Functional Impact of GLP-1 for Heart Failure Treatment

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

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.

Who is eligible to participate?

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

Last updated:

10/7/2014

NCT ID:

NCT01800968

IRB Number:

12-009924