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

NCT00148278 | Completed Phase 2 DMC

• 3 other identifiers: AFSSAPS 990931AOM97123CIC0203/001
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 15

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.

Conditions

Septic Shock; Severe Sepsis; Infections

Keywords

Catecholamines; Septic shock

Outcome Measures

Primary Outcomes (1)

• 28 Day mortality

  28 Day

Secondary Outcomes (10)

• -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

Study Arms (2)

1

EXPERIMENTAL

norepinephrine plus dobutamine

Drug: norepinephrine and dobutamine

2

ACTIVE COMPARATOR

epinephrine

Drug: epinephrine plus placebo of dobutamine

Interventions

norepinephrine and dobutamine DRUG

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

1

epinephrine plus placebo of dobutamine DRUG

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

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Versailles: lead
• Assistance Publique - Hôpitaux de Paris: collaborator

Study Sites (15)

Réanimation Médicale - Hôpital Louis Mourier

Colombes, 92700, France

Location

Réanimation Polyvalente - Hôpital de Corbeil

Corbeil, 91100, France

Location

Service de Réanimation Médicale - Hôpital Poincaré

Garches, 92380, France

Location

Réanimation Médicale - Hôpital André Mignot

Le Chesnay, 78157, France

Location

Réanimation Polyvalente - Hôpital Dupuytren

Limoges, 87000, France

Location

Réanimation Polyvalente - Hôpital Nord

Marseille, 13009, France

Location

Réanimation Chirurgicale - Hôpital Central

Nancy, 54035, France

Location

Service de Réanimation Médicale - Hôpital Central

Nancy, 54035, France

Location

Service d'anesthésiologie - HIA Val de Grâce

Paris, 75005, France

Location

Réanimation Médicale - Hôpital Saint Louis

Paris, 75010, France

Location

Réanimation Polyvalente - Hôpital Saint Joseph

Paris, 75014, France

Location

Réanimation Médicale - Hôpital Georges Pompidou

Paris, 75908, France

Location

Réanimation Médicale - CHI de Poissy

Poissy, 78303, France

Location

Réanimation - CH Victor Provo

Roubaix, 59100, France

Location

Réanimation Polyvalente - Institut Gustave Roussy

Villejuif, 94800, France

Location

Related Publications (1)

• 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.

  PMID: 17720019 RESULT

MeSH Terms

Conditions

Shock, Septic; Sepsis; Infections

Interventions

Norepinephrine; Dobutamine; Epinephrine

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenethylamines; Ethylamines

Study Officials

• Djillali Annane, MD, PhD

  Assistance Publique Hôpitaux de Paris - University of Versailles

  STUDY DIRECTOR

• Eric Bellissant, MD, PhD

  CHU Rennes

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 1, 2005
• First Posted: September 7, 2005
• Study Start: October 1, 1999
• Primary Completion: December 1, 2004
• Study Completion: December 1, 2005
• Last Updated: July 22, 2010

Record last verified: 2010-07

Locations

FR (15)