Reducing Elevated Heart Rate in Patients With Severe Sepsis by Ivabradine

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

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.

Inclusion Criteria:

1. Severe sepsis due to coronary and non-coronary etiology
2. Severe sepsis diagnosed ≤ 24 h
3. Sinus rhythm with heart rate ≥ 100bpm
4. Written informed consent or identified or suspected positive will with respect to the trial treatment

Exclusion Criteria:

1. Patients who have not yet completed the 18th year of age
2. Pregnancy, lactation
3. Patients with a history of pre-existing chronic renal failure with a glomerular filtration rate <30ml/min
4. severe hepatic insufficiency
5. Sick sinus syndrome
6. Sinu-atrial block
7. 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))