Dopexamine and Norepinephrine Compared With Epinephrine Alone in Septic Shock

This study has been completed.
Sponsor:
Information provided by:
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT00134212
First received: August 22, 2005
Last updated: December 30, 2005
Last verified: December 2005

August 22, 2005
December 30, 2005
March 2002
Not Provided
Gastric mucosal blood flow assessed using a laser-Doppler flowmeter
Gastric mucosal blood flow assessed using a laser-Doppler flowmeter.
Complete list of historical versions of study NCT00134212 on ClinicalTrials.gov Archive Site
  • Systemic and pulmonary hemodynamics: systolic, diastolic and mean arterial, right atrial, systolic, diastolic and mean pulmonary arterial, and pulmonary capillary wedge pressures
  • heart rate, stroke volume, cardiac output
  • systemic and pulmonary vascular resistances
  • arterial and venous blood gases and arterial lactate
  • alanine and aspartate amino transferases
  • bilirubin
  • α-glutathione S-transferase
  • nitric oxide and reactive oxygen species productions
  • -Systemic and pulmonary hemodynamics: systolic, diastolic and mean arterial, right atrial, systolic, diastolic and mean pulmonary arterial, and pulmonary capillary wedge pressures,
  • - heart rate, stroke volume, cardiac output,
  • - systemic and pulmonary vascular resistances,
  • - arterial and venous blood gases and arterial lactate,
  • - alanine and aspartate amino transferases,
  • - bilirubin,
  • - α-glutathione S-transferase,
  • - nitric oxide and reactive oxygen species productions.
Not Provided
Not Provided
 
Dopexamine and Norepinephrine Compared With Epinephrine Alone in Septic Shock
Prospective, Randomized Study on Two Parallel Groups Comparing Dopexamine and Norepinephrine in Combination to Epinephrine Alone on Systemic and Pulmonary Hemodynamics, Gastric Mucosal Perfusion, and Oxidative Stress in Septic Shock

In septic shock, when volume resuscitation fails to restore mean arterial pressure, catecholamines such as dopamine, dobutamine, epinephrine, or norepinephrine are used, either alone or in combination. Although they allow hemodynamic success to be obtained, they can leave some regional blood flows impaired, especially the hepatosplanchnic perfusion, which contributes to multiple organ failure.

Dopexamine is a structural and synthetic analog of dopamine that exerts systemic and gut vasodilation and stimulates cardiac contraction. In experimental models, dopexamine has been shown to exert anti-inflammatory properties and to protect the hepatic ultra structure. The combination of dopexamine and norepinephrine could therefore constitute an interesting alternative in treating septic shock patients. This study will test the efficacy (on gastric mucosal blood flow, hepatic damage and oxidative stress) and safety of the combination of dopexamine and norepinephrine (compared to those of epinephrine alone) in the treatment of patients with septic shock.

Objective: To compare the combination of dopexamine and norepinephrine with epinephrine alone on gastric mucosal blood flow (GMBF), hepatic damage and oxidative stress in septic shock.

Setting: Surgical intensive care unit in a university hospital.

Design: Prospective, randomized, controlled study on 2 parallel groups.

Patients: Adults fulfilling usual criteria for septic shock.

Interventions: Systemic hemodynamics, GMBF (laser-Doppler), plasma α-glutathione S-transferase, aspartate aminotransferase, alanine aminotransferase and malondialdehyde were assessed just before catecholamine infusion (T0), as soon as mean arterial pressure (MAP) reached 70-80 mmHg (T1), and 2 (T2) and 6 (T3) hours after T1. Drugs were titrated from 0.2 µg/kg/min with 0.2 µg/kg/min increments every 3 min for epinephrine and norepinephrine, and from 0.5 µg/kg/min with 0.5 µg/kg/min increments every 3 min for dopexamine.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Treatment
Septic Shock
  • Drug: Dopexamine and norepinephrine
  • Drug: Epinephrine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
June 2004
Not Provided

Inclusion Criteria:

  • Adults over 18 years
  • Informed consent
  • Septic shock with:

    • evidence of infection;
    • at least 3 of the following criteria: temperature > 38°C or < 36.5°C; respiratory rate > 20 breaths per minute 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: plasma lactate > 2 mmol/L or unexplained metabolic acidosis (pH < 7.3); hypoxemia defined by PaO2 < 70 mmHg at room air or a PaO2/FiO2 ratio < 280 mmHg (or < 200 mmHg if pneumonia was the source of sepsis) or need for mechanical ventilation; urine output < 30 mL/h for at least 2 hours despite a fluid challenge of at least 500mL; a platelet count < 100,000/mm3, a decrease of 50% from previous value, or unexplained coagulopathy (prothrombin time < 60% and elevated fibrin degradation products > 10 μg/mL);
    • systolic blood pressure < 90 mmHg despite an optimal volume loading defined by a pulmonary capillary wedge pressure > 12 mmHg.

Exclusion Criteria:

  • Pregnant women
  • Patients with a history of esophageal or gastric disease
  • Patients with a history of esophageal or gastric surgery
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00134212
AFSSAPS 020193, LOC-H/01-08, CIC0203/008
Not Provided
Not Provided
Rennes University Hospital
Not Provided
Study Director: Yannick Mallédant, MD Rennes University Hospital
Study Chair: Eric Bellissant, MD, PhD Rennes University Hospital
Principal Investigator: Philippe Seguin, MD Rennes University Hospital
Rennes University Hospital
December 2005

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP