Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion (ADAPT)

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

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.

Study Overview

• Status: Completed
• Conditions: Sepsis; Cardiomyopathies; Hypoperfusion; Left Ventricular Systolic Dysfunction
• Intervention / Treatment: Drug: Placebos; Drug: Dobutamine

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angoulême, France, 16959
    • Angouleme Hospital
  • Argenteuil, France, 95107
    • Argenteuil Hospital
  • Brest, France, 29200
    • University Hospital
  • Brive-la-Gaillarde, France, 19100
    • CH de Brive
  • Béthune, France
    • CH de Béthune
  • Cannes, France
    • CH de Cannes
  • Créteil, France, 94010
    • APHP - Henri Mondor
  • Dijon, France, 21033
    • Dijon University Hospital
  • Haguenau, France, 67500
    • CH d'Haguenau
  • Le Mans, France, 72000
    • Le Mans Hospital
  • Lille, France, 59045
    • Lille University Hospital
  • Limoges, France, 87042
    • Limoges University Hospital
  • Lyon, France
    • HCL
  • Montpellier, France, 34295
    • Montpellier University Hospital
  • Nice, France, 06202
    • Nice University Hospital
  • Paris, France, 75010
    • Aphp - Ambroise Paré
  • Poitiers, France, 86000
    • Poitiers University Hospital
  • Toulon, France, 83000
    • CH de Toulon
  • Orleans
    • Orléans, Orleans, France, 47067
      • CHU Orléans - service de Réanimation
  • Strasbourg
    • Strasbourg, Strasbourg, France, 67000
      • CHU Strasbourg - service de Réanimation
  • Tours
    • Tours, Tours, France, 37044
      • CHU Tours - Service de Réanimation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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	Drug: 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.
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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating lactate level measurement	Biological indices of tissue dysoxia at baseline, hour 6, Day1, Day 2 and Day 3 after initiating Dobutamine / placebo	Hour 0, Hour 6, Day 1, Day 2 and Day 3
Central venous oxygen saturation (ScvO2) measurement	Biological indices of tissue dysoxia at baseline, hour 6, Day1, Day 2 and Day 3 after initiating Dobutamine / placebo	Hour 0, Hour 6, Day 1, Day 2 and Day 3
Open-labelled Dobutamine dayly maximal dose used as rescue therapy	Requirement of organ function supports during ICU stay. Maximal dose in mcg/kg/min of open-labelled Dobutamine used as rescue therapy	through study completion, an average 90 days
Open-labelled Dobutamine duration used as rescue therapy	Requirement of organ function supports during ICU stay. Duration in days of open-labelled Dobutamine used as rescue therapy	through study completion, an average of 90 days
Vasopressor support duration	Requirement of organ function supports during ICU stay. Duration in days of vasopressor support	through study completion, an average of 90 days
Vasopressor support dayly maximal dose	Requirement of organ function supports during ICU stay. Maximal dose in mg/h by day of vasopressor support	through study completion, an average of 90 days
Invasive mechanical ventilation duration	Requirement of organ function supports during ICU stay. Duration of invasive mechanical ventilation	through study completion, an average of 90 days
Renal replacement therapy number	Requirement of organ function supports during ICU stay. Number of session of renal replacement therapy (excluding hemodialysis patient for chronic renal failure at the time of randomization)	through study completion, an average of 90 days
Renal replacement therapy duration	Requirement of organ function supports during ICU stay. Duration of renal replacement therapy (excluding hemodialysis patient for chronic renal failure at the time of randomization)	through study completion, an average of 90 days
Arterial pressure measurement	Systolic, diastolic and mean arterial blood pressure (in mmHg) at Baseline, h6, Day 1, Day 2 and Day3after initiating Dobutamine / placebo	Hour 0, Hour 6, Day 1, Day 2 and Day 3
heart rate measurement	Heart rate measurement in bpm at Baseline, Hour 6, Day 1, Day 2 and Day3 after initiating Dobutamine / placebo	Hour 0, Hour 6, Day 1, Day 2 and Day 3
Central venous pressure measurement	Central venous pressure in cm H2O at Baseline, Hour 6, Day 1, Day 2 and Day3 after initiating Dobutamine / placebo	Hour 0, Hour 6, Day 1, Day 2 and Day 3
Cardiac index measurement	Cardiac index measurement in L/min/m2 at Baseline, Hour 6, Day 1, Day 2 and Day3 after initiating Dobutamine / placebo	Hour 0, Hour 6, Day 1, Day 2 and Day 3
Stroke volume measurement	Stroke volume measurement in mL status at Baseline, Hour 6, Day 1, Day 2 and Day3 after initiating Dobutamine / placebo	Hour 0, Hour 6, Day 1, Day 2 and Day 3
Hypotension measurement	Severe cardiovascular adverse events from inform consent to ICU discharge : Hypotension related to worsened vasoplegia	Hour 0, Hour 6, Day 1, Day 2 and Day 3
Supraventricular arrhythmias measurement	Severe cardiovascular adverse events from inform consent to ICU discharge. Supraventricular arrhythmias with ventricular rate > 140 bpm	through study completion, an average of 90 days
Ventricular arrhythmias measurement	Severe cardiovascular adverse events from inform consent to ICU discharge. Ventricular arrhythmias	through study completion, an average of 90 days
Occurence of Acute coronary syndrome	Severe cardiovascular adverse events from inform consent to ICU discharge. Acute coronary syndrome	through study completion, an average of 90 days
Occurence of Stroke	Severe cardiovascular adverse events during ICU stay. Stroke	through study completion, an average of 90 days
Mortality	Number of death	Day 90
Mortality causes	Cause of death	Day 90
Organ function free supports	Number of days free from vasopressor support, invasive mechanical ventilation, renal replacement therapy from inform consent to ICU discharge	Day 90
Number of days in ICU and hospital	Length of ICU and hospital stay	Day 90
echocardiographic assessment of left ventricular systolic function	ejection fraction measurement	Day 0 and Day 1
Leucocyte subsets level	Leucocyte subsets level according to the severity of the sepsis-induced LV systolic dysfunction and hemodynamic effects of the study drug administration	Hour 6
Cytokines level	tumor necrosis factor (TNF) -α, Interferon ɣ, Interleukin-6, 8 and 10 cytokines concentration will be assess according to the severity of the sepsis-induced LV systolic dysfunction and hemodynamic effects of the study drug administration. Result for each cytokine concentration will be given in picograms per milliliter.	Hour 6
LV global longitudinal strain measurement	LV segmental deformation longitudinal analysis	Hour 6, Day 1, Day 2 AND Day 3
RV free wall strain measurement	deformation of right ventricular myocardial tissue / routinely using with echocardiography or post exam analysis	Hour 6, Day 1, Day 2 AND Day 3
LV volume measurement	Ratio between systolic and diastolic left ventricular volume / routinely using with echocardiography	Hour 6, Day 1, Day 2 AND Day 3
LV ejection fraction measurement	Cardiac output measurement with echocardiography Doppler (in centers routinely using transpulmonary thermodilution). Quality of left ventricular contraction	Hour 6, Day 1, Day 2 AND Day 3
RV volume measurement	Ratio between systolic and diastolic right ventricular volume / routinely using with echocardiography	Hour 6, Day 1, Day 2 AND Day 3
RV ejection fraction measurement	Cardiac output measurement with echocardiography Doppler (in centers routinely using transpulmonary thermodilution). Quality of right ventricular contraction	Hour 6, Day 1, Day 2 AND Day 3
Transpulmonary thermodilution measurement	In selected centers routinely using continuous monitoring of cardiac output using transpulmonary thermodilution: agreement of cardiac output measurement with echocardiography Doppler.	Hour 6, Day 1, Day 2 AND Day 3

Collaborators and Investigators

• Sponsor: University Hospital, Limoges
• Collaborators: Centre d'Investigation Clinique 1415
• Investigators: Principal Investigator: VIGNON Philippe, MD, University Hospital, Limoges

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2020
• Primary Completion (Actual): July 1, 2025
• Study Completion (Actual): July 1, 2025

Study Registration Dates

• First Submitted: October 25, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 18, 2019

Study Record Updates

• Last Update Posted (Estimated): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: sepsis; Hypoperfusion; Left Ventricular Systolic Dysfunction; Cardiomyopathies
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Ventricular Dysfunction; Pathological Conditions, Signs and Symptoms; Sepsis; Ventricular Dysfunction, Left; Cardiomyopathies; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Catechols; Phenols; Benzene Derivatives; Phenethylamines; Ethylamines; Catecholamines; Dobutamine
• Other Study ID Numbers: 87RI18_0012 (ADAPT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No