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

Septic Shock Clinical Trial

— CATS  

Official title:

Prospective, Multicenter, Randomized, Double-Blind Study Comparing Safety and Efficacy of Norepinephrine Plus Dobutamine Versus Epinephrine Alone in Septic Shock.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00148278
• Other study ID #: AFSSAPS 990931
• Secondary ID: AOM97123CIC0203/
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 1, 2005
• Last updated: July 21, 2010
• Start date: October 1999
• Est. completion date: December 2005

Study information

• Verified date: July 2010
• Source: University of Versailles
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: December 2005
• Est. primary completion date: December 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infections
• Septic Shock
• Severe Sepsis
• Shock
• Shock, Septic

Intervention

Drug:
• norepinephrine and dobutamine
continuous infusion of norepinephrine titrated to maintain a mean arterial pressure at 70mmHg or more and dobutamine could be added as a continuous infusion when cardiac index was of less than 2.5 liters per squared meter of body surface
• epinephrine plus placebo of dobutamine
epinephrine was titrated to maintain a mean arterial pressure at 70mmHg or more and placebo of dobutamine was titrated in case of a cardiac index lower than 2.5 liters per squared meters of body surface

Locations

Country	Name	City	State
France	Réanimation Médicale - Hôpital Louis Mourier	Colombes
France	Réanimation Polyvalente - Hôpital de Corbeil	Corbeil
France	Service de Réanimation Médicale - Hôpital Poincaré	Garches
France	Réanimation Médicale - Hôpital André Mignot	Le Chesnay
France	Réanimation Polyvalente - Hôpital Dupuytren	Limoges
France	Réanimation Polyvalente - Hôpital Nord	Marseille
France	Réanimation Chirurgicale - Hôpital Central	Nancy
France	Service de Réanimation Médicale - Hôpital Central	Nancy
France	Réanimation Médicale - Hôpital Georges Pompidou	Paris
France	Réanimation Médicale - Hôpital Saint Louis	Paris
France	Réanimation Polyvalente - Hôpital Saint Joseph	Paris
France	Service d'anesthésiologie - HIA Val de Grâce	Paris
France	Réanimation Médicale - CHI de Poissy	Poissy
France	Réanimation - CH Victor Provo	Roubaix
France	Réanimation Polyvalente - Institut Gustave Roussy	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
University of Versailles	Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (1)

Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troché 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 randomi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	28 Day mortality		28 Day	Yes
Secondary	-28-day survival distribution		Day 28	Yes
Secondary	-Survival rate at days 14, 28, 90, 6 months and 1 year.		one year	Yes
Secondary	-Rate of patients with secondary care limitation		one year	No
Secondary	-Organ failure between randomization and day 28.		Day 28	Yes
Secondary	-Serious adverse events between randomization and exit of intensive care unit.		one year	Yes
Secondary	-Onset of a reversible clinical event between randomization and exit of intensive care unit (bronchospasm, cutaneous rash, tachycardia)		one year	Yes
Secondary	-Time on vasopressors		Day 90	No
Secondary	-Time in intensive care unit		one year	Yes
Secondary	-Time in hospital		one year	Yes
Secondary	-Costs		Day 90	No