Clinical trial • Phase III • Cardiology
LEVOSIMENDAN for Cardiogenic shock
Phase III trial of LEVOSIMENDAN for Cardiogenic shock.
Overview
- Trial Therapeutic Area
- Cardiology
- Trial Disease
- Cardiogenic shock
- Trial Stage
- Phase III
- Drug Modality
- Small molecule|Peptide/protein/enzyme
Key dates
- Initial CTIS Submission Date
- 09-07-2024
- First CTIS Authorization Date
- 01-08-2024
Trial design
Randomised, placebo control (cernevit or soluvit) administered as intravenous infusion; specific placebo dose/schedule not specified in ctis record. Phase III trial across 29 sites in France.
- Randomised
- Yes
- Comparator
- Placebo control (CERNEVIT or SOLUVIT) administered as intravenous infusion; specific placebo dose/schedule not specified in CTIS record.
- Target Sample Size
- 610
- Trial Duration For Participant
- 365
Eligibility
Recruits 610 Vulnerable populations are addressed: minors are excluded ("Minor (not emancipated)"), persons deprived of liberty are excluded ("Person deprived of liberty for judicial or administrative decision"), and adults under legal protection are excluded ("Adult subject to a legal protection measure (such as guardianship, conservatorship)"). Informed consent documents are provided (multiple L1_SIS and ICF documents including versions for adults and for family/person of trust and an attestation for inclusion), indicating consent is obtained from the adult subject; there are ICFs for family/person of trust and procedures for inclusion continuation (documents listed: L1_SIS and ICF famille_personne de confiance, L1_SIS and ICF Adulte, L1_SIS and ICF_patient decede, L1_SIS and ICF poursuite Adulte, L1_SIS and ICF_poursuite_famille_personne de confiance, L1_ICF_Attestation inclusion SUVI). No assent process for minors is applicable since minors are excluded. Languages available are not specified..
- Pregnancy Exclusion
- Pregnant woman, birthing or breastfeeding mother
- Vulnerable Population
- Vulnerable populations are addressed: minors are excluded ("Minor (not emancipated)"), persons deprived of liberty are excluded ("Person deprived of liberty for judicial or administrative decision"), and adults under legal protection are excluded ("Adult subject to a legal protection measure (such as guardianship, conservatorship)"). Informed consent documents are provided (multiple L1_SIS and ICF documents including versions for adults and for family/person of trust and an attestation for inclusion), indicating consent is obtained from the adult subject; there are ICFs for family/person of trust and procedures for inclusion continuation (documents listed: L1_SIS and ICF famille_personne de confiance, L1_SIS and ICF Adulte, L1_SIS and ICF_patient decede, L1_SIS and ICF poursuite Adulte, L1_SIS and ICF_poursuite_famille_personne de confiance, L1_ICF_Attestation inclusion SUVI). No assent process for minors is applicable since minors are excluded. Languages available are not specified.
Inclusion criteria
- {"criterion_text":"- Adult patient ≥ 18 years with cardiogenic shock\n- Adequate intravascular volume\n- Norepinephrine to maintain MAP at least at 65 mmHg for at least 3 hours and less than 24h. At inclusion the dose must be <1 microgram/kg/min under norepinephrine base or <2 microgram/kg/min under norepinephrine tartrate, OR/AND Dobutamine since at least 3h and less than 24h at inclusion.\n- Tissue hypoperfusion: at least 1 sign with in 24 hours prior to inclusion (lactate ≥ 2 mmol/l; mottling, capillary refeel time > 3 seconds, oliguria <500ml/24h or ≤ 20 ml/h during the last 2 hours, ScVO2 ≤ 60% or veno-arterial PCO2 gap ≥ 5 mmHg);\n- Patient affiliated to social security plan."}
Exclusion criteria
- {"criterion_text":"- Myocardial sideration after cardiac arrest of non-cardiac etiology;\n- Person deprived of liberty for judicial or administrative decision\n- Minor (not emancipated)\n- Immediate or anticipated (within 6 hours) indication of ECLS;\n- Adult subject to a legal protection measure (such as guardianship, conservatorship)\n- Use of VA-ECMO or IMPELLA or LVAD\n- Chronic renal failure requiring hemodialysis;\n- Cardiotoxic poisoning\n- Septic cardiomyopathy\n- Previous levosimendan administration within 15 days\n- Cardiac arrest with non-shockable rhythm\n- No flow time higher > 3 minutes\n- Cardiac arrest with unknown no flow duration\n- Total duration of cardiac arrest (no flow plus low flow) > 45 minutes\n- Cerebral deficit with fixed dilated pupils\n- Patient moribund on the day of enrollment\n- Irreversible neurological pathology\n- Known hypersensitivity to levosimendan or placebo, or one of its excipients;\n- Pregnant woman, birthing or breastfeeding mother"}
Endpoints
Primary endpoints
- {"endpoint_text":"- All-cause mortality and/or ECLS and/or dialysis at day 30 following randomization.","definition_or_measurement_approach":"Composite endpoint assessed at day 30 following randomization: occurrence of all-cause mortality and/or requirement for ExtraCorporeal Life Support (ECLS) and/or dialysis."}
Secondary endpoints
- {"endpoint_text":"- Prioritized composite endpoint at days 90 with the following priority order: 1/ time to death, 2/ escalation to permanent left ventricular assist device or cardiac transplantation, 3/ dialysis, 4/ ECLS requirement, 5/ number of cardiovascular events (stroke, recurrent myocardial infarction, urgent coronary revascularization, re-hospitalization for heart failure).\n- Major adverse cardiovascular events: death, ECLS requirement, dialysis, cardiac transplantation, escalation to permanent left ventricular assist device, major cardiovascular events (stroke, recurrent myocardial infarction, urgent coronary revascularization, re-hospitalization for heart failure) on days 90\n- Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis on day 90;\n- Number of dobutamine free days between randomization and D30\n- Number of vasopressors free days between randomization and D30;\n- Number of ventilatory free days between randomization and D30\n- Number of renal replacement free days between randomization and D 90\n- Lactate clearance from randomization to D7\n- Duration of ICU stay and hospitalization\n- Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis on days 7, 60, and 180 days and 12 months following randomization\n- Number of renal replacement free days between randomization and D 30, 60, 180 and at 12 months\n- Major adverse cardiovascular events: death, ECLS requirement, dialysis, cardiac transplantation, escalation to permanent left ventricular assist device, major cardiovascular events (stroke, recurrent myocardial infarction, urgent coronary revascularization, re-hospitalization for heart failure) on days 180 and at 12 months;\n- Occurrence of arrhythmias requiring therapy with anti-arrhythmic drugs or electric cardioversion (including atrial fibrillation, ventricular tachycardia, ventricular fibrillation, torsade de pointe) from randomization to ICU or CCU discharge.\n- Changes in biomarkers between randomization and ICU/CCU discharge\n- For objectives B2 and B3 the primary outcome will be considered","definition_or_measurement_approach":"Secondary endpoints are measured at specified timepoints (days 7, 30, 60, 90, 180 and 12 months) as indicated per endpoint text; includes prioritized composite at day 90 (priority order specified), counts of free-days (dobutamine, vasopressors, ventilatory, renal replacement) between randomization and specified days, lactate clearance to Day 7, duration of ICU/hospital stay, major adverse cardiovascular events at multiple timepoints, arrhythmia occurrence from randomization to ICU/CCU discharge, and changes in biomarkers between randomization and ICU/CCU discharge. For objectives B2 and B3 the primary outcome will be used."}
Recruitment
- Planned Sample Size
- 610
- Recruitment Window Months
- 48
- Consent Approach
- Informed consent is obtained from adult participants (study includes adults ≥18 years). Multiple subject information and informed consent forms are listed (L1_SIS and ICF Adulte; L1_SIS and ICF famille_personne de confiance; L1_SIS and ICF_patient decede; L1_SIS and ICF poursuite Adulte; L1_SIS and ICF_poursuite_famille_personne de confiance; L1_ICF_Attestation inclusion SUVI), indicating procedures for consent from the adult subject and for consent/communication with family or a person of trust; an attestation form for inclusion (SUVI) is also provided. No remote/digital consent methods or available languages are specified in the record. Minors are excluded, and adults under legal protection are excluded.
Geography
- Total Number Of Sites
- 29
- Total Number Of Participants
- 610
France
- Earliest CTIS Part Ii Submission Date
- 16-07-2024
- Latest Decision Or Authorization Date
- 01-08-2024
- Processing Time Days
- 16
- Number Of Sites
- 29
- Number Of Participants
- 610
Sites
- Site Name
- Centre Hospitalier Universitaire Grenoble Alpes
- Department Name
- Médecine intensive réanimation
- Principal Investigator Name
- Joanna BOUGNAUD
- Principal Investigator Email
- JBougnaud1@chu-grenoble.fr
- Contact Person Name
- Joanna BOUGNAUD
- Contact Person Email
- JBougnaud1@chu-grenoble.fr
- Site Name
- Centre Hospitalier Universitaire De Montpellier
- Department Name
- cardiologie
- Principal Investigator Name
- François ROUBILLE
- Principal Investigator Email
- f-roubille@chu-montpellier.fr
- Contact Person Name
- François ROUBILLE
- Contact Person Email
- f-roubille@chu-montpellier.fr
- Site Name
- CHU Besancon
- Department Name
- Réanimation Médicale
- Principal Investigator Name
- Hadrien WINISZEWSKI
- Principal Investigator Email
- hwiniszewski@chu-besancon.fr
- Contact Person Name
- Hadrien WINISZEWSKI
- Contact Person Email
- hwiniszewski@chu-besancon.fr
- Site Name
- CHRU De Nancy
- Department Name
- médecine intensive - réanimation
- Principal Investigator Name
- Bruno LEVY
- Principal Investigator Email
- b.levy@chru-nancy.fr
- Contact Person Name
- Bruno LEVY
- Contact Person Email
- b.levy@chru-nancy.fr
- Site Name
- Centre Hospitalier Universitaire De Nimes
- Department Name
- cardiologie
- Principal Investigator Name
- Benoît LATTUCA
- Principal Investigator Email
- benoit.lattuca@gmail.com
- Contact Person Name
- Benoît LATTUCA
- Contact Person Email
- benoit.lattuca@gmail.com
- Site Name
- Centre Hospitalier Regional De Marseille
- Department Name
- Unité de soins intensifs de cardiologie
- Principal Investigator Name
- Florent ARREGLE
- Principal Investigator Email
- Florent.ARREGLE@ap-hm.fr
- Contact Person Name
- Florent ARREGLE
- Contact Person Email
- Florent.ARREGLE@ap-hm.fr
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- Département de cardiologie et maladies vasculaires
- Principal Investigator Name
- Abdelkader BAKHTI
- Principal Investigator Email
- Abdelkader.BAKHTI@chu-rennes.fr
- Contact Person Name
- Abdelkader BAKHTI
- Contact Person Email
- Abdelkader.BAKHTI@chu-rennes.fr
- Site Name
- Les Hopitaux Universitaires De Strasbourg
- Department Name
- Réanimation médicale
- Principal Investigator Name
- Ferhat MEZIANI
- Principal Investigator Email
- ferhat.meziani@chru-strasbourg.fr
- Contact Person Name
- Ferhat MEZIANI
- Contact Person Email
- ferhat.meziani@chru-strasbourg.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Unité de Soins Intensifs de Cardiologie
- Principal Investigator Name
- Clément DELMAS
- Principal Investigator Email
- delmas.clement@chu-toulouse.fr
- Contact Person Name
- Clément DELMAS
- Contact Person Email
- delmas.clement@chu-toulouse.fr
- Site Name
- Centre Hospitalier Universitaire De Nantes
- Department Name
- Unité de Soins intensifs de Cardiologie – Service de Cardiologie Interventionnelle
- Principal Investigator Name
- Julien PLESSIS
- Principal Investigator Email
- Julien.PLESSIS@chu-nantes.fr
- Contact Person Name
- Julien PLESSIS
- Contact Person Email
- Julien.PLESSIS@chu-nantes.fr
- Site Name
- Centre Hospital Region Metz Thionville
- Department Name
- Réanimation polyvalente
- Principal Investigator Name
- Guillaume LOUIS
- Principal Investigator Email
- guillaume.louis@chr-metz-thionville.fr
- Contact Person Name
- Guillaume LOUIS
- Contact Person Email
- guillaume.louis@chr-metz-thionville.fr
- Site Name
- Centre Hospitalier Universitaire De Bordeaux
- Department Name
- Soins Intensifs Cardiologiques – Plateau de Cardiologie Interventionnelle
- Principal Investigator Name
- Edouard GERBAUD
- Principal Investigator Email
- edouard.gerbaud@chu-bordeaux.fr
- Contact Person Name
- Edouard GERBAUD
- Contact Person Email
- edouard.gerbaud@chu-bordeaux.fr
- Site Name
- Centre Hospitalier Universitaire Rouen
- Department Name
- Unité de réanimation de chirurgie cardiaque
- Principal Investigator Name
- Emmanuel BESNIER
- Principal Investigator Email
- Emmanuel.Besnier@chu-rouen.fr
- Contact Person Name
- Emmanuel BESNIER
- Contact Person Email
- Emmanuel.Besnier@chu-rouen.fr
- Site Name
- Centre Hospitalier Universitaire De Lille
- Department Name
- Service Urgences et Soins Intensifs de Cardiologie
- Principal Investigator Name
- Gilles LEMESLE
- Principal Investigator Email
- gilles.lemesle@chru-lille.fr
- Contact Person Name
- Gilles LEMESLE
- Contact Person Email
- gilles.lemesle@chru-lille.fr
- Site Name
- Centre Hospitalier Universitaire De Bordeaux
- Department Name
- Département d’anesthésie-réanimation
- Principal Investigator Name
- Alexandre OUATTARA
- Principal Investigator Email
- alexandre.ouattara@chu-bordeaux.fr
- Contact Person Name
- Alexandre OUATTARA
- Contact Person Email
- alexandre.ouattara@chu-bordeaux.fr
- Site Name
- University Hospital Of Clermont-Ferrand
- Department Name
- cardiologie et médecine vasculaire
- Principal Investigator Name
- Nicolas COMBARET
- Principal Investigator Email
- n_combaret@chu-clermontferrand.fr
- Contact Person Name
- Nicolas COMBARET
- Contact Person Email
- n_combaret@chu-clermontferrand.fr
- Site Name
- Centre Hospitalier Regional De Marseille
- Department Name
- Unité des soins intensive -Cardiologie
- Principal Investigator Name
- Laurent BONELLO
- Principal Investigator Email
- Laurent.BONELLO@ap-hm.fr
- Contact Person Name
- Laurent BONELLO
- Contact Person Email
- Laurent.BONELLO@ap-hm.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Médecine intensive et réanimation
- Principal Investigator Name
- Alain COMBES
- Principal Investigator Email
- alain.combes@aphp.fr
- Contact Person Name
- Alain COMBES
- Contact Person Email
- alain.combes@aphp.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Plateau urgence et soins critiques cardiologiques
- Principal Investigator Name
- Bertrand SCHEPPLER
- Principal Investigator Email
- bertrand.scheppler@univ-lyon1.fr
- Contact Person Name
- Bertrand SCHEPPLER
- Contact Person Email
- bertrand.scheppler@univ-lyon1.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- médecine intensive réanimation
- Principal Investigator Name
- Armand MEKONTSO DESSAP
- Principal Investigator Email
- armand.dessap@aphp.fr
- Contact Person Name
- Armand MEKONTSO DESSAP
- Contact Person Email
- armand.dessap@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service de Cardiologie – Unité de Soins Intensifs de Cardiologie
- Principal Investigator Name
- David AOUATE
- Principal Investigator Email
- davidrobin.aouate@aphp.fr
- Contact Person Name
- David AOUATE
- Contact Person Email
- davidrobin.aouate@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Caen Normandie
- Department Name
- Cardiologie
- Principal Investigator Name
- Katrien BLANCHART
- Principal Investigator Email
- blanchart-k@chu-caen.fr
- Contact Person Name
- Katrien BLANCHART
- Contact Person Email
- blanchart-k@chu-caen.fr
- Site Name
- Centre Hospitalier Universitaire Grenoble Alpes
- Department Name
- Cardiologie
- Principal Investigator Name
- Nicolas PILIERO
- Principal Investigator Email
- npiliero@chu-grenoble.fr
- Contact Person Name
- Nicolas PILIERO
- Contact Person Email
- npiliero@chu-grenoble.fr
- Site Name
- Centre Hospitalier Universitaire De Dijon
- Department Name
- Médecine Intensive Réanimation
- Principal Investigator Name
- Jean Pierre QUENOT
- Principal Investigator Email
- jean-pierre.quenot@chu-dijon.fr
- Contact Person Name
- Jean Pierre QUENOT
- Contact Person Email
- jean-pierre.quenot@chu-dijon.fr
- Site Name
- Centre Hospitalier D Avignon
- Department Name
- Cardiologie
- Principal Investigator Name
- Stéphane ANDRIEU
- Principal Investigator Email
- SAndrieu@Ch-Avignon.fr
- Contact Person Name
- Stéphane ANDRIEU
- Contact Person Email
- SAndrieu@Ch-Avignon.fr
- Site Name
- Centre Hospitalier Universitaire De Montpellier
- Department Name
- Département d’Anesthésie-Réanimation
- Principal Investigator Name
- Philippe GAUDARD
- Principal Investigator Email
- p-gaudard@chu-montpellier.fr
- Contact Person Name
- Philippe GAUDARD
- Contact Person Email
- p-gaudard@chu-montpellier.fr
- Site Name
- Centre Hospitalier Universitaire De Dijon
- Department Name
- Département d’anesthésie-réanimation
- Principal Investigator Name
- Pierre-Grégoire GUINOT
- Principal Investigator Email
- pierregregoire.guinot@chu-dijon.fr
- Contact Person Name
- Pierre-Grégoire GUINOT
- Contact Person Email
- pierregregoire.guinot@chu-dijon.fr
- Site Name
- Les Hopitaux Universitaires De Strasbourg
- Department Name
- Cardiologie -USIC
- Principal Investigator Name
- Olivier MOREL
- Principal Investigator Email
- olivier.morel@chru-strasbourg.fr
- Contact Person Name
- Olivier MOREL
- Contact Person Email
- olivier.morel@chru-strasbourg.fr
- Site Name
- Centre Hospitalier Et Universitaire De Limoges
- Department Name
- Réanimation polyvalente
- Principal Investigator Name
- Philippe VIGNON
- Principal Investigator Email
- philippe.vignon@unilim.fr
- Contact Person Name
- Philippe VIGNON
- Contact Person Email
- philippe.vignon@unilim.fr
Sponsor
Primary sponsor
- Full Name
- CHRU De Nancy
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- France
Investigational products
- Investigational Product Name
- ZIMINO 2,5 mg/ml, solution à diluer pour perfusion
- Active Substance
- LEVOSIMENDAN
- Modality
- Small molecule
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- Authorised
- Maximum Dose
- 288 µg/Kg (max daily amount as listed)
- Investigational Product Name
- CERNEVIT, poudre pour solution injectable ou pour perfusion
- Active Substance
- RETINOL PALMITATE; ASCORBIC ACID; BIOTIN; COLECALCIFEROL; CYANOCOBALAMIN; DEXPANTHENOL; FOLIC ACID; NICOTINAMIDE; PYRIDOXINE HYDROCHLORIDE; DL-ALPHA-TOCOPHEROL; COCARBOXYLASE TETRAHYDRATE
- Modality
- Small molecule|Peptide/protein/enzyme
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- Authorised
- Maximum Dose
- 288 µg/Kg (max daily amount as listed)
- Investigational Product Name
- SOLUVIT, lyophilisat pour usage parentéral
- Active Substance
- PANTOTHENATE SODIUM; RIBOFLAVIN SODIUM PHOSPHATE; BIOTIN; CYANOCOBALAMIN; FOLIC ACID; NICOTINAMIDE; SODIUM ASCORBATE; THIAMINE NITRATE; PYRIDOXINE HYDROCHLORIDE
- Modality
- Small molecule
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- Authorised
- Maximum Dose
- 288 µg/Kg (max daily amount as listed)
- Combination Treatment
- Yes
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