Norepinephrine vs Norepinephrine and Dobutamine in Cardiogenic Shock

Study Overview
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Brief Summary
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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

Official Title
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Norepinephrine vs Norepinephrine and Dobutamine in Cardiogenic Shock : a Randomised, Opened, Cross-over Study. Heart SHOCK-NORDOB Study

Conditions
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Cardiogenic Shock

Intervention / Treatment
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* Drug: Norepinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: < 18 years old Pregnancy Inclusion in other drug study Poisonings with cardiotoxicants Patient with intra-aortic ballon pump, extracorporeal life support Patient under guardianship

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Norepinephrine alone<br>Administration of norepinephrine with increasing dose | Drug: Norepinephrine<br>* 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.<br>* Other names: Dobutamine;|
| Active Comparator: Norepinephrine plus Dobutamine<br>Administration of norepinephrine and dobutamine | Drug: Norepinephrine<br>* 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.<br>* Other names: Dobutamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemodynamic parameters | Measure of heart rate (bpm), | Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5 | 
| Occurence of arrythmia | Notification of atrial arrythmia | Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5 | 
| Change in hemodynamic parameters | Cumulated dose of catecholamines | Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5 | 
| All-cause mortality | Mortality | Day 28 | 
| Change in hemodynamic parameters | Arterial blood pressure (mmHg) | Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5 | 
| Change in metabolic parameters | SVcO2 (%) | Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5 | 
| Change in metabolic parameters | Lactate clearance (mmol/L) | Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5 | 
| Change in metabolic parameters | Muscular oxygen saturation (%) | Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5 | 
| Change in metabolic parameters | Urine output (mL/h) | Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5 | 
| Change in metabolic parameters | Mottle (mottle score) | Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5 | 
| Occurence of arrythmia | Notification of ventricular arrythmia | Hour 0, Hour 1, Hour 3, Hour 3.5, Hour 4,5, Hour 5.5, Hour 6.5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dobutamine, Shock, Norepinephrine