Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT)
Condition: Acute Heart Failure
MeSH terms: Heart Failure
Intervention: Liraglutide; Placebo
Intervention description: Active Drug; Placebo
Intervention MeSH terms: Liraglutide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 300.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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