Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion

NCT ID: NCT04166331

Last Updated: 2025-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-20
• Study Completion Date: 2025-07-01

Brief Summary

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.

Conditions

Sepsis; Cardiomyopathies; Hypoperfusion; Left Ventricular Systolic Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Control

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

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

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.

Experimental

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

Group Type: EXPERIMENTAL

Dobutamine

Intervention Type: DRUG

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.

Interventions

Placebos

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.

Intervention Type: DRUG

Dobutamine

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre d'Investigation Clinique 1415

UNKNOWN

Sponsor Role: collaborator

University Hospital, Limoges

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

VIGNON Philippe, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Limoges

Locations

CHU Orléans - service de Réanimation

Orléans, Orleans, France

CHU Strasbourg - service de Réanimation

Strasbourg, Strasbourg, France

CHU Tours - Service de Réanimation

Tours, Tours, France

Angouleme Hospital

Angoulême, , France

Argenteuil Hospital

Argenteuil, , France

CH de Bethune

Béthune, , France

University Hospital

Brest, , France

CH de Brive

Brive-la-Gaillarde, , France

CH de Cannes

Cannes, , France

Aphp - Henri Mondor

Créteil, , France

Dijon university hospital

Dijon, , France

CH d'Haguenau

Haguenau, , France

Le Mans Hospital

Le Mans, , France

Lille University Hospital

Lille, , France

Limoges University Hospital

Limoges, , France

HCL

Lyon, , France

Montpellier University Hospital

Montpellier, , France

Nice University Hospital

Nice, , France

Aphp - Ambroise Paré

Paris, , France

Poitiers University Hospital

Poitiers, , France

CH de Toulon

Toulon, , France

Countries

France

References

Vignon P, Leger J, Evrard B, Goudelin M, Vaidie J, Brit S, Giraudeau B. Adjunctive dobutamine in patients with septic cardiomyopathy and tissue hypoperfusion: a blinded randomised controlled multicentre trial study protocol of the ADAPT-dobutamine trial. BMJ Open. 2025 Jun 30;15(6):e101200. doi: 10.1136/bmjopen-2025-101200.

Reference Type: DERIVED

PMID: 40588393 (View on PubMed)

Other Identifiers

87RI18_0012 (ADAPT)

Identifier Type: -

Identifier Source: org_study_id