Reducing elevated heart rate in patients with multiple organ dysfunction syndrome by the I (f) (funny channel current) inhibitor ivabradine : MODI (f)Y trial

Clin Res Cardiol. 2011 Oct;100(10):915-23. doi: 10.1007/s00392-011-0323-2. Epub 2011 Jun 3.

Abstract

Background: Heart rate (HR) is of relevant prognostic value not only in the general population and patients with cardiovascular disease, but also in critically ill patients with multiple organ dysfunction syndrome (MODS). An elevated HR in MODS patients is associated with a worse prognosis. Beta-blocker (BB) administration has been shown to reduce mortality in MODS. In most cases, negative inotropic effects prevent administration of BBs in MODS patients. In this trial we investigate, whether the "funny current" (I (f)) channel inhibitor ivabradine is able and apt to reduce pathologically elevated HR in MODS patients. We hypothesize that critically ill patients could derive particular benefit from the specific HR-lowering agent ivabradine.

Methods: MODI (f)Y is a prospective, single centre, open label, randomized, controlled two arms, phase II-trial to evaluate the potential of ivabradine to reduce an elevated HR in MODS patients. The primary end point is the proportion of patients with a reduction of HR by at least 10 beats per minute (bpm) within 4 days. This trial will randomize 70 patients (men and women, aged ≥18 years) with newly diagnosed MODS, with an elevated HR (sinus rhythm with HR ≥90 bpm) and contraindications to BB therapy. Treatment period will last for 4 days. All patients will be followed for 6 months.

Results: The first patient was randomized on May 21, 2010.

Conclusions: The MODI (f)Y trial is the first application of ivabradine as a pure heart rate reducing agent in MODS patients.

Trial registration: ClinicalTrials.gov NCT01186783.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists
  • Adult
  • Aged
  • Anti-Arrhythmia Agents / therapeutic use*
  • Benzazepines / therapeutic use*
  • Contraindications
  • Critical Illness
  • Cyclic Nucleotide-Gated Cation Channels / antagonists & inhibitors*
  • Cyclic Nucleotide-Gated Cation Channels / metabolism
  • Female
  • Germany
  • Heart Conduction System / drug effects*
  • Heart Conduction System / metabolism
  • Heart Conduction System / physiopathology
  • Heart Rate / drug effects*
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ivabradine
  • Male
  • Middle Aged
  • Multiple Organ Failure / drug therapy*
  • Multiple Organ Failure / metabolism
  • Multiple Organ Failure / physiopathology
  • Patient Selection
  • Potassium Channels / metabolism
  • Prospective Studies
  • Research Design*
  • Time Factors
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Anti-Arrhythmia Agents
  • Benzazepines
  • Cyclic Nucleotide-Gated Cation Channels
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Potassium Channels
  • Ivabradine

Associated data

  • ClinicalTrials.gov/NCT01186783