Clinical trial NCT00148278: Norepinephrine Plus Dobutamine Versus Epinephrine Alone for the Management of Septic Shock
Official title: Prospective, Multicenter, Randomized, Double-Blind Study Comparing Safety and Efficacy of Norepinephrine Plus Dobutamine Versus Epinephrine Alone in Septic Shock.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Septic Shock
Severe Sepsis
Infections
Keywords: Catecholamines
Septic shock
Lead sponsor: University of Versailles
Sponsor class: OTHER
Collaborators: name: Assistance Publique - Hôpitaux de Paris
First posted: 2005-09-07
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 28 Day mortality
timeFrame: 28 Day
Secondary outcomes:
measure: -28-day survival distribution
timeFrame: Day 28
measure: -Survival rate at days 14, 28, 90, 6 months and 1 year.
timeFrame: one year
measure: -Rate of patients with secondary care limitation
timeFrame: one year
measure: -Organ failure between randomization and day 28.
timeFrame: Day 28
measure: -Serious adverse events between randomization and exit of intensive care unit.
timeFrame: one year
measure: -Onset of a reversible clinical event between randomization and exit of intensive care unit (bronchospasm, cutaneous rash, tachycardia)
timeFrame: one year
measure: -Time on vasopressors
timeFrame: Day 90
measure: -Time in intensive care unit
timeFrame: one year
measure: -Time in hospital
timeFrame: one year
measure: -Costs
timeFrame: Day 90
Other outcomes:
Locations:
city: Colombes
country: France
facility: Réanimation Médicale - Hôpital Louis Mourier
city: Corbeil
country: France
facility: Réanimation Polyvalente - Hôpital de Corbeil
city: Garches
country: France
facility: Service de Réanimation Médicale - Hôpital Poincaré
city: Le Chesnay
country: France
facility: Réanimation Médicale - Hôpital André Mignot
city: Limoges
country: France
facility: Réanimation Polyvalente - Hôpital Dupuytren
city: Marseille
country: France
facility: Réanimation Polyvalente - Hôpital Nord
city: Nancy
country: France
facility: Réanimation Chirurgicale - Hôpital Central
city: Nancy
country: France
facility: Service de Réanimation Médicale - Hôpital Central
city: Paris
country: France
facility: Service d'anesthésiologie - HIA Val de Grâce
city: Paris
country: France
facility: Réanimation Médicale - Hôpital Saint Louis
city: Paris
country: France
facility: Réanimation Polyvalente - Hôpital Saint Joseph
city: Paris
country: France
facility: Réanimation Médicale - Hôpital Georges Pompidou
city: Poissy
country: France
facility: Réanimation Médicale - CHI de Poissy
city: Roubaix
country: France
facility: Réanimation - CH Victor Provo
city: Villejuif
country: France
facility: Réanimation Polyvalente - Institut Gustave Roussy
Study officials:
affiliation: Assistance Publique Hôpitaux de Paris - University of Versailles
name: Djillali Annane, MD, PhD
role: STUDY_DIRECTOR
affiliation: CHU Rennes
name: Eric Bellissant, MD, PhD
role: STUDY_CHAIR
References:
citation: Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troche G, Ricard JD, Nitenberg G, Papazian L, Azoulay E, Bellissant E; CATS Study Group. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet. 2007 Aug 25;370(9588):676-84. doi: 10.1016/S0140-6736(07)61344-0.