Dopexamine and Norepinephrine Compared With Epinephrine Alone in Septic Shock

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Dopexamine and norepinephrine

Epinephrine

About this trial

This is an interventional treatment trial for Septic Shock focused on measuring Splanchnic perfusion, hepatic damage, oxidative stress.

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Rennes University Hospital

Outcomes

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

Full Information

NCT ID

NCT00134212

First Posted

August 22, 2005

Last Updated

December 30, 2005

Sponsor

Rennes University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT00134212

Brief Title

Dopexamine and Norepinephrine Compared With Epinephrine Alone in Septic Shock

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2005

Overall Recruitment Status

Completed

Study Start Date

March 2002 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

June 2004 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Rennes University Hospital

4. Oversight

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Septic Shock

Keywords

Splanchnic perfusion, hepatic damage, oxidative stress.

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Single

Allocation

Randomized

Enrollment

20 (false)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Dopexamine and norepinephrine

Intervention Type

Drug

Intervention Name(s)

Epinephrine

Primary Outcome Measure Information:

Title

Gastric mucosal blood flow assessed using a laser-Doppler flowmeter

Secondary Outcome Measure Information:

Title

Systemic and pulmonary hemodynamics: systolic, diastolic and mean arterial, right atrial, systolic, diastolic and mean pulmonary arterial, and pulmonary capillary wedge pressures

Title

heart rate, stroke volume, cardiac output

Title

systemic and pulmonary vascular resistances

Title

arterial and venous blood gases and arterial lactate

Title

alanine and aspartate amino transferases

Title

bilirubin

Title

α-glutathione S-transferase

Title

nitric oxide and reactive oxygen species productions

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yannick Mallédant, MD

Organizational Affiliation

Rennes University Hospital

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Eric Bellissant, MD, PhD

Organizational Affiliation

Rennes University Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Philippe Seguin, MD

Organizational Affiliation

Rennes University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Rennes University Hospital

City

Rennes

ZIP/Postal Code

35033

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

9781719

Citation

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.

Results Reference

background

PubMed Identifier

7497722

Citation

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.

Results Reference

background

PubMed Identifier

16507156

Citation

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.

Results Reference

derived

Septic Shock

About this trial

Eligibility Criteria

Sites / Locations

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial