Reducing Elevated Heart Rate in Patients With Multiple Organ Dysfunction Syndrome (MODS) by Ivabradine (MODIfY)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Martin-Luther-Universität Halle-Wittenberg.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Servier
KKS Netzwerk
Information provided by:
Martin-Luther-Universität Halle-Wittenberg
ClinicalTrials.gov Identifier:
NCT01186783
First received: August 17, 2010
Last updated: September 7, 2010
Last verified: September 2010
  Purpose

MODIfY is a prospective, single center, open label, randomized, controlled two arms, Phase II-trial to evaluate the ability of ivabradine to reduce an elevated heart rate in Multiple Organ Dysfunction Syndrome (MODS) patients. The primary end point is the proportion of patients with a reduction of heart rate 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 (Acute Physiology and Chronic Health Evaluation (APACHE) II-score ≥ 20, diagnosis within ≤ 24 hours), with an elevated heart rate (sinus rhythm with HR ≥ 90 bpm) and contraindications to beta-blockers (BBs). Treatment period will last 4 days. All patients will be followed for up to six months.


Condition Intervention Phase
Multiple Organ Dysfunction Syndrome
Drug: ivabradine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reducing Elevated Heart Rate in Patients With Multiple Organ Dysfunction Syndrome (MODS) by the "Funny Channel" Current (If) Inhibitor Ivabradine

Resource links provided by NLM:


Further study details as provided by Martin-Luther-Universität Halle-Wittenberg:

Primary Outcome Measures:
  • mean heart rate [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    percenage of patients with a reduction of the mean heart rate of at least 10 bpm 96 hours after the start of trial treatment


Secondary Outcome Measures:
  • morbidity [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    group-differences and patient-related changes of morbidity measured by serial APACHE II score monitoring and Sequential Organ Failure Assessment (SOFA) score monitoring

  • hemodynamic parameters [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    group-differences and patient-related changes of hemodynamic parameters (cardiac index and cardiac power index) as a consequence of ivabradine treatment

  • catecholamine dosage [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    required catecholamine dosage measured by a vasopressor score

  • microcirculation [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    improvement of microcirculation as measured by sublingual capillary density and flow

  • endothelial function [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    improvement of endothelial function as measured by the "Reactive hyperemia peripheral arterial tonometry-index"

  • mean heart rate [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    comparison of the mean heart rate between the treatment and control group after 24 and 48 hours

  • mortality [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    28-day and 6 months mortality

  • cardiac autonomic dysfunction [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    impact on cardiac autonomic dysfunction (heart rate variability quantified by time domain measurements (standard deviation of normal to normal interval (SDNN)) and frequency domain measurements (very low frequency (VLF)-, high frequency (HF)- and low frequency (LF)-power) as well as minimum, maximum, day and night heart rate)

  • number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • plasma levels of ivabradine in patients with MODS [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    daily measurement of plasma levels during the treatment period (4 days)

  • Differences of mortality in different age groups and MODS groups [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    age sub-groups:

    1. patients <70 years on day of inclusion
    2. patients ≥70 years on day of inclusion

    MODS sub-groups:

    1. patients with cardiogenic MODS
    2. patients with septic MODS

  • Differences of adverse events in different age groups and MODS groups [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    age sub-groups:

    1. patients <70 years on day of inclusion
    2. patients ≥70 years on day of inclusion

    MODS sub-groups:

    1. patients with cardiogenic MODS
    2. patients with septic MODS

  • Differences of heart rate in different age groups and MODS groups [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    age sub-groups:

    1. patients <70 years on day of inclusion
    2. patients ≥70 years on day of inclusion

    MODS sub-groups:

    1. patients with cardiogenic MODS
    2. patients with septic MODS


Estimated Enrollment: 70
Study Start Date: May 2010
Estimated Study Completion Date: May 2012
Estimated Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: standard treatment
All patients receive established medical therapy according to current guidelines and therapeutic standards.
Active Comparator: ivabradine (add-on)
Patients in the ivabradine treatment arm receive an additional enteral preparation (orally, via nasogastric tube or percutaneous endoscopic gastrostomy-probe) of ivabradine for 4 days.
Drug: ivabradine

Patients in the ivabradine treatment arm receive an additional enteral preparation (orally, via nasogastric tube or percutaneous endoscopic gastrostomy-probe) of ivabradine for 4 days.

Day 1 and 2:

5,0 mg ivabradine b.i.d. if heart rate ≥60bpm (acute renal failure: ≥70bpm)

Day 3 and 4:

5,0 mg ivabradine b.i.d. if 60bpm≥heart rate<90bpm (acute renal failure: 70bpm≥heart rate <90bpm

7,5 mg ivabradine b.i.d. if heart rate ≥90bpm

Other Name: Procoralan

Detailed Description:

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). A raised heart rate in MODS patients is associated with a worse prognosis. Beta-blocker (BB) administration showed to improve autonomic function and exhibited a significantly reduced mortality in MODS. In most cases negative inotropic effects prevent administration of BB in MODS patients which often are treated with catecholamines. In this trial we investigate, whether the "funny current" (If) inhibitor ivabradine is able to reduce pathologically elevated heart rate in MODS- patients.

The investigators hypothesized that critically ill patients could derive particular benefit from the specific HR-lowering agent ivabradine.

Methods: MODIfY is a prospective, single center, open label, randomized, controlled two arms, Phase II-trial to evaluate the ability of ivabradine to reduce an elevated heart rate in MODS patients. The primary end point is the proportion of patients with a reduction of heart rate 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 (Acute Physiology and Chronic Health Evaluation (APACHE) II-score ≥20, diagnosis within ≤24 hours), with an elevated heart rate (sinus rhythm with HR ≥90 bpm) and contraindications to BBs. Treatment period will last 4 days. All patients will be followed for up to six months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Multiple organ dysfunction syndrome (APACHE II score ≥ 20) due to coronary and non-coronary etiology
  • Multiple organ dysfunction syndrome diagnosed ≤ 24 h
  • Sinus rhythm with heart rate ≥ 90bpm
  • Existing contraindications to beta-receptor blockade
  • Written informed consent or identified or suspected positive will with respect to the trial treatment

Exclusion Criteria:

  • Patients who have not yet completed the 18th year of age
  • Pregnancy, lactation
  • Patients with a history of pre-existing chronic renal failure with a glomerular filtration rate <30ml/min
  • Patients with malignant hyperthermia
  • Burn patients
  • Patients with acute rejection after organ transplantation
  • Patients with bleedings and need for transfusion
  • Resuscitated patients with suspected hypoxic brain injury
  • Patients who have participated or participate in other studies within the last 3 months
  • Other types of shock than septic or cardiogenic shock
  • Patients with severe valvular heart disease
  • Hypersensitivity to the active substance or any of the excipients
  • Severe hepatic insufficiency
  • Sick sinus syndrome
  • Sinu-atrial block
  • pacemaker-dependency
  • 3rd degree AV block
  • Use of potent cytochrome P450 3A4 inhibitors such as antifungals of the azole -type (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin per os, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone (see Summary of Product Characteristics (SPC))
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01186783

Contacts
Contact: Karl Werdan, MD, Professor 0049 345 557 ext 2601 karl.werdan@medizin.uni-halle.de

Locations
Germany
Department of Medicine III of the University Clinics Halle (Saale) of the Martin-Luther-University Halle-Wittenberg Recruiting
Halle (Saale), Saxony-Anhalt, Germany, 06120
Contact: Karl Werdan, MD, Professor    0049 345 557 ext 2601    karl.werdan@medizin.uni-halle.de   
Sponsors and Collaborators
Martin-Luther-Universität Halle-Wittenberg
Servier
KKS Netzwerk
Investigators
Study Chair: Karl Werdan, MD, Professor Medical Faculty of the Martin-Luther-University Halle-Wittenberg, Germany
Principal Investigator: Henning Ebelt, MD Medical Faculty of the Martin-Luther-University Halle-Wittenberg, Germany
Principal Investigator: Sebastian Nuding, MD Medical Faculty of the Martin-Luther-University Halle-Wittenberg, Germany
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Karl Werdan, MD, Professor, Medical Faculty of the Martin-Luther-University Halle-Wittenberg, Germany
ClinicalTrials.gov Identifier: NCT01186783     History of Changes
Other Study ID Numbers: KKSH-067
Study First Received: August 17, 2010
Last Updated: September 7, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Martin-Luther-Universität Halle-Wittenberg:
heart rate
multiple organ dysfunction syndrome
ivabradine
sepsis
cardiogenic shock

Additional relevant MeSH terms:
Multiple Organ Failure
Shock
Pathologic Processes

ClinicalTrials.gov processed this record on August 28, 2014