Growth Hormone in Ischemic Heart Failure

Overview

In a double-blind, placebo-controlled trial, we randomly assigned 37 patients (mean age 66 years; 95% male) with ischemic heart failure (HF) (ejection fraction (EF) \< 40%) to a 9-month treatment with either recombinant human GH (1.4 mg every other day) or placebo, with subsequent 3-month treatment-free follow-up. The primary outcome was change in left ventricular (LV) end-systolic volume measured by cardiac magnetic resonance (CMR). Secondary outcomes comprised changes in cardiac structure and EF. Prespecified tertiary outcomes included changes in New York Heat Association (NYHA) functional class and quality of life (QoL), as well as levels of insulin-like growth factor-1 (IGF-1) and N-terminal pro-brain natriuretic peptide (NT-proBNP).

TITLE: GROWTH HORMONE IN HEART FAILURE Addition of recombinant human growth hormone to standard heart failure therapy in patients with congestive heart failure due to ischaemic heart disease. A 12 month study, consisting of a 9 month double-blind, placebo-controlled randomised growth hormone treatment phase followed by a 3 month growth hormone treatment-free period. STUDY PHASE: III COORDINATING CENTRE: Endocrine Cardiac Unit (ECU) Sahlgrenska University Hospital, Sahlgrenska S-413 45 Göteborg Sweden STUDY PRODUCT: Somatropin, recombinant human growth hormone (rhGH), Saizen® 8 mg (24 IE). CONTROL PRODUCT: Placebo for Saizen® DOSAGE OF STUDY PRODUCT: 1,4 mg (4,2 IE) every other day. DOSAGE: 9 month treatment period and a 3 month follow-up period. ROUTE OF ADMINISTRATION One subcutaneous injection of Saizen® of study product, or corresponding placebo in the thigh or abdomen given in the evening given every other day. STUDY DESIGN: Double-blind (regarding treatment), parallel, placebo-controlled, randomised. STUDY POPULATION: Female and male patients 75 years of age or below with congestive heart failure (NYHA class II or III) due to ischemic heart disease. NUMBER OF PATIENTs: 54 evaluable patients. MULTICENTRE: Yes. NUMBER OF CENTRES: Four ALLOCATION OF TREATMENT: Randomisation to treatment if all inclusion/exclusion criteria are met. PRIMARY OBJECTIVE: To investigate the effect of subcutaneously administered Saizen® compared with placebo on left ventricular endsystolic volume by MRI in patients with congestive heart failure due to ischaemic heart disease. SECONDARY OBJECTIVE: To determine the effect of Saizen® on enddiastolic volume, left ventricular mass and left ventricular ejection fraction TERTIARY OBJECTIVES: To determine the effect of Saizen® on change in NYHA class after 9 months of follow up. To determine the effect of Saizen® on circulating levels of IGF-I and IGFBP-3 and to evaluate the correlation between changes in IGF-I and the respective changes in left ventricular ejection fraction, wall stress and left ventricular mass. To evaluate the effect of Saizen® on quality of life by using two different questionnaires (Minnesota - Living with Heart Failure and Cardiac Health Profile). To determine the effect of Saizen® on neurohormonal activation by measuring NT-proBNP SAFETY VARIABLES: Hospitalization, morbidity and mortality. * Clinical events, including tendency to fluid retention, glucose intolerance, arrhythmias and worsening heart failure. * Electrolytes, haematology, prothrombin complex, parameters for renal and hepatic function. ADVERSE EVENTS: Spontaneously reported from patients and asked for. To be recorded in Case Report Forms (CRFs) and on separate Adverse Event form if serious Adverse Event. STATISTICS AND DATABASE MANAGEMENT: Data management will be performed by Scandinavian Contract Research Institute and when clean file is declared data will be made available to the statistician for the analysis. The analysis will be performed according to the intention to treat principle.