roux-en-Y gastric bypass) or other gastric surgery associated with increased endogenous GLP-1 production
  33. Prior or ongoing treatment with GLP-1 receptor agonists
  34. Ongoing treatment with dipeptidyl peptide-IV inhibitors (1 week washout required)
  35. Ongoing treatment with thiazolidinedione
  36. Oxygen-dependent chronic obstructive pulmonary disease
  37. Diabetic patients with history of 2 or more severe hypoglycemia, Diabetic Ketoacidosis(DKA) or hyperglycemic, hyperosmotic nonketotic coma in the preceding 12 months.
  38. Diagnosis of Type 1 Diabetes Mellitus

40. If diabetic, inadequate glycemic control with glucose level > 300 mg/dL within 24 hours of randomization

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01800968

Contacts
Contact: Doris Coleman 919-668-8042 doris.coleman@duke.edu

  Show 25 Study Locations
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Adrian Hernandez, MD Duke University
Study Chair: Eugene Bruanwald, MD Harvard University
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01800968     History of Changes
Other Study ID Numbers: Pro00042633
Study First Received: February 7, 2013
Last Updated: October 7, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Liraglutide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 19, 2014