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

Abstract

SPICE is the first, international, randomized, placebo-controlled, double-blind study to investigate the influence of the Ž . herbal drug Crataegus Special Extract WS 1442 hawthorn leaves with flowers on mortality of patients suffering from congestive heart failure. Background: In vitro and experimental animal studies have suggested the following pharmacological Ž . Ž . modes of action of standardized Crataegus extracts: 1 cAMP-independent positive inotropy; 2 peripheral and coronary Ž . Ž . Ž . vasodilation; 3 protection against ischemia-induced ventricular arrhythmias; 4 antioxidative properties; and 5 anti-Ž inflammatory effects. Study design: In this randomized, placebo-controlled, double-blind, international trial approximately 120 . investigational centers in seven European countries , up to 2300 patients with congestive heart failure, New York Heart Association class II and III and markedly impaired left ventricular function, will be enrolled and treated over a period of 24 months. During this time patients receive either two film-coated tablets of 450 mg of the Special Extract WS 1442 standardized to 84.3 mg of oligomeric procyanidines or matched placebo per day in addition to standard therapy for congestive heart failure, such as diuretics, digoxin or digitoxin, ␤-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 heart failure. Secondary outcome variables are total mortality, exercise duration, echocardiographic parameters, quality of life as well as pharmacoeconomic parameters. The first patient was included in October

Development of an economic model to assess the cost-effectiveness of hawthorn extract as an adjunct treatment for heart failure in Australia

“…29 To date, there have only been two studies to examine the effect of hawthorn extract on heart failure progression in terms of mortality and hospitalisation. Most studies have focused on symptoms and exercise capability.…”

Vitamins, Supplements, Herbal Medicines, and Arrhythmias

“…Crataegus extract WS 1442 (2 450 mg per day) is being studied in a randomized, placebocontrolled, double-blind study (SPICE) of cardiac death, nonlethal myocardial infarction, and hospitalization resulting from progression of heart failure in patients with congestive heart failure. 96 Garlic has been reported to reduce ischemia and reperfusion-induced arrhythmias. These effects could, at least in part, be the result of antioxidant activity, because it has been reported to be a powerful scavenger of oxygen free radicals.…”

Naturoceutical Agents in the Management of Cardiovascular Disease

“…The ongoing Survival and Prognosis: Investigation of Crataegus Extract WS 1442 in congestive heart failure (SPICE) trial is a large, international, randomized, placebo-controlled, double-blind trial comparing the impact of a standardized extract of Hawthorn leaves and flowers with standard heart failure therapy (including β-adrenoceptor antagonists). [100] The primary variable is the combined endpoint of cardiac death, non-lethal MI and hospitalization for heart failure progression. Total mortality, exercise duration, ventricular function, quality of life and pharmacoeconomic measures are secondary outcome variables.…”

“…Total mortality, exercise duration, ventricular function, quality of life and pharmacoeconomic measures are secondary outcome variables. [100] Hawthorn is currently being evaluated in Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB-CHF) a US trial in patients with heart failure. [101] Although treatment with Hawthorn is generally considered to be well tolerated in Germany, there are several possible drug interactions to consider including potentiation of prescribed vasodilators and elevation of plasma digoxin concentrations via displacement of the plasma protein bound drug.…”