Study design of a mortality trial with intravenous levosimendan (the SURVIVE study) in patients with acutely decompensated heart failure
© BioMed Central Ltd. 2004
Published: 15 March 2004
Acutely decompensated heart failure (ADHF) represents the most severe form of heart failure with a short-term mortality approaching 30%. The SURVIVE study is the first prospective, randomised trial utilising mortality as the primary variable in evaluating the efficacy of intravenous drug therapy in ADHF.
Levosimendan (LS) is a new calcium sensitiser for the treatment of ADHF. Previous studies with LS have shown decreased mortality in comparison with placebo or dobutamine (DB). The studies have, however, not been powered for mortality. A suspicion of detrimental mortality effect of DB has also been raised, but it has not been proven in any sufficiently powered single study or meta-analysis. Therefore, DB is still the most widely used intravenous (IV) inotropic agent in the treatment of ADHF.
The SURVIVE study is a multicentre, parallel-group, randomised, double-blind, double-dummy study in patients with ADHF comparing the efficacy of LS with that of DB.
The SURVIVE study includes hospitalised patients with ADHF, left ventricular ejection fraction ≤ 30% and clinical need for IV inotropic support. The primary endpoint of the study is all-cause mortality during 180 days following randomisation.
Patients will receive two simultaneous intravenous infusions, 'LS/placebo' with a maximum duration of 24 hours and 'DB/placebo' according to clinical judgement (but minimally for 24 hours and starting with a dose of 5 μg/kg/min). During the 180-day period, the originally randomised study drug can be re-administered when clinically justified.
Altogether 700 patients will be recruited. The sample size is based on assuming 30% 180-day mortality in the DB group, 33% relative risk reduction in the LS group, with a power of 85% and an alpha-level of 0.05.
The study is ongoing in eight countries (Finland, France, Germany, Israel, Latvia, Poland, Russia and UK).
After 450 patients have been followed for 1 month or after 90 deaths have occurred, the Data and Safety Monitoring Board will make a recommendation on the continuation/discontinuation of the study following pre-specified stopping rules. Separately, the Steering Committee follows the mortality rate without opening the treatment code and may recommend increasing the sample size.
SURVIVE thus represents the first study with two ambitious goals in ADHF: (1) to study a new drug against the accepted reference treatment, DB; (2) to assess mortality. In future, other trials will probably have to follow this new standard of design in this setting.