Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion

NCT04166331 | Completed Phase 3 DMC

• 1 other identifier: 87RI18_0012 (ADAPT)
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 21

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

Keywords

sepsis; Cardiomyopathies; Hypoperfusion; Left Ventricular Systolic Dysfunction

Outcome Measures

Primary Outcomes (1)

• Sequential Organ Failure Assessment (SOFA) score evolution

  Evolution of a modified Sequential (Sepsis-Related) Organ Failure Assessment (SOFA) score (no gradation of the neurologic system) between baseline (before randomization) and Day 1, Day 2 and Day 3 after randomization. Min value =0. Max value =20 . The highest score means the worst situation

  Day 0 to Day 3

Secondary Outcomes (33)

• 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

Study Arms (2)

Control

PLACEBO COMPARATOR

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

Drug: Placebos

Experimental

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

Drug: Dobutamine

Interventions

Placebos 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.

Control

Dobutamine 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.

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years hospitalized in ICU
• \> Septic shock (Sepsis-3 definition):
• Clinically suspected or documented acute infection
• Responsible for organ dysfunction(s): change in SOFA ≥ 2 points
• 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)
• Requiring vasopressor support (Norepinephrine) to maintain steady mean arterial pressure ≥ 65 mmHg
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Limoges: lead
• Centre d'Investigation Clinique 1415: collaborator

Study Sites (21)

CHU Orléans - service de Réanimation

Orléans, Orleans, 47067, France

Location

CHU Strasbourg - service de Réanimation

Strasbourg, Strasbourg, 67000, France

Location

CHU Tours - Service de Réanimation

Tours, Tours, 37044, France

Location

Angouleme Hospital

Angoulême, 16959, France

Location

Argenteuil Hospital

Argenteuil, 95107, France

Location

CH de Bethune

Béthune, France

Location

University Hospital

Brest, 29200, France

Location

CH de Brive

Brive-la-Gaillarde, 19100, France

Location

CH de Cannes

Cannes, France

Location

Aphp - Henri Mondor

Créteil, 94010, France

Location

Dijon university hospital

Dijon, 21033, France

Location

CH d'Haguenau

Haguenau, 67500, France

Location

Le Mans Hospital

Le Mans, 72000, France

Location

Lille University Hospital

Lille, 59045, France

Location

Limoges University Hospital

Limoges, 87042, France

Location

HCL

Lyon, France

Location

Montpellier University Hospital

Montpellier, 34295, France

Location

Nice University Hospital

Nice, 06202, France

Location

Aphp - Ambroise Paré

Paris, 75010, France

Location

Poitiers University Hospital

Poitiers, 86000, France

Location

CH de Toulon

Toulon, 83000, France

Location

Related Publications (1)

• 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.

  PMID: 40588393 DERIVED

MeSH Terms

Conditions

Sepsis; Cardiomyopathies; Ventricular Dysfunction, Left

Interventions

Dobutamine

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction

Intervention Hierarchy (Ancestors)

Catecholamines; Amines; Organic Chemicals; Phenethylamines; Ethylamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• VIGNON Philippe, MD

  University Hospital, Limoges

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: November 18, 2019
• Study Start: September 20, 2020
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (21)