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

University of Versailles

Status and phase: Completed; Phase 3; Phase 2

Conditions: Infections; Severe Sepsis; Septic Shock

Treatments: Drug: epinephrine plus placebo of dobutamine; Drug: norepinephrine and dobutamine

Study type: Interventional

Funder types: Other

Identifiers

NCT00148278

AFSSAPS 990931

CIC0203/001

AOM97123

Details and patient eligibility

About

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.

Full 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.

Enrollment: 330 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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330 participants in 2 patient groups

1

Experimental group

Description:

norepinephrine plus dobutamine

Treatment:

Drug: norepinephrine and dobutamine

2

Active Comparator group

Description:

epinephrine

Treatment:

Drug: epinephrine plus placebo of dobutamine