NCT04031573

Ivabradine for Heart Rate Control In Septic Shock

A Multicenter, Prospective, Randomized, Placebo-controlled, Double-blind, Multi-arm, Multi-stage Clinical Trial of Ivabradine for Heart Rate Control In Septic Shock

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 429 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Septic shock is a major health problem, with several million cases annually worldwide and a mortality approaching 45%. Tachycardia is associated with excess mortality during septic shock. This pejorative effect could be related to the increase in cardiac metabolic demand, impaired cardiac diastolic function, and/or poorer tolerance of administered exogenous catecholamines. Recent studies suggest that controlling the heart rate with the use of beta blockers has beneficial effects on the morbidity and mortality of septic shock. However, the negative effects of beta-blockers on cardiac contractility and blood pressure complicate their use during septic shock, particularly because about one-half of patients exhibit a septic-associated systolic dysfunction, which often requires the use of inotropes. Ivabradine is a selective inhibitor of If channels in the sinoatrial node. It is a pure bradycardic agent with no deleterious effect on other aspects of cardiac function (contractility, conduction and repolarization) nor on blood pressure. Ivabradine can therefore alleviate sinus tachycardia without negative inotropic effects nor hypotension. Moreover, the improvement in diastolic function (ventricular filling) with ivabradine may increase stroke volume, even in case of severe impairment of systolic function. Controlling sinus tachycardia with ivabradine during septic shock would allow reducing cardiac metabolic demand (and potentially associated ischemic events) and improving the chronotropic tolerance of exogenous catecholamines. The effectiveness of ivabradine in controlling the heart rate was demonstrated in various clinical settings such as coronary artery disease, chronic heart failure and cardiogenic shock. Encouraging preliminary data are reported in critically ill patients.

Conditions

• Septic Shock

Interventions

Type	Name	Description
DRUG	Ivabradine	Ivabradine will be administered via the enteral route, every 12 hours, at doses ranging from 2.5 to 5 mg to achieve a target heart rate between 80 and 94 bpm
DRUG	Ivabradine	Ivabradine will be administered via the enteral route, every 12 hours, at doses ranging from 5 to 7.5 mg to achieve a target heart rate between 80 and 94
DRUG	Placebo	Placebo will be administered via the enteral route, every 12 hours.

Timeline

• Start date: 2021-02-26
• Primary completion: 2026-02-19
• Completion: 2026-04-22
• First posted: 2019-07-24
• Last updated: 2026-03-23

Locations

1 site across 1 country: France