Reducing Elevated Heart Rate in Patients With Severe Sepsis by Ivabradine (REHSI)

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.

Study Overview

• Status: Unknown
• Conditions: Sepsis, Severe
• Intervention / Treatment: Drug: Ivabradine Oral Product

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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))

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ivabradine oral product; 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; 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; Other Names: routine therapy
No Intervention: control group; All patients receive established medical therapy according to current guidelines and therapeutic standards.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2018
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: October 1, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (Actual): December 8, 2017

Study Record Updates

• Last Update Posted (Actual): December 8, 2017
• Last Update Submitted That Met QC Criteria: December 4, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: sepsis; ivabradine; heart rate
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: REHSI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No