Sepsis, Severe
Conditions
Keywords
ivabradine, sepsis, heart rate
Brief summary
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.
Interventions
DRUGIvabradine Oral Product
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
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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))
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| mean heart rate | 24 hours | the reduction of the mean heart rate of 24 hours after the start of trial treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| severity of illness | 4 days | measured by serial APACHE II score monitoring and Sequential Organ Failure Sequential Organ Failure Assessment (SOFA) score monitoringAssessment (SOFA) score monitoring |
| mean heart rate | 4 days | comparison of the mean heart rate between the treatment and control group |
| mortality | 6 months | 28-day and 6 months mortality |
Outcome results
None listed