Norepinephrine vs Norepinephrine and Dobutamine in Cardiogenic Shock

NCT03340779 | Unknown Phase 3

• 1 other identifier: 2017-001270-41
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiogenic shock is a frequent cause of admission and death in the intensive care unit. Mortality is about 50%. Once the etiologic treatment has been done, for instance coronary revascularization, management of the shock state is the cornerstone of the treatment. Norepinephrine is the first-line vasopressor therapy because of its minor effect on heart rhythm. Morever norepinephrine is a inotrope. In a previous study, we demonstrated that increasing the norepinephrine dose increases cardiac index, cardiac power index, SVO2 and tissue perfusion without acceleration of heart rate. Nevertheless, dobutamine remains the first-line inotropic treatment. Dobutamine has a positive chronotropic effect that might cause higher myocardial oxygen consumption. As a result, combination of vasopressor / inotrope is still controversial. The aim of this study was to compare hemodynamics and metabolics effects of 2 treatments strategies (norepinephrine dose increasing or addition of dobutamine) in patients with cardiogenic shock and optimised blood pressure level (MAP≥65 mmHg) under norepinephrine treatment. The secondary objectives were :

• To evaluate the efficacy of the treatments on micro- and macrocirculation parameters
• To evaluate the tolerance of the treatments
• To evaluate the dose and the admistration's kinetics of the treatments

Conditions

Cardiogenic Shock

Keywords

Norepinephrine; Dobutamine; Shock

Outcome Measures

Primary Outcomes (1)

• Obtention of a optimal cardiac output

  Measure of increase of cardiac index \> 15% (L/min/m²), increase of organ perfusion assessed by : lactate clearance \> 15% (mmoL/L), decrease of mottling (decrease of 2 points of Mottling score), increase of musculaire oxygen saturation measured by NIRS \> 15% (rSo2%), increase of urine output \> 50% (mL/h), increase of SVcO2 \> 15%(%) Evaluation of occurence of side effects : Increase of heart rate \> 15% (bpm) , increase of oxygen consumption evaluated by decrease of ratio mean arterial pressure / heart rate \> 15% (Buffington ratio). The primary endpoint is defined by the presence of 2 efficacy criterias without any side effects.

  Hour 0 (H0), Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5

Secondary Outcomes (11)

• Change in hemodynamic parameters

  Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5

• Occurence of arrythmia

  Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5

• Change in hemodynamic parameters

  Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5

• All-cause mortality

  Day 28

• Change in hemodynamic parameters

  Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5

Study Arms (2)

Norepinephrine alone

EXPERIMENTAL

Administration of norepinephrine with increasing dose

Drug: Norepinephrine

Norepinephrine plus Dobutamine

ACTIVE COMPARATOR

Administration of norepinephrine and dobutamine

Drug: Norepinephrine

Interventions

Norepinephrine DRUG

After obtention of a mean arterial pressure (MAP) of 65 mmHg with infusion of norepinephrine, patients with cardiogenic shock receive for 3 hours either increasing doses of norepinephrine (with a maximal MAP of 85 mmHg) or dobutamine. There is a wash-out phase of 30 minutes (decrease of norepinephrine dose or weaning of dobutamine). The third phase of the study is the administration of the comparator treatment during 3 hours. After the 6.5 hours of the study, the hemodynamic management is up to the physician.

Also known as: Dobutamine

Norepinephrine alone; Norepinephrine plus Dobutamine

Eligibility Criteria

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

You may qualify if:

• Patients with cardiogenic shock (ischemic, rythmic, valvular) defined : by cardiac index (CI) \< 2,2 L/min/m² or CI \< 2,5 L/min/m² under vasopressor/inotropic treatment and organ hypoperfusion signs : mottles, capillary refill time , urine output \< 0,5 mL/kg/hour during at least one hour ou renal replacement therapy, consciouness impairment, pulmonary oedema, hyperlactatemia (\> 2 mmoL/L)
• Mean arterial pressure \> 65 mmHg under norepinephrine treatment
• Patients with social coverage

You may not qualify if:

• \< 18 years old
• Pregnancy
• Poisonings with cardiotoxicants
• Patient with intra-aortic ballon pump, extracorporeal life support
• Patient under guardianship

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (1)

CHU Nancy-Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

MeSH Terms

Conditions

Shock, Cardiogenic; Shock

Interventions

Norepinephrine; Dobutamine

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenethylamines; Ethylamines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3 first hours : strategy 1, norepinephrine alone with increased dose or norepinephrine + dobutamine 0.5 hour : wash-out (decrease of norepinephrine dose or weaning of dobutamine) 3 last hours : strategy 2, crossover, norepinephrine alone with increased dose or norepinephrine + dobutamine

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: November 14, 2017
• Study Start: January 15, 2018
• Primary Completion: November 1, 2019
• Study Completion: May 1, 2020
• Last Updated: November 14, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)