Dilutional Coagulopathy in Patients Undergoing Elective Surgery

This study has been completed.
Sponsor:
Information provided by:
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00493272
First received: June 27, 2007
Last updated: May 5, 2008
Last verified: May 2008
  Purpose

The purpose of the present study is to perform a comprehensive description of haemostasis parameters before and after haemodilution with Hydroxyethyl starch (HES) following acute bleeding during elective surgery. Moreover the study aims to test the in vivo haemostatic potential of fibrinogen concentrate in dilutional coagulopathy caused by HES in a clinical, prospective, placebo-controlled randomised setup.

We hypothesise; a) A coagulopathy is induced following in vivo haemodilution; b) the coagulopathy is improved or partially improved by fibrinogen.


Condition Intervention Phase
Blood Coagulation Disorder
Drug: Fibrinogen
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Diagnostic

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • Dynamic whole blood clot formation.

Secondary Outcome Measures:
  • A) Single coagulation factor activities B) Platelet function C) Whole blood clot stability. D) Thrombin generation.

Estimated Enrollment: 20
Study Start Date: June 2007
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Detailed Description:

Background Hydroxyethyl starch (HES) is a group of artificial colloid solutions widely used for plasma expansion and volume resuscitation. HES consist of branched chains of hydroxylated glucose molecules defined by average molecular weight, degree of hydroxyethylation, and C2/C6 ratio. Several clinical reports and in vitro experiments have documented an impaired coagulation system induced by haemodilution with HES and other colloid plasma expanders. The exact mechanisms responsible for HES induced coagulopahty are not fully understood although reduced levels of von Willebrand factor (vWF), acquired platelet dysfunction, reduced factor VIII levels, and dysfunctional fibrinogen polymerization seems to reflect an important aspect of the pathogenesis.

Experimental laboratory studies performed in our centre and verified by several other research groups have shown successful reversal of the colloid plasma expander induced coagulopathy by fibrinogen concentrate.10-13 So far, the present knowledge are based on laboratory experiments and animal studies. Hence, it appears desirable to perform a comprehensive description of haemostasis parameters following HES induced dilutional coagulopathy in an acute clinical bleeding situation.

Materials and Methods

Study design: Clinical, prospective, double-blind, randomised, place-controlled trial. Blood samples:

Primary end point:

Dynamic whole blood clot formation

Secondary end points:

A) Single coagulation factor activities B) Platelet function C) Whole blood clot stability. D) Thrombin generation

Perspectives:

Serious surgical and traumatic bleedings are common and associated with a high mortality rate. The present study can significantly contribute to our overall understanding of the mechanisms involved in HES induced dilutional coagulopathy.

  Eligibility

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

Inclusion Criteria:

  • > 18 years
  • Indication for performing cystectomia
  • Written informed consent

Exclusion Criteria:

  • Uses of acetyl-salicylic or non-steroid anti-inflammatory drugs 2 days prior to blood sampling.
  • Abnormal preoperative coagulations parameters (Platelets, PP, APTT, D- dimer, Fibrinogen, AT, TT)
  • Disseminated cancer and/or bone metastasis
  • Medical history of ischemic heart disease, claudicatio, or arteriosclerosis
  • Medical history of previous thrombo-embolic event
  • Renal failure defined as clinical relevant abnormal levels of creatinine
  • Liver failure defined as clinical relevant abnormal levels of ALAT
  • Hypersensibility to Voluven, Haemocomplettan or ingredients
  • Fertile women not using safe contraception
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493272

Locations
Denmark
Aarhus University Hospital, Department of Anaesthesiology
DK-8200 Aarhus N, Denmark
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: Else Tønnesen, MD, Prof Aarhus University Hospital, Department of Anaesthesiology
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00493272     History of Changes
Other Study ID Numbers: 20070037
Study First Received: June 27, 2007
Last Updated: May 5, 2008
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: National Board of Health

Keywords provided by University of Aarhus:
Blood coagulation disorder, acquired
Hemodilution
Fibrinogen
Hemostasis
HES

Additional relevant MeSH terms:
Blood Coagulation Disorders
Hemostatic Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Vascular Diseases

ClinicalTrials.gov processed this record on October 23, 2014