Reducing Elevated Heart Rate in Patients With Severe Sepsis by Ivabradine

Study Overview
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Brief Summary
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REHSI is a prospective, multi-center, open label, randomized, controlled two arms, to evaluate the ability of ivabradine to reduce an elevated heart rate in septic shock patients. The primary end point is the reduction of heart rate within 24 hours. This trial will randomize 70 patients (men and women, aged ≥ 18 years) with newly diagnosed Septic Shock (despite adequate fluid resuscitation, were still requiring high-dose norepinephrine (NE) to maintain a mean arterial pressure (MAP) ≥65 mmHg , and had a tachycardia >100 beats per minute (bpm). Treatment period will last 4 days. All patients will be followed for up to six months.

Official Title
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Reducing Elevated Heart Rate in Patients With Severe Sepsis by by the Funny Channel Current (If) Inhibitor Ivabradine

Conditions
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Sepsis, Severe

Intervention / Treatment
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* Drug: Ivabradine Oral Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe sepsis due to coronary and non-coronary etiology Severe sepsis diagnosed ≤ 24 h Sinus rhythm with heart rate ≥ 100bpm 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 severe hepatic insufficiency Sick sinus syndrome Sinu-atrial block pacemaker-dependency 8.3rd degree AV block 9.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))

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ivabradine oral product<br>Patients in the ivabradine treatment arm receive interventions:an additional enteral preparation (orally, via nasogastric tube or Jejunum tube) of ivabradine for 4 days. | Drug: Ivabradine Oral Product<br>* Patients in the ivabradine treatment arm receive an additional enteral preparation (orally, via nasogastric tube or Jejunum tube) of ivabradine for 4 days. Day 1 : 2.5 mg ivabradine b.i.d. if heart rate ≥90 bpm Day 2,3,4: 2.5 mg ivabradine b.i.d. if 60bpm≥heart rate<90bpm. 5.0mg ivabradine b.i.d. if heart rate ≥90bpm<br>* Other names: routine therapy;|
| No Intervention: control group<br>All patients receive established medical therapy according to current guidelines and therapeutic standards. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean heart rate | the reduction of the mean heart rate of 24 hours after the start of trial treatment | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| severity of illness | measured by serial APACHE II score monitoring and Sequential Organ Failure Sequential Organ Failure Assessment (SOFA) score monitoringAssessment (SOFA) score monitoring | 4 days | 
| mean heart rate | comparison of the mean heart rate between the treatment and control group | 4 days | 
| mortality | 28-day and 6 months mortality | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ivabradine, sepsis, heart rate