Early Lactate-Directed Therapy in the Intensive Care Unit (ICU) - Full Text View

Sponsors and Collaborators:	Erasmus Medical Center Medical Center Rijnmond Zuid, Rotterdam St. Fransiscus Gasthuis, Rotterdam Reinier de Graaf Hospital, Delft Albert Schweitzer Hospital, Netherlands
Information provided by:	Erasmus Medical Center
ClinicalTrials.gov Identifier:	NCT00270673

Purpose

Blood lactate levels have long been related to tissue hypoxia, a severe condition in critically ill patients associated with the development of organ system failure and subsequent death. Increased blood lactate levels and failure to normalize blood lactate levels during treatment have been associated with increased morbidity and mortality. However, evidence of improved clinical outcome of lactate-directed therapy is limited and difference in the use of blood lactate monitoring in the intensive care unit exists between hospitals. This warrants a study on the efficacy of early blood lactate-directed therapy. In this study the efficacy of 8 hours of early lactate-directed therapy (therapy aimed at resolving tissue hypoxia that is guided by serial blood lactate levels) will be compared with 8 hours of control group therapy (without lactate measurement).

Condition	Intervention	Phase
Tissue Hypoxia Hyperlactatemia	Procedure: Early lactate-directed therapy	Phase III

Drug Information available for: Lactic acid Ammonium lactate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Early Lactate-Directed Therapy on the ICU: A Randomized Controlled Trial

Further study details as provided by Erasmus Medical Center:

Primary Outcome Measures:

In-hospital mortality

Secondary Outcome Measures:

ICU mortality
Day-28 mortality
APACHE II,SOFA and hemodynamic variables
Use of health care resources
Pre-specified subgroup analyses within non-sepsis stratum:
Neuro critical care (traumatic brain injury, neurovascular conditions, neuro-oncological conditions)
Cardiac arrest
Remaining group (without neuro critical care and cardiac arrest)
Pre-specified subgroup analyses within sepsis stratum:
Sepsis and severe sepsis
Septic shock

Estimated Enrollment:	350
Study Start Date:	February 2006
Study Completion Date:	March 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients admitted to the general ICU with an admission lactate level of ≥ 3,0 mmol/l
Written informed consent

Exclusion Criteria:

Liver failure
Post liver surgery
Age < 18 years
Do not resuscitate status
Contraindication to central venous or arterial catheterization
Epileptic seizures (shortly before or during admission)
Evident aerobic cause of hyperlactatemia
Judgement of treating physician that study participation is undesirable for medical, medical-ethical or other reasons

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00270673

Locations

Netherlands
Erasmus MC University Medical Center
Rotterdam, Netherlands
Medical Center Rijnmond Zuid
Rotterdam, Netherlands
St. Fransiscus Gasthuis
Rotterdam, Netherlands
Reinier de Graaf Hospital
Delft, Netherlands
Ikazia Hospital
Rotterdam, Netherlands

Sponsors and Collaborators

Erasmus Medical Center

Medical Center Rijnmond Zuid, Rotterdam

St. Fransiscus Gasthuis, Rotterdam

Reinier de Graaf Hospital, Delft

Albert Schweitzer Hospital, Netherlands

Investigators

Study Chair:	Jan Bakker, MD, PhD	Erasmus MC University Medical Center Rotterdam
Principal Investigator:	Tim C Jansen, MD	Erasmus MC University Medical Center Rotterdam

More Information

Publications:

Zhang H, Vincent JL. Oxygen extraction is altered by endotoxin during tamponade-induced stagnant hypoxia in the dog. Circ Shock. 1993 Jul;40(3):168-76.

Ronco JJ, Fenwick JC, Tweeddale MG, Wiggs BR, Phang PT, Cooper DJ, Cunningham KF, Russell JA, Walley KR. Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans. JAMA. 1993 Oct 13;270(14):1724-30.

Crowl AC, Young JS, Kahler DM, Claridge JA, Chrzanowski DS, Pomphrey M. Occult hypoperfusion is associated with increased morbidity in patients undergoing early femur fracture fixation. J Trauma. 2000 Feb;48(2):260-7.

Claridge JA, Crabtree TD, Pelletier SJ, Butler K, Sawyer RG, Young JS. Persistent occult hypoperfusion is associated with a significant increase in infection rate and mortality in major trauma patients. J Trauma. 2000 Jan;48(1):8-14; discussion 14-5.

Blow O, Magliore L, Claridge JA, Butler K, Young JS. The golden hour and the silver day: detection and correction of occult hypoperfusion within 24 hours improves outcome from major trauma. J Trauma. 1999 Nov;47(5):964-9.

Rossi AF, Khan DM, Hannan R, Bolivar J, Zaidenweber M, Burke R. Goal-directed medical therapy and point-of-care testing improve outcomes after congenital heart surgery. Intensive Care Med. 2005 Jan;31(1):98-104. Epub 2004 Dec 1.

Polonen P, Ruokonen E, Hippelainen M, Poyhonen M, Takala J. A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients. Anesth Analg. 2000 May;90(5):1052-9.

Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE. Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet. 2005 Mar 5-11;365(9462):871-5. Erratum in: Lancet. 2005 Jul 9-15;366(9480):122.

Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77.

Gozzoli V, Treggiari MM, Kleger GR, Roux-Lombard P, Fathi M, Pichard C, Romand JA. Randomized trial of the effect of antipyresis by metamizol, propacetamol or external cooling on metabolism, hemodynamics and inflammatory response. Intensive Care Med. 2004 Mar;30(3):401-7. Epub 2004 Jan 13.

Manthous CA, Hall JB, Olson D, Singh M, Chatila W, Pohlman A, Kushner R, Schmidt GA, Wood LD. Effect of cooling on oxygen consumption in febrile critically ill patients. Am J Respir Crit Care Med. 1995 Jan;151(1):10-4.

Bruder N, Lassegue D, Pelissier D, Graziani N, Francois G. Energy expenditure and withdrawal of sedation in severe head-injured patients. Crit Care Med. 1994 Jul;22(7):1114-9.

Raat NJ, Verhoeven AJ, Mik EG, Gouwerok CW, Verhaar R, Goedhart PT, de Korte D, Ince C. The effect of storage time of human red cells on intestinal microcirculatory oxygenation in a rat isovolemic exchange model. Crit Care Med. 2005 Jan;33(1):39-45; discussion 238-9.

Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999 Feb 11;340(6):409-17. Erratum in: N Engl J Med 1999 Apr 1;340(13):1056.

Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF. Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet. 2002 Nov 2;360(9343):1395-6.

De Backer D, Creteur J, Dubois MJ, Sakr Y, Vincent JL. Microvascular alterations in patients with acute severe heart failure and cardiogenic shock. Am Heart J. 2004 Jan;147(1):91-9.

Moerer O, Schmid A, Hofmann M, Herklotz A, Reinhart K, Werdan K, Schneider H, Burchardi H. Direct costs of severe sepsis in three German intensive care units based on retrospective electronic patient record analysis of resource use. Intensive Care Med. 2002 Oct;28(10):1440-6. Epub 2002 Aug 17.

Study ID Numbers:	2005-334
Study First Received:	December 23, 2005
Last Updated:	April 24, 2008
ClinicalTrials.gov Identifier:	NCT00270673
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Erasmus Medical Center:

Lactate
Tissue hypoxia
Intensive care
Goal- directed therapy

Study placed in the following topic categories:

Signs and Symptoms
Signs and Symptoms, Respiratory
Anoxia

ClinicalTrials.gov processed this record on February 12, 2009