Norepinephrine Plus Dobutamine Versus Epinephrine Alone for the Management of Septic Shock

Phase 2

Completed

• Conditions: Septic Shock; Severe Sepsis; Infections
• Interventions: Drug: norepinephrine and dobutamine; Drug: epinephrine plus placebo of dobutamine

• Registration Number: NCT00148278
• Lead Sponsor: University of Versailles

Brief Summary

Catecholamines infusion is a major component of septic shock management. International guidelines recommend that norepinephrine should be preferred to epinephrine, though phase III trials are lacking. The present study aimed at comparing the efficacy and safety of norepinephrine plus dobutamine to that of epinephrine in adults with septic shock.

Detailed Description

The french Conference on Consensus on catecholamines use in septic shock has underlined the importance of carrying out a clinical trial to clarify the use of epinephrine, norepinephrine and dobutamine in the management of multiple organ failure associated with severe sepsis. The main objective of the study was therefore to compare the effects of the combination of dobutamine and norepinephrine to those of epinephrine alone in patients with septic shock. In this purpose, patients were randomly assigned to receive either epinephrine or norepinephrine plus dobutamine and drugs were titrated to maintain blood pressure over 70 mmHg. Main outcome was 28-day mortality.

Study Timeline

• Study Start: 1999-10
• Primary Completion: 2004-12
• Study First Submitted: 2005-09-01
• Study First Submitted QC: 2005-09-02
• Study First Posted: 2005-09-07
• Study Completion: 2005-12
• Status Verified: 2010-07
• Last Update Submitted: 2010-07-21
• Last Update Posted: 2010-07-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 330

Inclusion Criteria

• Adults over 18 years
• Informed consent

Presenting from less than 7 days :

• One or more infectious site
• At least 2 of the following criteria: temperature > 38°C or < 36.5°C, respiratory rate > 20 breaths per min or PaCO2 < 32 mmHg or mechanical ventilation, heart rate > 90 beats/min, white blood cell count > 12,000/mm3 or < 4,000/mm3
• At least 2 of the following criteria: PaO2/FiO2 ratio <280 mmHg (if mechanical ventilation, urinary output of less than 0.5 mL/kg of body weight or < 30 mL/h at least 1 hour, plasma lactate > 2 mmol/L, platelet count < 100,000 /mm3

And presenting from at least 24 hours:

• Systolic blood pressure < 90 mmHg or mean blood pressure < 70 mmHg (for at least 30 min);
• 1000 mL fluid replacement or pulmonary capillary wedge pressure > 12 mmHg
• Dopamine infusion at 15 µg/kg/min for at least 1 hour, or epinephrine or norepinephrine in first intention

Exclusion Criteria

• Pregnant woman
• Obstructive cardiomyopathy
• Acute coronary disease
• Non infectious shock
• Care limitation
• White blood cell count < 500 /mm3

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	norepinephrine and dobutamine	norepinephrine plus dobutamine
2	epinephrine plus placebo of dobutamine	epinephrine

Primary Outcome Measures

Name	Time	Method
28 Day mortality	28 Day

Secondary Outcome Measures

Name	Time	Method
-28-day survival distribution	Day 28
-Survival rate at days 14, 28, 90, 6 months and 1 year.	one year
-Rate of patients with secondary care limitation	one year
-Organ failure between randomization and day 28.	Day 28
-Serious adverse events between randomization and exit of intensive care unit.	one year
-Onset of a reversible clinical event between randomization and exit of intensive care unit (bronchospasm, cutaneous rash, tachycardia)	one year
-Time on vasopressors	Day 90
-Time in intensive care unit	one year
-Time in hospital	one year
-Costs	Day 90

Trial Locations

Locations (15)

Réanimation Polyvalente - Hôpital Nord; 🇫🇷 Marseille, France

Service de Réanimation Médicale - Hôpital Central; 🇫🇷 Nancy, France

Réanimation Médicale - Hôpital André Mignot; 🇫🇷 Le Chesnay, France

Réanimation Médicale - Hôpital Louis Mourier; 🇫🇷 Colombes, France

Service de Réanimation Médicale - Hôpital Poincaré; 🇫🇷 Garches, France

Réanimation Médicale - CHI de Poissy; 🇫🇷 Poissy, France

Réanimation Polyvalente - Hôpital Saint Joseph; 🇫🇷 Paris, France

Réanimation Polyvalente - Hôpital Dupuytren; 🇫🇷 Limoges, France

Réanimation Chirurgicale - Hôpital Central; 🇫🇷 Nancy, France

Réanimation - CH Victor Provo; 🇫🇷 Roubaix, France

Réanimation Polyvalente - Institut Gustave Roussy; 🇫🇷 Villejuif, France

Service d'anesthésiologie - HIA Val de Grâce; 🇫🇷 Paris, France

Réanimation Médicale - Hôpital Saint Louis; 🇫🇷 Paris, France

Réanimation Médicale - Hôpital Georges Pompidou; 🇫🇷 Paris, France

Réanimation Polyvalente - Hôpital de Corbeil; 🇫🇷 Corbeil, France