Dopexamine and Norepinephrine Compared With Epinephrine Alone in Septic Shock - Full Text View

Sponsor:	Rennes University Hospital
Information provided by:	Rennes University Hospital
ClinicalTrials.gov Identifier:	NCT00134212

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 II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind, Active Control, Parallel Assignment, Efficacy Study
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:

Drug Information available for: Norepinephrine Epinephrine bitartrate Epinephrine Dopexamine Dopexamine hydrochloride Norepinephrine bitartrate

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:

Schmidt W, Hacker A, Gebhard MM, Martin E, Schmidt H. Dopexamine attenuates endotoxin-induced microcirculatory changes in rat mesentery: role of beta2 adrenoceptors. Crit Care Med. 1998 Oct;26(10):1639-45.

Tighe D, Moss R, Heywood G, al-Saady N, Webb A, Bennett D. Goal-directed therapy with dopexamine, dobutamine, and volume expansion: effects of systemic oxygen transport on hepatic ultrastructure in porcine sepsis. Crit Care Med. 1995 Dec;23(12):1997-2007.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Seguin P, Laviolle B, Guinet P, Morel I, Malledant Y, Bellissant E. Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: a randomized study [NCT00134212]. Crit Care. 2006 Feb;10(1):R32.

Study ID Numbers:	AFSSAPS 020193, LOC-H/01-08, CIC0203/008
Study First Received:	August 22, 2005
Last Updated:	December 30, 2005
ClinicalTrials.gov Identifier:	NCT00134212 History of Changes
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Rennes University Hospital:

Splanchnic perfusion, hepatic damage, oxidative stress.

Additional relevant MeSH terms:

Respiratory System Agents
Vasodilator Agents
Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Dopamine Agonists
Infection
Adrenergic Agonists
Dopexamine
Pathologic Processes
Therapeutic Uses
Vasoconstrictor Agents
Epinephrine
Systemic Inflammatory Response Syndrome

Adrenergic alpha-Agonists
Adrenergic beta-Agonists
Sympathomimetics
Anti-Asthmatic Agents
Cardiovascular Agents
Pharmacologic Actions
Inflammation
Sepsis
Mydriatics
Shock
Autonomic Agents
Norepinephrine
Shock, Septic
Dopamine Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on November 27, 2009