Pfizer Inc plans to halt recruitment to the EMPHASIS-HF trial early on the recommendations of the trial’s independent Executive Steering Committee (ESC). The recommendations follow a second interim analysis by the independent Data Safety Monitoring Committee (DSMC) of the EMPHASIS-HF trial confirming the study has reached its primary efficacy endpoint early according to the protocol pre-defined stopping rules.
The interim analysis showed that patients treated with Inspra (eplerenone), in addition to current standard of care, experienced a significant reduction in risk of cardiovascular (CV) death or heart failure (HF) hospitalization compared with those on the placebo arm of the trial where patients received
standard of care in addition to a matching placebo. Based upon the interim analyses by the independent data safety monitoring committee, eplerenone, generally, was well tolerated during the EMPHASIS-HF trial. Adverse events reported included hyperkalemia (elevated potassium) (8 per cent of the eplerenone
group vs 3% in the placebo group; p < 0.001) and renal impairment (4 per cent in the eplerenone group vs 2% in the placebo group; p < 0.05). These adverse events are common with mineralcorticoid
receptor antagonist agents.
The EMPHASIS-HF trial was a double-blind, placebo-controlled, parallel group trial comparing the effect of eplerenone plus standard heart failure therapy versus placebo plus standard heart failure therapy on mortality and morbidity outcomes in patients with mild chronic systolic heart failure (NYHA functional Class II) and left ventricular systolic dysfunction. The composite primary endpoints were the first occurrence of either cardiovascular (CV) death or heart failure (HF) hospitalization.
The EMPHASIS-HF trial was to enrol approximately 3,100 patients and was to continue until a total of 813 adjudicated primary endpoint events were reported. Inspra does not have a licence for use in the patient population studied in the EMPAHSIS-HF trial in any individual market.
Professor Faiez Zannad, Inserm and University of Nancy, France, co-chair of the Executive Steering Committee, commented, “It is not common for clinical studies to conclude early for reasons of efficacy. The EMPHASIS-HF trial had an estimated end date around October 2011 so to have met the pre-defined efficacy endpoints early is certainly a positive outcome.”
Pfizer has informed the relevant Regulatory Agencies, Ethics Committees/Independent Review Boards and Investigators as appropriate in countries where the trial was being conducted, and continues to work with the DSMC, Executive Steering Committee and all study investigators globally. In addition, Pfizer is working to ensure all patients are informed via their clinicians and an amendment to the protocol will be requested in order to allow all consenting patients to start treatment with eplerenone in an open label extension of the study, after completing a close-out visit ending the double-blind placebo-controlled phase.
Inspra (eplerenone) is a steroid nucleus-based mineralcorticoid receptor (MR) antagonist with a higher degree of selectivity than spironolactone. Eplerenone acts as a competitive and selective aldosterone blocker (SAB) at the mineralocorticoid receptor sites in various tissues throughout the body.