Clinical trial • Phase III • Infectious Disease
Ivabradine hydrochloride for Septic shock
Phase III trial of Ivabradine hydrochloride for Septic shock.
Overview
- Trial Therapeutic Area
- Infectious Disease
- Trial Disease
- Septic shock
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 27-09-2024
- First CTIS Authorization Date
- 02-12-2024
Trial design
Randomised, placebo of procoralan 5 mg (placebo arm); procoralan 5 mg film-coated tablets (ivabradine hydrochloride) — two ivabradine arms. product information: procoralan 5 mg film-coated tablets (active substance ivabradine hydrochloride), max daily dose 7.5 mg, max treatment period 14 days. trial-specific dosing/schedule not specified in the record.-controlled, adaptive Phase III trial across 28 sites in France.
- Randomised
- Yes
- Comparator
- Placebo of Procoralan 5 mg (placebo arm); Procoralan 5 mg film-coated tablets (ivabradine hydrochloride) — two ivabradine arms. Product information: Procoralan 5 mg film-coated tablets (active substance ivabradine hydrochloride), max daily dose 7.5 mg, max treatment period 14 days. Trial-specific dosing/schedule not specified in the record.
- Adaptive
- Yes
- Target Sample Size
- 429
- Trial Duration For Participant
- 28
Eligibility
Recruits 429 Vulnerable population selected. Informed consent must be obtained in accordance with local regulations. Emergency inclusion/informed consent forms are provided (NIFC-adulte_FormulaireInclusionUrgence) and separate subject information and ICF documents exist for adult patients and for a legal representative/relative ("Proche") and continuation/follow-up forms, indicating procedures for obtaining consent/consent by proxy in this critically ill population..
- Pregnancy Exclusion
- Known pregnancy, breast feeding, women with childbearing potential will be tested for pregnancy and excluded if pregnant
- Vulnerable Population
- Vulnerable population selected. Informed consent must be obtained in accordance with local regulations. Emergency inclusion/informed consent forms are provided (NIFC-adulte_FormulaireInclusionUrgence) and separate subject information and ICF documents exist for adult patients and for a legal representative/relative ("Proche") and continuation/follow-up forms, indicating procedures for obtaining consent/consent by proxy in this critically ill population.
Inclusion criteria
- {"criterion_text":"- 18 years of age or older"}
- {"criterion_text":"- Proven or suspected site of infection"}
- {"criterion_text":"- Proven or suspected site of infection, -\tSeptic 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)"}
- {"criterion_text":"- In sinus rhythm with heart rate ≥ 95 bpm at time of randomization"}
- {"criterion_text":"- Informed consent obtained in accordance with local regulations"}
- {"criterion_text":"- Affiliation to a social security regime"}
Exclusion criteria
- {"criterion_text":"- Cardiac arythmia, conduction disorder, sinus syndrome (\"sick sinus syndrome\"), sino-atrial block; 3rd degree atrioventricular block"}
- {"criterion_text":"- Severe chronic renal failure (creatinine clearance <15 ml/min) or hepatic failure (prothrombin time <20%)"}
- {"criterion_text":"- Enteral feeding impossible, vomiting, congenital galactosemia, lactase deficiency, glucose-galactose malabsorption syndrome"}
- {"criterion_text":"- Tachycardia due to hyperthyroidism, pheochromocytoma or severe anemia (<7 g/dL)"}
- {"criterion_text":"- Prior enrolment in the trial, participation in another interventional study on septic shock"}
- {"criterion_text":"- Known legal incapacity (patients under guardianship or curatorship)"}
- {"criterion_text":"- Decision to limit full care taken before obtaining informed consent"}
- {"criterion_text":"- Patient under AME (state emergency medical help)"}
- {"criterion_text":"- Lack of affiliation to social security"}
- {"criterion_text":"- Cardiogenic shock or unstable or acute heart failure without proven or suspected infection"}
- {"criterion_text":"- Acute myocardial infarction with angiographic documentation; CCS class ≥ II angina pectoris;"}
- {"criterion_text":"- Septic shock requiring vasopressor treatment for more than 24 hours"}
- {"criterion_text":"- 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)"}
- {"criterion_text":"- Co-treatment with drugs inducing bradycardia, QT lengthening or strong inhibition of CYP4503A4, pacemaker, defibrillator, kalemia <3 mM"}
- {"criterion_text":"- Co-treatment with verapamil or diltiazem (which are moderate CYP4503A4 inhibitors with heart rate reducing properties)"}
- {"criterion_text":"- Known allergy to ivabradine or to any of the excipients, retinitis pigmentosa, congenital galactosemia, lactase deficiency, glucose or galactose malabsorption"}
Endpoints
Primary endpoints
- {"endpoint_text":"- i) for treatment selection at interim analysis: the percentage of patients with heart rate within the predefined threshold (80-94 bpm) at hour-48; in case of similar percentages, the percentage of time elapsed within the threshold between inclusion and hour-48 will be considered","definition_or_measurement_approach":"Percentage of patients with heart rate within 80-94 bpm at hour 48; if percentages are similar between arms the tie-breaker is the percentage of time within the threshold between inclusion and hour-48."}
- {"endpoint_text":"- ii) for the final analysis: 28-day mortality.","definition_or_measurement_approach":"All-cause mortality assessed at day 28."}
Secondary endpoints
- {"endpoint_text":"- Determine the tolerance of ivabradine","definition_or_measurement_approach":"Not specified in the provided record."}
- {"endpoint_text":"- Evaluate the impact of ivabradine-driven heart rate control on systemic hemodynamics, myocardial stress, organ dysfunction, morbidity, and intensive care mortality","definition_or_measurement_approach":"Not specified in the provided record; endpoint describes clinical outcomes and hemodynamic/organ dysfunction measures."}
- {"endpoint_text":"- Determine the pharmacokinetics of ivabradine","definition_or_measurement_approach":"PK parameters to be determined (details not provided in the record)."}
Recruitment
- Planned Sample Size
- 429
- Recruitment Window Months
- 63
- Consent Approach
- Informed consent obtained in accordance with local regulations. The submission includes subject information and informed consent forms for adults, emergency inclusion form (NIFC-adulte_FormulaireInclusionUrgence), ICFs for patient and for a legal representative/relative (Proche), and continuation/follow-up ICFs, indicating procedures to obtain consent or consent by proxy in emergency/critically ill settings. Language availability not fully specified in the record (translations available in French).
Geography
- Total Number Of Sites
- 28
- Total Number Of Participants
- 429
France
- Earliest CTIS Part Ii Submission Date
- 04-10-2024
- Latest Decision Or Authorization Date
- 07-01-2026
- Processing Time Days
- 460
- Number Of Sites
- 28
- Number Of Participants
- 429
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Médecine Intensive Réanimation
- Principal Investigator Name
- Antoine VIEILLARD-BARON
- Principal Investigator Email
- antoine.vieillard-baron@aphp.fr
- Contact Person Name
- Antoine VIEILLARD-BARON
- Contact Person Email
- antoine.vieillard-baron@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- Service des maladies infectieuses et réanimation médicale
- Principal Investigator Name
- Pauline GUILLOT
- Principal Investigator Email
- pauline.guillot@chu-rennes.fr
- Contact Person Name
- Pauline GUILLOT
- Contact Person Email
- pauline.guillot@chu-rennes.fr
- Site Name
- Hospital Foch
- Department Name
- Réanimation polyvalente et ISU neurochirurgicale
- Principal Investigator Name
- Charles CERF
- Principal Investigator Email
- c.cerf@hopital-foch.org
- Contact Person Name
- Charles CERF
- Contact Person Email
- c.cerf@hopital-foch.org
- Site Name
- Centre Hospitalier Regional Universitaire De Tours
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Sophie JACQUIER
- Principal Investigator Email
- s.jacquier@chu-tours.fr
- Contact Person Name
- Sophie JACQUIER
- Contact Person Email
- s.jacquier@chu-tours.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Médecine Intensive Réanimation
- Principal Investigator Name
- Charles-Edouard LUYT
- Principal Investigator Email
- charles-edouard.luyt@aphp.fr
- Contact Person Name
- Charles-Edouard LUYT
- Contact Person Email
- charles-edouard.luyt@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation médico-chirurgicale
- Principal Investigator Name
- Cyrielle DESNOS
- Principal Investigator Email
- cyrielle.desnos@aphp.fr
- Contact Person Name
- Cyrielle DESNOS
- Contact Person Email
- cyrielle.desnos@aphp.fr
- Site Name
- Centre Hospitalier Universitaire Amiens Picardie
- Department Name
- Médecine intensive Réanimation
- Principal Investigator Name
- Michel SLAMA
- Principal Investigator Email
- s.michel@chu-amiens.fr
- Contact Person Name
- Michel SLAMA
- Contact Person Email
- s.michel@chu-amiens.fr
- Site Name
- Hôpital Saint Camille
- Department Name
- Service d’Anesthésie-Réanimation
- Principal Investigator Name
- Serge CARREIRA
- Principal Investigator Email
- s.carreira@cch-bry.org
- Contact Person Name
- Serge CARREIRA
- Contact Person Email
- s.carreira@cch-bry.org
- Site Name
- Les Hopitaux Universitaires De Strasbourg
- Department Name
- Service de Médecine Intensive-Réanimation
- Principal Investigator Name
- Julie HELMS
- Principal Investigator Email
- julie.helms@chu-strasbourg.fr
- Contact Person Name
- Julie HELMS
- Contact Person Email
- julie.helms@chu-strasbourg.fr
- Site Name
- Les Hopitaux Universitaires De Strasbourg
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Vincent CASTELAIN
- Principal Investigator Email
- vincent.castelain@chru-strasbourg.fr
- Contact Person Name
- Vincent CASTELAIN
- Contact Person Email
- vincent.castelain@chru-strasbourg.fr
- Site Name
- Centre Hospitalier Universitaire De Poitiers
- Department Name
- Service de Médecine Intensive et Réanimation
- Principal Investigator Name
- Florence BOISSIER
- Principal Investigator Email
- florence.boissier@chu-poitiers.fr
- Contact Person Name
- Florence BOISSIER
- Contact Person Email
- florence.boissier@chu-poitiers.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation médicale
- Principal Investigator Name
- Xavier MONNET
- Principal Investigator Email
- xavier.monnet@aphp.fr
- Contact Person Name
- Xavier MONNET
- Contact Person Email
- xavier.monnet@aphp.fr
- Site Name
- Centre Hospitalier Saint Joseph Saint Luc
- Department Name
- Réanimation Polyvalente
- Principal Investigator Name
- Emmanuel VIVIER
- Principal Investigator Email
- evivier@ch-stjoseph-stluc-lyon.fr
- Contact Person Name
- Emmanuel VIVIER
- Contact Person Email
- evivier@ch-stjoseph-stluc-lyon.fr
- Site Name
- Centre Hospitalier Regional Et Universitaire De Brest
- Department Name
- Réanimation médicale
- Principal Investigator Name
- Gwenael PRAT
- Principal Investigator Email
- gwenael.prat@chu-brest.fr
- Contact Person Name
- Gwenael PRAT
- Contact Person Email
- gwenael.prat@chu-brest.fr
- Site Name
- Hopitaux Prives De Metz
- Department Name
- Service de Réanimation Polyvalente
- Principal Investigator Name
- Peter ESZTO
- Principal Investigator Email
- peter.eszto@uneos.fr
- Contact Person Name
- Peter ESZTO
- Contact Person Email
- peter.eszto@uneos.fr
- Site Name
- Grand Hopital De L Est Francilien
- Department Name
- Médecine intensive et réanimation
- Principal Investigator Name
- Frank CHEMOUNI
- Principal Investigator Email
- frank.chemouni@gmail.com
- Contact Person Name
- Frank CHEMOUNI
- Contact Person Email
- frank.chemouni@gmail.com
- Site Name
- Groupe Hospitalier Du Sud Ile De France
- Department Name
- Service de Réanimation
- Principal Investigator Name
- Oumar SY
- Principal Investigator Email
- oumar.sy@ghsif.fr
- Contact Person Name
- Oumar SY
- Contact Person Email
- oumar.sy@ghsif.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation médicale et infectieuse
- Principal Investigator Name
- Romain SONNEVILLE
- Principal Investigator Email
- romain.sonneville@aphp.fr
- Contact Person Name
- Romain SONNEVILLE
- Contact Person Email
- romain.sonneville@aphp.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Service de Médecine Intensive-Réanimation
- Principal Investigator Name
- Laurent ARGAUD
- Principal Investigator Email
- laurent.argaud@chu-lyon.fr
- Contact Person Name
- Laurent ARGAUD
- Contact Person Email
- laurent.argaud@chu-lyon.fr
- Site Name
- Centre Hospitalier Sud Francilien
- Department Name
- Réanimation Polyvalente
- Principal Investigator Name
- Cécilia BILLIOU
- Principal Investigator Email
- unite.rechercheclinique@chsf.fr
- Contact Person Name
- Cécilia BILLIOU
- Contact Person Email
- unite.rechercheclinique@chsf.fr
- Site Name
- Centre Hospitalier Intercommunal De Poissy Saint Germain
- Department Name
- Service de Médecine intensive- réanimation
- Principal Investigator Name
- Nesrine FRAJ
- Principal Investigator Email
- Nesrine.fraj@ght-yvelinesnord.fr
- Contact Person Name
- Nesrine FRAJ
- Contact Person Email
- Nesrine.fraj@ght-yvelinesnord.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service d’Anesthésie-Réanimation
- Principal Investigator Name
- Bernard CHOLLEY
- Principal Investigator Email
- bernard.cholley@aphp.fr
- Contact Person Name
- Bernard CHOLLEY
- Contact Person Email
- bernard.cholley@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Nice
- Department Name
- Service de Médecine Intensive Réanimation
- Principal Investigator Name
- Denis DOYEN
- Principal Investigator Email
- doyen.d@chu-nice.fr
- Contact Person Name
- Denis DOYEN
- Contact Person Email
- doyen.d@chu-nice.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation Médicale et toxicologique
- Principal Investigator Name
- Nicolas DEYE
- Principal Investigator Email
- nicolas.deye@aphp.fr
- Contact Person Name
- Nicolas DEYE
- Contact Person Email
- nicolas.deye@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Réanimation Médicale
- Principal Investigator Name
- Armand MEKONTSO-DESSAP
- Principal Investigator Email
- armand.dessap@aphp
- Contact Person Name
- Armand MEKONTSO-DESSAP
- Contact Person Email
- armand.dessap@aphp
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service de Réanimation Médico-chirurgicale
- Principal Investigator Name
- Djillali ANNANE
- Principal Investigator Email
- djillali.annane@aphp.fr
- Contact Person Name
- Djillali ANNANE
- Contact Person Email
- djillali.annane@aphp.fr
- Site Name
- Centre Hospitalier Victor Dupouy
- Department Name
- Service de Réanimation Polyvalente
- Principal Investigator Name
- Damien CONTOU
- Principal Investigator Email
- damien.contou@ch-argenteuil.fr
- Contact Person Name
- Damien CONTOU
- Contact Person Email
- damien.contou@ch-argenteuil.fr
- Site Name
- University Hospital Of Clermont-Ferrand
- Department Name
- Service de Médecine Intensive et Réanimation
- Principal Investigator Name
- Claire DUPUIS
- Principal Investigator Email
- cdupuis1@chu-clermondferrand.fr
- Contact Person Name
- Claire DUPUIS
- Contact Person Email
- cdupuis1@chu-clermondferrand.fr
Sponsor
Primary sponsor
- Full Name
- Assistance Publique Hopitaux De Paris
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- France
Investigational products
- Investigational Product Name
- Procoralan 5 mg film-coated tablets
- Active Substance
- Ivabradine hydrochloride
- Modality
- Small molecule
- Routes Of Administration
- ENTERAL FEEDING TUBE (film-coated tablet/oral formulation)
- Route
- Enteral (tablet) / Enteral feeding tube
- Authorisation Status
- Authorised (marketing authorisation EU/1/05/316/007)
- Maximum Dose
- 7.5 mg per day
- Investigational Product Name
- Placebo of Procoralan 5 mg
- Modality
- Other
Related trials
Other published trials that may interest you.