FIGHT-HF

Overview

Status: Recruiting
Keywords: Heart Failure , Heart , Liraglutide , Victoza
IRB Number: 00062974
Specialty: Cardiology, Cardiology, Cardiology
Sub Specialties: General Cardiology, Heart Failure

Brief Summary

Primary Hypothesis
The over-arching hypothesis of the FIGHT study is that, compared with placebo, therapy with subcutaneous (SQ) glucagon-like peptide-1 (GLP-1) agonist in the post-acute heart failure syndrome (AHFS) discharge period will be associated with greater clinical stability through 180 days as assessed by a composite clinical endpoint.

This hypothesis will be tested based on a novel global rank endpoint in which all participants are ranked across three hierarchical groups: 1) time to death, 2) time to heart failure (HF) hospitalization and 3) time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) (from baseline to 180 days).

The broad objective is to provide the rationale for a larger randomized clinical trial testing the effect of GLP-1 agonist therapy on clinical endpoints.

Secondary Objectives
Secondary objectives will be to examine the effect of treatment on:
1. Change in cardiac structure and function (by echocardiography) from baseline to 180 days.
2. Functional status: 6-minute walk test (6MWT) at 30, 90 and 180 days
3. Change in symptoms (using the Kansas City Cardiomyopathy Questionnaire [KCCQ]) from baseline to 180 days
4. Individual components of the primary endpoint at 30, 90 and 180 days after randomization
5. Number of combined events (death + HF hospitalization or death + HF hospitalization + ED visits)
2.3 Tertiary Objectives

Tertiary objectives of the study will be to examine the effects of study treatments on:
1. Change in AHFS biomarker panel (including ST2, cystatin C, hsCRP) from baseline to 30, 90 and 180 days.
2. Change in glycosylated hemoglobin at 30, 90 and 180 days after randomization.
3. Change in weight.
4. Change in insulin resistance (as assessed by HOMA-IR in both diabetic and non-diabetic patients).
5. Change in fasting lipids

Principal Investigator: Josef Stehlik
Department: Cardiology
Co Investigator: Stavros Drakos
Co Investigator: Jose Nativi-Nicolau
Co Investigator: Edward Gilbert

Contact Information

Name:Melissa Whipple
Phone: 801-587-9048
Email: melissa.whipple@hsc.utah.edu

Inclusion 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 (can be randomized within 14 days post qualifying AHFS admission)
4. Prior clinical diagnosis of HF
5. 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 40 mg of 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

Exclusion Criteria
1. AHFS due to acute myocarditis or acute MI
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. 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. GFR < 20 ml/min/1.73 m2 within 48 hours of consent
9. Systolic blood pressure < 80 mmHg at consent
10. Resting HR > 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. PCI, 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, 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. Ongoing treatment with GLP-1 receptor agonists
34. Ongoing treatment with dipeptidyl peptide-IV inhibitors (1 week washout required)
35. Ongoing treatment with thiazolidinedione therapy
36. Oxygen-dependent chronic obstructive pulmonary disease
37. Diabetic patients with history of 2 or more severe hypoglycemia episodes, DKA or hyperglycemic, hyperosmotic nonketotic coma in the preceding 12 months.
38. Diagnosis of Type 1 Diabetes Mellitus
39. If diabetic, inadequate glycemic control with glucose level > 300 mg/dL within 24 hours of randomization