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

This study has been completed.
Sponsor:
Collaborator:
Assistance Publique - Hôpitaux de Paris
Information provided by:
University of Versailles
ClinicalTrials.gov Identifier:
NCT00148278
First received: September 1, 2005
Last updated: July 21, 2010
Last verified: July 2010
History of Changes
  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 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Shock
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
Experimental: 1
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
Active Comparator: 2
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
Réanimation Médicale - Hôpital Louis Mourier
Colombes, France, 92700
Réanimation Polyvalente - Hôpital de Corbeil
Corbeil, France, 91100
Service de Réanimation Médicale - Hôpital Poincaré
Garches, France, 92380
Réanimation Médicale - Hôpital André Mignot
Le Chesnay, France, 78157
Réanimation Polyvalente - Hôpital Dupuytren
Limoges, France, 87000
Réanimation Polyvalente - Hôpital Nord
Marseille, France, 13009
Service de Réanimation Médicale - Hôpital Central
Nancy, France, 54035
Réanimation Chirurgicale - Hôpital Central
Nancy, France, 54035
Réanimation Médicale - Hôpital Georges Pompidou
Paris, France, 75908
Réanimation Polyvalente - Hôpital Saint Joseph
Paris, France, 75014
Réanimation Médicale - Hôpital Saint Louis
Paris, France, 75010
Service d'anesthésiologie - HIA Val de Grâce
Paris, France, 75005
Réanimation Médicale - CHI de Poissy
Poissy, France, 78303
Réanimation - CH Victor Provo
Roubaix, France, 59100
Réanimation Polyvalente - Institut Gustave Roussy
Villejuif, France, 94800
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:

Responsible Party: Djillali Annane, Assistance Publique Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00148278     History of Changes
Other Study ID Numbers: AFSSAPS 990931, AOM97123, CIC0203/001
Study First Received: September 1, 2005
Last Updated: July 21, 2010
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Ministry of Health

Keywords provided by University of Versailles:
Catecholamines
Septic shock

Additional relevant MeSH terms:
Sepsis
Shock
Shock, Septic
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Epinephrine
Dobutamine
Norepinephrine
Epinephryl borate
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Mydriatics
Adrenergic alpha-Agonists
Sympathomimetics
Vasoconstrictor Agents
Cardiovascular Agents
Cardiotonic Agents

ClinicalTrials.gov processed this record on May 21, 2013