Norepinephrine Plus Dobutamine Versus Epinephrine Alone for the Management of Septic Shock - Full Text View

Sponsors and Collaborators:	University of Versailles Assistance Publique - Hôpitaux de Paris
Information provided by:	University of Versailles
ClinicalTrials.gov Identifier:	NCT00148278

Purpose

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.

Condition	Intervention	Phase
Septic Shock Severe Sepsis Infections	Drug: norepinephrine and dobutamine Drug: epinephrine plus placebo of dobutamine	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Prospective, Multicenter, Randomized, Double-Blind Study Comparing Safety and Efficacy of Norepinephrine Plus Dobutamine Versus Epinephrine Alone in Septic Shock.

Resource links provided by NLM:

MedlinePlus related topics: Sepsis

Drug Information available for: Norepinephrine Epinephrine bitartrate Epinephrine Dobutamine Dobutamine hydrochloride Dobutamine tartrate Dobutamine lactobionate Norepinephrine bitartrate

U.S. FDA Resources

Further study details as provided by University of Versailles:

Primary Outcome Measures:

28 Day mortality [ Time Frame: 28 Day ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

-28-day survival distribution [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
-Survival rate at days 14, 28, 90, 6 months and 1 year. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
-Rate of patients with secondary care limitation [ Time Frame: one year ] [ Designated as safety issue: No ]
-Organ failure between randomization and day 28. [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
-Serious adverse events between randomization and exit of intensive care unit. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
-Onset of a reversible clinical event between randomization and exit of intensive care unit (bronchospasm, cutaneous rash, tachycardia) [ Time Frame: one year ] [ Designated as safety issue: Yes ]
-Time on vasopressors [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
-Time in intensive care unit [ Time Frame: one year ] [ Designated as safety issue: Yes ]
-Time in hospital [ Time Frame: one year ] [ Designated as safety issue: Yes ]
-Costs [ Time Frame: Day 90 ] [ Designated as safety issue: No ]

Enrollment:	330
Study Start Date:	October 1999
Study Completion Date:	December 2005
Primary Completion Date:	December 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental norepinephrine plus dobutamine	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
2: Active Comparator epinephrine	Drug: 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

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00148278

Locations

France
Service de Réanimation Médicale - Hôpital Poincaré
Garches, France, 92380
Service de Réanimation Médicale - Hôpital Central
Nancy, France, 54035
Réanimation Polyvalente - Institut Gustave Roussy
Villejuif, France, 94800
Réanimation Polyvalente - Hôpital Dupuytren
Limoges, France, 87000
Réanimation Médicale - Hôpital Louis Mourier
Colombes, France, 92700
Réanimation Polyvalente - Hôpital de Corbeil
Corbeil, France, 91100
Réanimation Chirurgicale - Hôpital Central
Nancy, France, 54035
Réanimation Médicale - Hôpital André Mignot
Le Chesnay, France, 78157
Réanimation Médicale - Hôpital Georges Pompidou
Paris, France, 75908
Réanimation Médicale - CHI de Poissy
Poissy, France, 78303
Réanimation - CH Victor Provo
Roubaix, France, 59100
Réanimation Polyvalente - Hôpital Nord
Marseille, France, 13009
Réanimation Médicale - Hôpital Saint Louis
Paris, France, 75010
Service d'anesthésiologie - HIA Val de Grâce
Paris, France, 75005
Réanimation Polyvalente - Hôpital Saint Joseph
Paris, France, 75014

Sponsors and Collaborators

University of Versailles

Assistance Publique - Hôpitaux de Paris

Investigators

Study Director:	Djillali Annane, MD, PhD	Assistance Publique Hôpitaux de Paris - University of Versailles
Study Chair:	Eric Bellissant, MD, PhD	CHU Rennes

More Information

Publications:

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.

Responsible Party:	Assistance Publique Hôpitaux de Paris ( Djillali Annane )
Study ID Numbers:	AFSSAPS 990931, AOM97123, CIC0203/001
Study First Received:	September 1, 2005
Last Updated:	February 19, 2008
ClinicalTrials.gov Identifier:	NCT00148278 History of Changes
Health Authority:	France: Afssaps - French Health Products Safety Agency; France: Ministry of Health

Keywords provided by University of Versailles:

Catecholamines
Septic shock

Study placed in the following topic categories:

Systemic Inflammatory Response Syndrome
Neurotransmitter Agents
Adrenergic alpha-Agonists
Adrenergic beta-Agonists
Adrenergic Agents
Benzocaine
Anti-Asthmatic Agents
Cardiovascular Agents
Adrenergic Agonists
Dobutamine

Inflammation
Sepsis
Mydriatics
Shock
Shock, Septic
Norepinephrine
Vasoconstrictor Agents
Peripheral Nervous System Agents
Epinephrine
Bronchodilator Agents

Additional relevant MeSH terms:

Respiratory System Agents
Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Cardiotonic Agents
Physiological Effects of Drugs
Infection
Adrenergic Agonists
Pathologic Processes
Therapeutic Uses
Vasoconstrictor Agents
Epinephrine
Systemic Inflammatory Response Syndrome
Adrenergic alpha-Agonists
Adrenergic beta-Agonists

Sympathomimetics
Anti-Asthmatic Agents
Cardiovascular Agents
Protective Agents
Dobutamine
Pharmacologic Actions
Inflammation
Sepsis
Mydriatics
Shock
Autonomic Agents
Norepinephrine
Shock, Septic
Peripheral Nervous System Agents
Bronchodilator Agents

ClinicalTrials.gov processed this record on July 02, 2009