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Completed

NCT Number: NCT04166331

Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion

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.

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Key information

Conditions

Sepsis Cardiomyopathies Cardiovascular Diseases Heart Diseases Hypoperfusion Infections Inflammation Left Ventricular Systolic Dysfunction Pathologic Processes Pathological Conditions, Signs and Symptoms Systemic Inflammatory Response Syndrome Ventricular Dysfunction Ventricular Dysfunction, Left

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CHU Orléans - service de Réanimation, Orléans, Orleans, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

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.

Treatment and study plan

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.

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.

Primary outcomes

  1. Sequential Organ Failure Assessment (SOFA) score evolution

    Time frame: Day 0 to Day 3

    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

Secondary outcomes

  1. Circulating lactate level measurement

    Time frame: Hour 0, Hour 6, Day 1, Day 2 and Day 3

    Biological indices of tissue dysoxia at baseline, hour 6, Day1, Day 2 and Day 3 after initiating Dobutamine / placebo

  2. Central venous oxygen saturation (ScvO2) measurement

    Time frame: Hour 0, Hour 6, Day 1, Day 2 and Day 3

    Biological indices of tissue dysoxia at baseline, hour 6, Day1, Day 2 and Day 3 after initiating Dobutamine / placebo

  3. Open-labelled Dobutamine dayly maximal dose used as rescue therapy

    Time frame: through study completion, an average 90 days

    Requirement of organ function supports during ICU stay. Maximal dose in mcg/kg/min of open-labelled Dobutamine used as rescue therapy

  4. Open-labelled Dobutamine duration used as rescue therapy

    Time frame: through study completion, an average of 90 days

    Requirement of organ function supports during ICU stay. Duration in days of open-labelled Dobutamine used as rescue therapy

  5. Vasopressor support duration

    Time frame: through study completion, an average of 90 days

    Requirement of organ function supports during ICU stay. Duration in days of vasopressor support

  6. Vasopressor support dayly maximal dose

    Time frame: through study completion, an average of 90 days

    Requirement of organ function supports during ICU stay. Maximal dose in mg/h by day of vasopressor support

  7. Invasive mechanical ventilation duration

    Time frame: through study completion, an average of 90 days

    Requirement of organ function supports during ICU stay. Duration of invasive mechanical ventilation

  8. Renal replacement therapy number

    Time frame: through study completion, an average of 90 days

    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)

  9. Renal replacement therapy duration

    Time frame: through study completion, an average of 90 days

    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)

  10. Arterial pressure measurement

    Time frame: Hour 0, Hour 6, Day 1, Day 2 and Day 3

    Systolic, diastolic and mean arterial blood pressure (in mmHg) at Baseline, h6, Day 1, Day 2 and Day3after initiating Dobutamine / placebo

  11. heart rate measurement

    Time frame: Hour 0, Hour 6, Day 1, Day 2 and Day 3

    Heart rate measurement in bpm at Baseline, Hour 6, Day 1, Day 2 and Day3 after initiating Dobutamine / placebo

  12. Central venous pressure measurement

    Time frame: Hour 0, Hour 6, Day 1, Day 2 and Day 3

    Central venous pressure in cm H2O at Baseline, Hour 6, Day 1, Day 2 and Day3 after initiating Dobutamine / placebo

  13. Cardiac index measurement

    Time frame: Hour 0, Hour 6, Day 1, Day 2 and Day 3

    Cardiac index measurement in L/min/m2 at Baseline, Hour 6, Day 1, Day 2 and Day3 after initiating Dobutamine / placebo

  14. Stroke volume measurement

    Time frame: Hour 0, Hour 6, Day 1, Day 2 and Day 3

    Stroke volume measurement in mL status at Baseline, Hour 6, Day 1, Day 2 and Day3 after initiating Dobutamine / placebo

  15. Hypotension measurement

    Time frame: Hour 0, Hour 6, Day 1, Day 2 and Day 3

    Severe cardiovascular adverse events from inform consent to ICU discharge : Hypotension related to worsened vasoplegia

  16. Supraventricular arrhythmias measurement

    Time frame: through study completion, an average of 90 days

    Severe cardiovascular adverse events from inform consent to ICU discharge. Supraventricular arrhythmias with ventricular rate > 140 bpm

  17. Ventricular arrhythmias measurement

    Time frame: through study completion, an average of 90 days

    Severe cardiovascular adverse events from inform consent to ICU discharge. Ventricular arrhythmias

  18. Occurence of Acute coronary syndrome

    Time frame: through study completion, an average of 90 days

    Severe cardiovascular adverse events from inform consent to ICU discharge. Acute coronary syndrome

  19. Occurence of Stroke

    Time frame: through study completion, an average of 90 days

    Severe cardiovascular adverse events during ICU stay. Stroke

  20. Mortality

    Time frame: Day 90

    Number of death

  21. Mortality causes

    Time frame: Day 90

    Cause of death

  22. Organ function free supports

    Time frame: Day 90

    Number of days free from vasopressor support, invasive mechanical ventilation, renal replacement therapy from inform consent to ICU discharge

  23. Number of days in ICU and hospital

    Time frame: Day 90

    Length of ICU and hospital stay

  24. echocardiographic assessment of left ventricular systolic function

    Time frame: Day 0 and Day 1

    ejection fraction measurement

  25. Leucocyte subsets level

    Time frame: Hour 6

    Leucocyte subsets level according to the severity of the sepsis-induced LV systolic dysfunction and hemodynamic effects of the study drug administration

  26. Cytokines level

    Time frame: Hour 6

    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.

  27. LV global longitudinal strain measurement

    Time frame: Hour 6, Day 1, Day 2 AND Day 3

    LV segmental deformation longitudinal analysis

  28. RV free wall strain measurement

    Time frame: Hour 6, Day 1, Day 2 AND Day 3

    deformation of right ventricular myocardial tissue / routinely using with echocardiography or post exam analysis

  29. LV volume measurement

    Time frame: Hour 6, Day 1, Day 2 AND Day 3

    Ratio between systolic and diastolic left ventricular volume / routinely using with echocardiography

  30. LV ejection fraction measurement

    Time frame: Hour 6, Day 1, Day 2 AND Day 3

    Cardiac output measurement with echocardiography Doppler (in centers routinely using transpulmonary thermodilution). Quality of left ventricular contraction

  31. RV volume measurement

    Time frame: Hour 6, Day 1, Day 2 AND Day 3

    Ratio between systolic and diastolic right ventricular volume / routinely using with echocardiography

  32. RV ejection fraction measurement

    Time frame: Hour 6, Day 1, Day 2 AND Day 3

    Cardiac output measurement with echocardiography Doppler (in centers routinely using transpulmonary thermodilution). Quality of right ventricular contraction

  33. Transpulmonary thermodilution measurement

    Time frame: Hour 6, Day 1, Day 2 AND Day 3

    In selected centers routinely using continuous monitoring of cardiac output using transpulmonary thermodilution: agreement of cardiac output measurement with echocardiography Doppler.

Sponsors and collaborators

Lead sponsor

University Hospital, Limoges

Other

Collaborators

  • Centre d'Investigation Clinique 1415

Registry information

Official study title

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

Acronym: ADAPT

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
Nov 18, 2019
Registry last updated
Nov 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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