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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
History of Changes
  Purpose

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.


Condition Intervention Phase
Septic Shock
 Drug: Dopexamine and norepinephrine
Drug: Epinephrine
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

MedlinePlus related topics: Shock
U.S. FDA Resources

Further study details as provided by Rennes University Hospital:

Primary Outcome Measures:
  • Gastric mucosal blood flow assessed using a laser-Doppler flowmeter

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 20
Study Start Date: March 2002
Estimated Study Completion Date: June 2004
Detailed Description:

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.

  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

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00134212

Locations
France
Rennes University Hospital
Rennes, France, 35033
Sponsors and Collaborators
Rennes University Hospital
Investigators
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
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

ClinicalTrials.gov Identifier: NCT00134212     History of Changes
Other Study ID Numbers: AFSSAPS 020193, LOC-H/01-08, CIC0203/008
Study First Received: August 22, 2005
Last Updated: December 30, 2005
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Rennes University Hospital:
Splanchnic perfusion, hepatic damage, oxidative stress.

Additional relevant MeSH terms:
Shock
Shock, Septic
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Epinephrine
Dopexamine
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
Vasodilator Agents

ClinicalTrials.gov processed this record on May 19, 2013