Efficacy of zoniporide, an Na/H exchange ion inhibitor, for reducing perioperative cardiovascular events in vascular surgery patients

Lee A. Fleisher, Mark F. Newman, Lisa B. St. Aubin, Anne B. Cropp, C. Bill Billing, Sharon Bonney, William C. Mackey, Don Poldermans, Roman Corbalan, Adamastor H. Pereira, Pierre Coriat

Research output: Contribution to journalArticle

Abstract

Objectives: To determine whether a novel Na+/H+ exchange ion inhibitor, zoniporide, is associated with reduced perioperative myocardial ischemic injury in high-risk surgery patients. Design: Randomized double-blind placebo-controlled multidose trial. Setting: Multicenter worldwide (105 centers) trial. Participants: Patients with known or multiple risk factors for coronary artery disease undergoing noncardiac vascular surgery. Interventions: Four parallel groups received 1 of 3 doses of zoniporide or placebo, delivered as a 60-minute loading dose immediately before surgery, and followed by a continuous intravenous infusion for up to 7 days. Measurements and Main Results: A total of 824 subjects were randomized into the study from 105 centers worldwide. Of these, 784 subjects received study drug infusion in the 3-mg/kg/d, 6-mg/kg/d, and 12-mg/kg/d groups and the placebo group, and 769 satisfied the criteria for the primary efficacy analysis population. This is 68% of the planned sample size of 1125 subjects. Anesthetic management and perioperative cardiac medications were at the discretion of the attending anesthesiologists, surgeons, and cardiologists. The proportion of subjects who experienced the composite endpoint event (death, myocardial infarction, congestive heart failure, arrhythmia) by postsurgical day 30 was 18.5% in the 12-mg/kg/d group, compared with 15.7% in the placebo group, resulting in a relative risk (RR) of 1.17% (95% confidence interval [CI], 0.80-1.72; p = NS) favoring placebo. The proportions in the lower 2 zoniporide dose groups were slightly lower than in the placebo group, although the sample size is inadequate to reach any firm conclusions. Conclusions: The results fail to demonstrate the efficacy of zoniporide in reducing the proportion of patients at high risk undergoing noncardiac vascular surgery who experience a composite cardiovascular endpoint, which led the corporate sponsor to stop enrollment early on the basis of a futility analysis of the chance of demonstrating efficacy with a larger sample size.

Original languageEnglish (US)
Pages (from-to)570-576
Number of pages7
JournalJournal of cardiothoracic and vascular anesthesia
Volume19
Issue number5
DOIs
StatePublished - Oct 1 2005

Keywords

  • Arrhythmia
  • Outcome
  • Perioperative myocardial ischemia
  • Randomized controlled trial
  • Sodium-hydrogen exchanger
  • Vascular surgery

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Anesthesiology and Pain Medicine

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  • Cite this

    Fleisher, L. A., Newman, M. F., St. Aubin, L. B., Cropp, A. B., Billing, C. B., Bonney, S., Mackey, W. C., Poldermans, D., Corbalan, R., Pereira, A. H., & Coriat, P. (2005). Efficacy of zoniporide, an Na/H exchange ion inhibitor, for reducing perioperative cardiovascular events in vascular surgery patients. Journal of cardiothoracic and vascular anesthesia, 19(5), 570-576. https://doi.org/10.1053/j.jvca.2005.06.012