Using Ivabradine to Control Heart Rate 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
This study is testing if the heart medication Ivabradine can help people in septic shock by controlling their heart rate and improving their chances of recovery.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 429 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Locations | 1 site (Créteil) |
| Trial ID | NCT04031573 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the use of Ivabradine, a selective inhibitor of If channels, to manage heart rate in patients experiencing septic shock. Septic shock is a critical condition characterized by severe infection and low blood pressure, often leading to high mortality rates. The study aims to determine if controlling heart rate with Ivabradine can improve patient outcomes without the adverse effects associated with beta-blockers. Participants will be randomized to receive either Ivabradine or a placebo while being monitored for their response to treatment.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with septic shock and a heart rate of 95 bpm or higher.
Not a fit: Patients under 18 years old or those with specific cardiac conditions such as arrhythmias or cardiogenic shock may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly reduce mortality and improve recovery in patients suffering from septic shock.
How similar studies have performed: Previous studies have shown that controlling heart rate in septic shock can be beneficial, but the use of Ivabradine specifically is a novel approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* 18 years of age or older,
* Proven or suspected site of infection,
* Septic shock (defined as hypotension unresponsive to fluid resuscitation and requiring vasopressor treatment to maintain adequate blood pressure in the context of proven or suspected site of infection) for at least 2 hours and less than 24 hours (inclusion is possible before 2 hours in case of increasing doses of norepinephrine),
* In sinus rhythm with heart rate ≥ 95 bpm at time of randomization,
* Informed consent obtained in accordance with local regulations,
* Affiliation to a social security regime.
Exclusion Criteria:
* Age \< 18 years,
* Cardiac arythmia, conduction disorder, sinus syndrome ("sick sinus syndrome"), sino-atrial block; 3rd degree atrioventricular block, "IRISS" protocol, version 6.0 of 30/10/2023 7/47 This document is the property of DRCD / APHP. All reproduction is strictly prohibited.
* Cardiogenic shock or unstable or acute heart failure without proven or suspected infection,
* Acute myocardial infarction with angiographic documentation; CCS class
≥ II angina pectoris;
* Septic shock requiring vasopressor treatment for more than 24 hours,
* Refractory shock with systolic arterial pressure \<90 mm Hg) despite the use of high doses of vasopressors (norepinephrine BASE or epinephrine BASE \> 2.4 µg/kg/min; these doses should be multiplied by two for noradrenaline salt (tartrate or bitartrate),
* Co-treatment with drugs inducing bradycardia, QT lengthening or strong inhibition of CYP4503A4, pacemaker, defibrillator, kalemia \<3 mM,
* Co-treatment with verapamil or diltiazem (which are moderate CYP4503A4 inhibitors with heart rate reducing properties)
* Known pregnancy, breast feeding, women with childbearing potential will be tested for pregnancy and excluded if pregnant,
* Known allergy to ivabradine or to any of the excipients, retinitis pigmentosa, congenital galactosemia, lactase deficiency, glucose or galactose malabsorption,
* Severe chronic renal failure (creatinine clearance \<15 ml/min) or hepatic failure (prothrombin time \<20%),
* Enteral feeding impossible, vomiting, congenital galactosemia, lactase deficiency, glucose-galactose malabsorption syndrome,
* Tachycardia due to hyperthyroidism, pheochromocytoma or severe anemia (\<7 g/dL),
* Prior enrolment in the trial, participation in another interventional study on septic shock,
* Known legal incapacity (patients under guardianship or curatorship),
* Decision to limit full care taken before obtaining informed consent,
* Patient under AME (state emergency medical help),
* Lack of affiliation to social security.
Where this trial is running
Créteil
- Henri Mondor Hospital — Créteil, France (Recruiting)
Study contacts
- Study coordinator: Armand MEKONTSO DESSAP, MD, PhD
- Email: armand.dessap@aphp.fr
- Phone: 01 49 81 23 89
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.