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

Martin-Luther-Universität Halle-Wittenberg

Status and phase: Unknown; Phase 2

Conditions: Multiple Organ Dysfunction Syndrome

Treatments: Drug: ivabradine

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT01186783

KKSH-067

Details and patient eligibility

About

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.

Full 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.

Enrollment: 70 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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))

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

standard treatment

No Intervention group

Description:

All patients receive established medical therapy according to current guidelines and therapeutic standards.

ivabradine (add-on)

Active Comparator group

Description:

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.

Treatment:

Drug: ivabradine