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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many clinical trials unintentionally include patients with a low risk of the trial endpoints. PRIME II (The Second Perspective Randomised study of Ibopamine on Mortality and Efficacy) was a large international randomised double blind trial comparing the addition of ibopamine or placebo to the therapy of patients with advanced heart failure. The trial was stopped prematurely because ibopamine was associated with an increased fatality rate, but the protocol achieved its objective of including high-risk patients. Here we describe the protocol details that enabled patients with the desired degree of risk to be included. We also amplify our definition of mode of death. The PRIME II protocol was designed with the intention that patients in the placebo group would have an annual fatality rate of 20%. Since the study was to be conducted in some 200 centres in 13 European countries, the inclusion criteria had to be simple and flexible, allowing for different clinical practice. The inclusion criteria, together with the use of simple investigations (which did not have to include angiographic or radionuclide ventriculography) are described. The annual fatality rate in the placebo group was just over 20%. Six categories of mode of death were used, but while they were reasonably easy to apply they did not reveal the reason for the unexpected adverse effect of ibopamine. The inclusion and exclusion criteria used for PRIME II, and the definitions of mode of death, were effective. The PRIME II protocol can be used as a model for future heart failure studies.
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PMID:Achieving appropriate endpoints in heart failure trials: the PRIME-II protocol. The Second Perspective Randomised study of Ibopamine on Mortality and Efficacy. 1093 85

In the periphery, physiological dopamine increases renal blood flow, decreases renal resistance and acts on the kidney tubule to enhance natriuresis and diuresis. The loss of dopamine function may be involoved in the deterioration in kidney function associated with ageing and may have a role in the pathogenesis of hypertension and diabetes. Intravenous dopamine is used as a positive inotrope in the treatment of acute heart failure and cardiogenic shock and as a diuretic in renal failure. The clinical uses of dopamine are limited, as it must be given intravenously, and also has widespread effects. The levels of peripheral dopamine can be increased by the administration of L-dopa to increase synthesis, prodrugs to release dopamine (docarpamine, glu-dopa) or by inhibiting the breakdown of dopamine (nitecapone). Preliminary clinical trials suggest that docarpamine may be useful in patients with low cardiac output syndrome after cardiac surgery and in refractory cirrhotic ascites. Ibopamine is an agonist at dopamine D1 and D2 receptors, which may retard the progression of chronic renal failure. Glu-dopa is selective for the kidney, thus avoiding widespread side effects. The early clinical studies with ibopamine as a diuretic in heart failure were favourable but the subsequent large mortality study showed that ibopamine increased mortality. Fenoldopam is a selective dopamine D1 receptor agonist. Intravenous fenoldopam may be useful in the treatment of hypertension associated with coronary artery bypass surgery or in hypertensive emergencies. Although our understanding of physiological and pathological roles of peripheral dopamine has been increasing rapidly in recent times, we still need more information to allow the design of clinically useful drugs that modify these roles. One priority is an orally-active selective dopamine D1 receptor agonist.
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PMID:The therapeutic potential of dopamine modulators on the cardiovascular and renal systems. 1199 45


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