Dopexamine and Norepinephrine Compared With Epinephrine Alone in Septic Shock

NCT00134212 | Completed Phase 2

• 3 other identifiers: AFSSAPS 020193LOC-H/01-08CIC0203/008
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Septic Shock

Keywords

Splanchnic perfusion, hepatic damage, oxidative stress.

Outcome Measures

Primary Outcomes (1)

• Gastric mucosal blood flow assessed using a laser-Doppler flowmeter

Secondary Outcomes (8)

• 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

Interventions

Dopexamine and norepinephrine DRUG

Epinephrine DRUG

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
• 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.

You may not qualify if:

• Pregnant women
• Patients with a history of esophageal or gastric disease
• Patients with a history of esophageal or gastric surgery

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (1)

Rennes University Hospital

Rennes, 35033, France

Location

Related Publications (3)

• 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. doi: 10.1097/00003246-199810000-00012.

  PMID: 9781719 BACKGROUND

• 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. doi: 10.1097/00003246-199512000-00008.

  PMID: 7497722 BACKGROUND

• 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. doi: 10.1186/cc4827.

  PMID: 16507156 DERIVED

MeSH Terms

Conditions

Shock, Septic

Interventions

dopexamine; Norepinephrine; Epinephrine

Condition Hierarchy (Ancestors)

Sepsis; Infections; 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

Study Officials

• Yannick Mallédant, MD

  Rennes University Hospital

  STUDY DIRECTOR

• Eric Bellissant, MD, PhD

  Rennes University Hospital

  STUDY CHAIR

• Philippe Seguin, MD

  Rennes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 22, 2005
• First Posted: August 24, 2005
• Study Start: March 1, 2002
• Study Completion: June 1, 2004
• Last Updated: January 2, 2006

Record last verified: 2005-12

Locations

FR (1)