Reducing Elevated Heart Rate in Patients With Multiple Organ Dysfunction Syndrome (MODS) by the "Funny Channel" Current (If) Inhibitor Ivabradine
试验速览
- 阶段
- 2 期
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- mean heart rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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))
研究组 & 干预措施
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.
干预措施: ivabradine (Drug)
结局指标
主要结局
mean heart rate
时间窗: 4 days
percenage of patients with a reduction of the mean heart rate of at least 10 bpm 96 hours after the start of trial treatment
次要结局
- morbidity(4 days)
- hemodynamic parameters(4 days)
- catecholamine dosage(4 days)
- microcirculation(4 days)
- endothelial function(4 days)
- mean heart rate(48 hours)
- mortality(6 months)
- cardiac autonomic dysfunction(4 days)
- number of participants with adverse events as a measure of safety and tolerability(6 months)
- plasma levels of ivabradine in patients with MODS(4 days)
- Differences of mortality in different age groups and MODS groups(6 months)
- Differences of adverse events in different age groups and MODS groups(6 months)
- Differences of heart rate in different age groups and MODS groups(6 months)