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

MODIfY Trial
  • Sebastian Nuding
  • Henning Ebelt
  • Robert S. Hoke
  • Annette Krummenerl
  • Andreas Wienke
  • Ursula Müller-Werdan
  • Karl Werdan
Original Paper



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.


MODI fY 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.


The first patient was randomized on May 21, 2010.


The MODI fY trial is the first application of ivabradine as a pure heart rate reducing agent in MODS patients.


Heart rate Ivabradine Critically ill patient Multiple organ dysfunction syndrome 


Conflict of interest

The MODI fY study is an investigator-driven study which has been supported in part by Servier Company, the company producing ivabradine (Procoralan®). K.W. has received honoraria from Servier Company for lectures, national advisory board activities and participation in clinical trials (BEAUTIFUL, SHIFT, SIGNIFY); K.W. got also financial support from Servier Company for experimental research projects. The other authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sebastian Nuding
    • 1
  • Henning Ebelt
    • 1
  • Robert S. Hoke
    • 1
  • Annette Krummenerl
    • 2
  • Andreas Wienke
    • 3
  • Ursula Müller-Werdan
    • 1
  • Karl Werdan
    • 1
  1. 1.Department of Medicine III (Cardiology, Angiology, Medical Intensive Care Medicine, Geriatrics, Sports Medicine)University Clinics Halle (Saale), Medical Faculty of the Martin-Luther University Halle-WittenbergHalle (Saale)Germany
  2. 2.Coordination Centre for Clinical Trials Halle (Saale)Medical Faculty of the Martin-Luther-University Halle-WittenbergHalle (Saale)Germany
  3. 3.Institute of Medical Epidemiology, Biostatistics and InformaticsMedical Faculty of the Martin-Luther-University Halle-WittenbergHalle (Saale)Germany

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