| A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study. | |
| | |
MedLine Citation:
|
PMID: 17319797 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Etomoxir is an inhibitor of mitochondrial CPT1 (carnitine palmitoyltransferase 1) and thereby switches energy metabolism from fatty acids to glucose oxidation. Such a metabolic change may be beneficial in CHF (congestive heart failure). The ERGO (etomoxir for the recovery of glucose oxidation) study was designed in which etomoxir was tested at a dose of 80 and 40 mg compared with placebo for a period of 6 months in patients with CHF. As the principle measure of efficacy, a maximal exercise tolerance test and a submaximal 6-min corridor walk test were used. Secondary end points were echocardiographical dimensions and quality-of-life assessment scores. A total of 350 patients were planned to be screened, with the expectation that end point data would be available from approx. 260 patients. However, the study had to be stopped prematurely, because unacceptably high liver transaminase levels were detected in four patients taking etomoxir. At the termination of the study, 121 patients were randomized to placebo, 118 to 40 mg of etomoxir and 108 to 80 mg of etomoxir. At that time, 21 patients in the placebo group, 16 in the 40 mg of etomoxir group and 14 patients in the 80 mg of etomoxir group had completed the study. The mean increases in exercise time were 3.3, 10.2 and 19.4 s for the placebo, 40 mg of etomoxir and 80 mg of etomoxir groups respectively (P value was not significant). No changes were obvious in the 6-min corridor walk test or in echocardiographical parameters from baseline. The number of patients that completed the study was too small to demonstrate significant effects on exercise time, although there was a tendency towards an increase in exercise time. Therefore, before rejecting the hypothesis that inhibition of fatty acid oxidation might be beneficial in CHF, similar studies have to be performed using different inhibitors of fatty acid oxidation targeting CPT1 and other enzymes in this metabolic pathway. |
| | |
Authors:
|
Christian J F Holubarsch; Martin Rohrbach; Matthias Karrasch; Erich Boehm; Lech Polonski; Piotr Ponikowski; Siegfried Rhein |
Related Documents
:
|
2261147 - Quinapril in chronic heart failure. 19952837 - Upper intensity limit for prolonged aerobic exercise in chronic heart failure. 17037087 - Exercising with a denervated heart after cardiac transplantation. 17028107 - Gas diffusion and alveolar-capillary unit in chronic heart failure. 15604297 - Exercise-induced increase in skeletal muscle vasodilatory responses in obese zucker rats. 2730307 - Acute physiologic and perceptual responses during three modes of ambulation: walking, a... |
Publication Detail:
|
Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Clinical science (London, England : 1979) Volume: 113 ISSN: 1470-8736 ISO Abbreviation: Clin. Sci. Publication Date: 2007 Aug |
Date Detail:
|
Created Date: 2007-07-11 Completed Date: 2007-09-26 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 7905731 Medline TA: Clin Sci (Lond) Country: England |
Other Details:
|
Languages: eng Pagination: 205-12 Citation Subset: IM |
Affiliation:
|
Department of Cardiology, Hospital Lazariterhof and Baden, Median-Clinics Bad Krozingen, Bad Krozigen, Germany. c.holubarsch@median-bk.de |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Aged Aged, 80 and over Carnitine O-Palmitoyltransferase / antagonists & inhibitors Dose-Response Relationship, Drug Double-Blind Method Enzyme Inhibitors / administration & dosage*, adverse effects, therapeutic use Epoxy Compounds / administration & dosage*, adverse effects, therapeutic use Exercise Test Female Heart Failure / drug therapy*, physiopathology, ultrasonography Humans Liver / drug effects, enzymology Male Middle Aged Stroke Volume / drug effects Treatment Outcome |
| Chemical | |
Reg. No./Substance:
|
0/Enzyme Inhibitors; 0/Epoxy Compounds; 82258-36-4/etomoxir; EC 2.3.1.21/Carnitine O-Palmitoyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Superior survival and durability of neurons and astrocytes on 3-dimensional aragonite biomatrices.
Next Document: Adaptation of baroreflex function to increased carotid artery stiffening in patients with transposit...