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 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