| 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)
|
