Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion: a Randomized Controlled Multi-center Trial
Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
Sponsors
Source
University Hospital, Limoges
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
No
Is Fda Regulated Device
No
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.
Overall Status
Not yet recruiting
Start Date
2020-02-01
Completion Date
2022-05-01
Primary Completion Date
2022-02-04
Phase
Phase 3
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Sequential Organ Failure Assessment (SOFA) score evolution |
Day 0 to Day 3 |
Secondary Outcome
Measure |
Time Frame |
|
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 |
Enrollment
270
Conditions
Intervention
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
Control
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
Experimental
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.
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
VIGNON Philippe, MD |
Principal Investigator |
University Hospital, Limoges |
Overall Contact
Location
Facility | |||
|
University Hospital Amiens 80000 France | |||
|
University Hospital Brest 29200 France | |||
|
Aphp - Henri Mondor Créteil 94010 France |
Not yet recruiting |
Last Name: MEKONTSO-DESSAP Armand, MD |
Last Name: MEKONTSO-DESSAP Armand, MD Role: Principal Investigator |
|
Limoges University Hospital Limoges 87042 France |
Not yet recruiting |
Last Name: Philippe Vignon, MD Role: Principal Investigator Last Name: Bruno François, MD Role: Sub-Investigator Last Name: Thomas Daix, MD Role: Sub-Investigator | |
|
CHU de Nancy Nancy 54511 France | |||
|
CHU Orléans - service de Réanimation Orleans 47067 France | |||
|
Aphp - Ambroise Paré Paris 75010 France | |||
|
Hôpital Cochin - service de Réanimation Paris 75014 France | |||
|
CHU Strasbourg - service de Réanimation Strasbourg 67000 France | |||
|
CHU Tours - Service de Réanimation Tours 37044 France |
Location Countries
Country
France
Verification Date
2019-11-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Number Of Arms
2
Intervention Browse
Mesh Term
Dobutamine
Arm Group
Arm Group Label
Control
Arm Group Type
Placebo Comparator
Description
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
Arm Group Label
Experimental
Arm Group Type
Experimental
Description
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
Firstreceived Results Date
N/A
Overall Contact Backup
Acronym
ADAPT
Patient Data
Sharing Ipd
No
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Study First Submitted
October 25, 2019
Study First Submitted Qc
November 15, 2019
Study First Posted
November 18, 2019
Last Update Submitted
November 15, 2019
Last Update Submitted Qc
November 15, 2019
Last Update Posted
November 18, 2019
ClinicalTrials.gov processed this data on December 11, 2019
Conditions
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conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.