Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion

Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion: a Randomized Controlled Multi-center Trial

Patrocinadores

Patrocinador principal: University Hospital, Limoges

Colaborador: Centre d’Investigation Clinique 1415

Fuente University Hospital, Limoges
Resumen breve

Sepsis induces both a systolic and diastolic cardiac dysfunction. The prevalence of this septic cardiomyopathy ranges between 30 and 60% according to the timing of assessment and definition used. Although the prognostic role of septic cardiomyopathy remains debated, sepsis-induced left ventricular (LV) systolic dysfunction may be severe and associated with tissue hypoperfusion, while it appears to fully recover in survivors. Accordingly, optimization of therapeutic management of septic cardiomyopathy may contribute to improve tissue hypoperfusion in increasing oxygen delivery, and to reduce related organ dysfunctions in septic shock patients.

Echocardiography is currently the recommended first-line modality to assess patients with acute circulatory failure.

Current Surviving Sepsis Campaign strongly recommends Norepinephrine as the first-choice vasopressor in fluid-filled patients with septic shock. In contrast, the use of Dobutamine is only suggested (weak recommendation, low quality of evidence) in patients with persistent tissue hypoperfusion despite adequate fluid resuscitation and vasopressor support. Levosimendan, an alternative inodilator, has failed preventing acute organ dysfunction in septic patients and has induced more supraventricular tachyarrhythmias than in the control group. Data supporting Dobutamine in this setting are scarce and primarily physiologic and based on monitored effects of this drug on hemodynamics and indices of tissue perfusion.

No randomized controlled trials have yet compared the effects of Dobutamine versus placebo on clinical outcomes. In open-labelled, small sample trials, the ability of septic patients to increase their oxygen delivery during Dobutamine administration appears to be associated with lower mortality.

The tested hypothesis in the ADAPT trial is that Dobutamine will reduce tissue hypoperfusion and associated organ dysfunctions in patients with septic shock and associated septic cardiomyopathy. In doing so, it may participate in improving clinical outcomes.

Estado general Recruiting
Fecha de inicio June 26, 2020
Fecha de Terminación September 26, 2022
Fecha de finalización primaria June 30, 2022
Fase Phase 3
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Sequential Organ Failure Assessment (SOFA) score evolution Day 0 to Day 3
Resultado secundario
Medida Periodo de tiempo
Circulating lactate level measurement Hour 0, Hour 6, Day 1, Day 2 and Day 3
Central venous oxygen saturation (ScvO2) measurement Hour 0, Hour 6, Day 1, Day 2 and Day 3
Open-labelled Dobutamine dayly maximal dose used as rescue therapy through study completion, an average 90 days
Open-labelled Dobutamine duration used as rescue therapy through study completion, an average of 90 days
Vasopressor support duration through study completion, an average of 90 days
Vasopressor support dayly maximal dose through study completion, an average of 90 days
Invasive mechanical ventilation duration through study completion, an average of 90 days
Renal replacement therapy number through study completion, an average of 90 days
Renal replacement therapy duration through study completion, an average of 90 days
Arterial pressure measurement Hour 0, Hour 6, Day 1, Day 2 and Day 3
heart rate measurement Hour 0, Hour 6, Day 1, Day 2 and Day 3
Central venous pressure measurement Hour 0, Hour 6, Day 1, Day 2 and Day 3
Cardiac index measurement Hour 0, Hour 6, Day 1, Day 2 and Day 3
Stroke volume measurement Hour 0, Hour 6, Day 1, Day 2 and Day 3
Hypotension measurement Hour 0, Hour 6, Day 1, Day 2 and Day 3
Supraventricular arrhythmias measurement through study completion, an average of 90 days
Ventricular arrhythmias measurement through study completion, an average of 90 days
Occurence of Acute coronary syndrome through study completion, an average of 90 days
Occurence of Stroke through study completion, an average of 90 days
Mortality Day 90
Mortality causes Day 90
Organ function free supports Day 90
Number of days in ICU and hospital Day 90
echocardiographic assessment of left ventricular systolic function Day 0 and Day 1
Leucocyte subsets level Hour 6
Cytokines level Hour 6
LV global longitudinal strain measurement Hour 6, Day 1, Day 2 AND Day 3
RV free wall strain measurement Hour 6, Day 1, Day 2 AND Day 3
LV volume measurement Hour 6, Day 1, Day 2 AND Day 3
LV ejection fraction measurement Hour 6, Day 1, Day 2 AND Day 3
RV volume measurement Hour 6, Day 1, Day 2 AND Day 3
RV ejection fraction measurement Hour 6, Day 1, Day 2 AND Day 3
Transpulmonary thermodilution measurement Hour 6, Day 1, Day 2 AND Day 3
Inscripción 270
Condición
Intervención

Tipo de intervención: Drug

Nombre de intervención: Placebos

Descripción: Placebo will initially be started at a dose of 2.5 µg/kg/min and subsequently titrated using incremental steps (predefined durations) of 2.5 µg/kg/min, up to a maximal dose of 10 µg/kg/min. Dose adaptation will be left at the discretion of attending physician.

Etiqueta de grupo de brazo: Control

Tipo de intervención: Drug

Nombre de intervención: Dobutamine

Descripción: Dobutamine will initially be started at a dose of 2.5 µg/kg/min and subsequently titrated using incremental steps (predefined durations) of 2.5 µg/kg/min, up to a maximal dose of 10 µg/kg/min. Dose adaptation will be left at the discretion of attending physician.

Etiqueta de grupo de brazo: Experimental

Elegibilidad

Criterios:

Inclusion Criteria:

- Age > 18 years hospitalized in ICU

- > Septic shock (Sepsis-3 definition):

1. Clinically suspected or documented acute infection

2. Responsible for organ dysfunction(s): change in SOFA ≥ 2 points

3. With persisting hypotension (systolic and/or mean arterial pressure < 90 / < 65 mmHg) despite adequate fluid resuscitation (≥ 30 mL/kg, unless presence of pulmonary venous congestion)

4. Requiring vasopressor support (Norepinephrine) to maintain steady mean arterial pressure ≥ 65 mmHg

5. And lactate > 2 mmol/L

- Septic cardiomyopathy: echocardiographically measured LV ejection fraction (EF) ≤ 40% and LV outflow tract velocity-time integral < 14 cm

- Informed consent

Exclusion Criteria:

- Pregnancy or breast feeding

- Hypersensitivity to Dobutamine, 5% Dextrose, or to the excipients

- Ventricular rate > 130 bpm (sinus rhythm or not)

- Severe ventricular arrhythmia

- Obstructive cardiomyopathy with pressure gradient at rest ≥ 50 mmHg unrelated to uncorrected hypovolemia

- Severe aortic stenosis: mean gradient > 40 mmHg, peak aortic jet velocity > 4 m/s, aortic valve area < 1 cm² (aortic valve area index < 0.6 cm²/m²)

- Acute coronary syndrome

- Decision to limit care or moribund status (life expectancy < 24 h)

- Absence of affiliation to Social Security

- Subjects under juridical protection.

Género: All

Edad mínima: 18 Years

Edad máxima: N/A

Voluntarios Saludables: No

Oficial general
Apellido Papel Afiliación
VIGNON Philippe, MD Principal Investigator University Hospital, Limoges
Contacto general

Apellido: VIGNON Philippe, MD

Teléfono: 555054040

Teléfono Ext.: +33

Email: [email protected]

Ubicación
Instalaciones: Estado: Contacto: Investigador:
University Hospital | Amiens, 80000, France Not yet recruiting Michel SLAMA, MD +33322455854 [email protected] Michel SLAMA, MD Principal Investigator Julien MAIZEL, MD Sub-Investigator Loay KONTAR, MD Sub-Investigator
Angouleme Hospital | Angoulême, 16959, France Not yet recruiting Stéphane ROULEAU, MD 545244157 +33 [email protected] Stéphane ROULEAU, MD Principal Investigator
Argenteuil Hospital | Argenteuil, 95107, France Not yet recruiting Gaëtan PLANTEFEVE, MD 134232550 [email protected] Gaëtan PLANTEFEVE, MD Principal Investigator
University Hospital | Brest, 29200, France Recruiting Gwanaël PRAT, MD +33298347181 [email protected] Gwanaël PRAT, MD Principal Investigator Pierre BAILLY, MD Sub-Investigator
Aphp - Henri Mondor | Créteil, 94010, France Not yet recruiting MEKONTSO-DESSAP Armand, MD MEKONTSO-DESSAP Armand, MD Principal Investigator
Dijon university hospital | Dijon, 21033, France Not yet recruiting Jean-Pierre QUENOT, MD 380295921 +33 [email protected] Jean-Pierre QUENOT, MD Principal Investigator
Limoges University Hospital | Limoges, 87042, France Recruiting Philippe Vignon, MD +33555054040 [email protected] Philippe Vignon, MD Principal Investigator Bruno François, MD Sub-Investigator Thomas Daix, MD Sub-Investigator
CHU de Nancy | Nancy, 54511, France Not yet recruiting Bruno LEVY, MD 383154084 +33 [email protected] Bruno LEVY, MD Principal Investigator Thomas AUCHER, MD Sub-Investigator Caroline FRITZ, MD Sub-Investigator Antoine KIMMOUN, MD Sub-Investigator Simon LEMOINE, MD Sub-Investigator Mathieu MATTEI, MD Sub-Investigator Pierre PEREZ, MD Sub-Investigator Carine THIVILLIER, MD Sub-Investigator Christelle SIMONOT, MD Sub-Investigator
CHU Orléans - service de Réanimation | Orleans, 47067, France Not yet recruiting Thierry BOULAIN, MD 02 38 51 44 46 [email protected] Thierry Boulain, MD Principal Investigator Armelle Mathonnet, MD Sub-Investigator Dalila Benzekri-Lefèvre, MD Sub-Investigator Anne Bretagnol, MD Sub-Investigator Isabelle Rugne, MD Sub-Investigator François Barbier, MD Sub-Investigator Grégoire Muller, MD Sub-Investigator Toufik Kamel, MD Sub-Investigator Mai-Anh Nay, MD Sub-Investigator
Aphp - Ambroise Paré | Paris, 75010, France Not yet recruiting Antoine VIEILLARD-BARON, MD +33149095603 [email protected] Antoine VIEILLARD-BARON, MD Principal Investigator Xavier REPESSE, MD Sub-Investigator Cyril CHARRON, MD Sub-Investigator
Hôpital Cochin - service de Réanimation | Paris, 75014, France Not yet recruiting Jean-Paul MIRA, MD Jean-Paul MIRA, MD Sub-Investigator
Poitiers University Hospital | Poitiers, 86000, France Not yet recruiting Florence BOISSIER, MD 549444367 +33 [email protected] Florence BOISSIER, MD Principal Investigator
CHU Strasbourg - service de Réanimation | Strasbourg, 67000, France Not yet recruiting Ferhat MEZIANI, MD 03 69 55 04 34 [email protected] Ferhat Meziani, MD Principal Investigator Christine Kummerlen, MD Sub-Investigator Tarik Khoury, MD Sub-Investigator Xavier Delabranche, MD Sub-Investigator Hassene Rahmani, MD Sub-Investigator Sarah Heenen, MD Sub-Investigator Yannick Rabouel, MD Sub-Investigator Alexandra Boivin, MD Sub-Investigator Raphaël Clere-Jehl, MD Sub-Investigator Alexandra Monnier, MD Sub-Investigator Julie Boisramé-Helms, MD Sub-Investigator
CHU Tours - Service de Réanimation | Tours, 37044, France Not yet recruiting Emmanuelle MERCIER, MD Pierre-François Dequin, MD Sub-Investigator Youenn Jouan, MD Sub-Investigator Antoine Guillon, MD Sub-Investigator Denis Garot, MD Sub-Investigator Emmanuelle Mercier, MD Principal Investigator Stepahn Ehrmann, MD Sub-Investigator Laetitia Bodet-Contentin, MD Sub-Investigator Emmanuelle Rouve, MD Sub-Investigator Julie Mankikian, MD Sub-Investigator Annick Legras, MD Sub-Investigator Charlotte Salmon-Gandonnière, MD Sub-Investigator
Ubicacion Paises

France

Fecha de verificación

July 2020

Fiesta responsable

Tipo: Sponsor

Palabras clave
Tiene acceso ampliado No
Condición Examinar
Número de brazos 2
Grupo de brazo

Etiqueta: Control

Tipo: Placebo Comparator

Descripción: Placebo will initially be started at a dose of 2.5 µg/kg/min and subsequently titrated using incremental steps (predefined durations) of 2.5 µg/kg/min, up to a maximal dose of 10 µg/kg/min

Etiqueta: Experimental

Tipo: Experimental

Descripción: Dobutamine will initially be started at a dose of 2.5 µg/kg/min and subsequently titrated using incremental steps (predefined durations) of 2.5 µg/kg/min, up to a maximal dose of 10 µg/kg/min

Acrónimo ADAPT
Datos del paciente No
Información de diseño del estudio

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Propósito primario: Treatment

Enmascaramiento: Triple (Participant, Care Provider, Investigator)

Fuente: ClinicalTrials.gov