Phase 3
N=2,743
A Comparison Of Outcomes In Patients In New York Heart Association (NYHA) Class II Heart Failure When Treated With Eplerenone Or Placebo In Addition To Standard Heart Failure Medicines
Heart Failure
Bottom Line
View on ClinicalTrials.gov: NCT00232180 ↗Enrolled (actual)
2,743
Serious AEs
39.4%
Results posted
Jun 2011
Primary outcome: Primary: Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated): Up to Cut-off Date — 249; 356 participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Eplerenone (Drug)
- Age
- Adult, Older Adult · 55+ yrs
- Sex
- All
- Sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Primary completion
- May 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated): Up to Cut-off Date |
249; 356 | <0.0001 sig |
| PRIMARY Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated) |
288; 392 | — |
| SECONDARY Number of Participants With First Occurrence of All-Cause Mortality or Heart Failure (HF) Hospitalization (Adjudicated) |
270; 376; 311; 418 | <0.0001 sig |
| SECONDARY Number of Participants With First Occurrence of All-Cause Mortality (Adjudicated) |
171; 213; 205; 253 | 0.0081 sig |
| SECONDARY Number of Participants With First Occurrence of Cardiovascular (CV) Mortality (Adjudicated) |
147; 185; 178; 215 | 0.0120 sig |
| SECONDARY Number of Participants With First Occurrence of All-Cause Hospitalization (Adjudicated) |
408; 491; 463; 552 | <0.0001 sig |
| SECONDARY Number of Participants With First Occurrence of Heart Failure (HF) Hospitalization (Adjudicated) |
164; 253; 186; 277 | <0.0001 sig |
| SECONDARY Number of Participants With First Occurrence of All-Cause Mortality or All-Cause Hospitalization (Adjudicated) |
462; 569; 530; 636 | <0.0001 sig |
| SECONDARY Number of Participants With First Occurrence Of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization (Adjudicated) |
170; 262; 194; 287 | <0.0001 sig |
| SECONDARY Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization (Adjudicated) |
304; 399; 346; 439 | <0.0001 sig |
| SECONDARY Number of Participants With First Occurrence of Fatal or Non-fatal Myocardial Infarction (Adjudicated) |
45; 33; 49; 40 | 0.2321 |
| SECONDARY Number of Participants With First Occurrence of Fatal or Non-fatal Stroke (Adjudicated) |
21; 26; 24; 31 | 0.4213 |
| SECONDARY Number of Participants With First Occurrence of Implantation of Cardiac Defibrillator (ICD) (Adjudicated) |
61; 59; 76; 78 | 0.9754 |
| SECONDARY Number of Participants With First Occurrence of Implantation of Resynchronization Device (Cardiac Resynchronization Therapy [CRT]) (Adjudicated) |
33; 41; 45; 53 | 0.2652 |
| SECONDARY Number of Participants With First Occurrence of Hospitalization Due to Worsening Renal Function (Adjudicated) |
9; 8; 10; 10 | 0.9537 |
| SECONDARY Number of Participants With First Occurrence of Hospitalization Due to Hyperkalemia (Adjudicated) |
4; 3; 4; 3 | 0.8539 |
| SECONDARY Number of Participants With New Onset Atrial Fibrillation or Flutter |
32; 52; 41; 59 | 0.0175 sig |
| SECONDARY Number of Participants With New Onset Diabetes Mellitus (DM) |
34; 40; 42; 47 | 0.6009 |
Summary
In an earlier study, eplerenone was shown to improve survival in patients who had heart failure immediately following a heart attack. However, it is not known how patients with established mild-to-moderate heart failure (NYHA Class II), who have the additional risk of sudden death, will respond if treated with eplerenone. In this trial, eplerenone plus standard heart failure medicines is being compared to placebo plus standard heart failure medicines in terms of an additional ability to prolong life and prevent re-hospitalizations for worsening heart failure in these patients.
The Data Safety Monitoring Committee (DSMC) observed during its conduct of the protocol-specified second interim analysis on the 6th of May, 2010 that the efficacy of eplerenone had met the pre-specified stopping rules in the protocol. As a result of the discussion between the DSMC and the Executive Steering Committee (ESC), the ESC recommended that EMPHASIS-HF should be terminated, Based on the convincing efficacy and the consideration that it would be unethical not to offer this treatment to patients, the ESC recommended that all the patients in the trial should be transferred to open-label eplerenone. The Open Label Extension eplerenone arm will last for 12 months. Eplerenone is not currently approved for the indication studied in this patient population.
On May 26, 2010, further enrollment into EMPHASIS-HF was stopped. The amendment is considered to be the most appropriate way to ensure that all the subjects who participated in the double-blind phase of the EMPHASIS-HF trial can be offered treatment with eplerenone
Eligibility Criteria
Inclusion Criteria
- History (Hx) of chronic systolic heart failure of ischemic or non-ischemic etiology of at least 4 weeks duration; Currently, New York Heart Association (NYHA) functional Class II and on optimal dose, or maximally tolerated dose of standard heart failure medicines (advisable to include ACE-I/ARBs; beta-blockers) and diuretics if indicated for fluid overload. Should have participated in the double-blind phase of the EMPHASIS-HF trial
Exclusion Criteria
- Severe chronic systolic heart failure symptomatic at rest despite optimal medical therapy; estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2.
Data sourced from ClinicalTrials.gov (NCT00232180). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.