Survival and Prognosis: Investigation of Crataegus Extract WS 1442 in congestive heart failure ( SPICE) - rationale, study design and study protocol

SPICE is the first, international, randomized, placebo-controlled, double-b lind study to investigate the influence of the herbal drug Crataegus Specia l Extract WS 1442 (hawthorn leaves with flowers) on mortality of patients s uffering from congestive heart failure. Background: In vitro and experiment al animal studies have suggested the following pharmacological modes of act ion of standardized Crataegus extracts: (1) cAMP-independent positive inotr opy; (2) peripheral and coronary vasodilation; (3) protection against ische mia-induced ventricular arrhythmias; (4) antioxidative properties; and (5) antiinflammatory effects. Study design: In this randomized, placebo-control led, double-blind, international trial (approximately 120 investigational c enters in seven European countries), up to 2300 patients with congestive he art failure, New York Heart Association class II and III and markedly impai red left ventricular function, will be enrolled and treated over a period o f 24 months. During this time patients receive either two film-coated table ts of 450 mg of the Special Extract WS 1442 standardized to 84.3 mg of olig omeric procyanidines or matched placebo per day in addition to standard the rapy for congestive heart failure, such as diuretics, digoxin or digitoxin, beta -adrenoceptor blockers and angiotensin-converting-enzyme inhibitors. The primary outcome variable is the combined endpoint of cardiac death, non -lethal myocardial infarction, and hospitalization due to progression of he art failure. Secondary outcome variables are total mortality, exercise dura tion, echocardiographic parameters, quality of life as well as pharmacoecon omic parameters. The first patient was included in October 1998. The trial is expected to be completed at the end of 2002. (C) European Society of Car diology. All rights reserved.