Dilutional Coagulopathy in Patients Undergoing Elective Surgery

NCT ID: NCT00493272

Last Updated: 2015-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2008-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Blood Coagulation Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Placebo

Nacl

Group Type PLACEBO_COMPARATOR

Fibrinogen

Intervention Type DRUG

Fibrinogen behandling

Fibrinogen

Fibrinogen

Group Type ACTIVE_COMPARATOR

Fibrinogen

Intervention Type DRUG

Fibrinogen behandling

Interventions

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Fibrinogen

Fibrinogen behandling

Intervention Type DRUG

Other Intervention Names

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Active drug

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Christian Fenger-Eriksen

OTHER

Sponsor Role lead

Responsible Party

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Christian Fenger-Eriksen

PhD MD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Else Tønnesen, MD, Prof

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital, Department of Anaesthesiology

Locations

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Aarhus University Hospital, Department of Anaesthesiology

Dk-8200 Aarhus N, , Denmark

Site Status

Countries

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Denmark

References

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Jamnicki M, Zollinger A, Seifert B, Popovic D, Pasch T, Spahn DR. Compromised blood coagulation: an in vitro comparison of hydroxyethyl starch 130/0.4 and hydroxyethyl starch 200/0.5 using thrombelastography. Anesth Analg. 1998 Nov;87(5):989-93. doi: 10.1097/00000539-199811000-00002.

Reference Type BACKGROUND
PMID: 9806670 (View on PubMed)

Damon L, Adams M, Stricker RB, Ries C. Intracranial bleeding during treatment with hydroxyethyl starch. N Engl J Med. 1987 Oct 8;317(15):964-5. doi: 10.1056/NEJM198710083171517. No abstract available.

Reference Type BACKGROUND
PMID: 2442613 (View on PubMed)

Baldassarre S, Vincent JL. Coagulopathy induced by hydroxyethyl starch. Anesth Analg. 1997 Feb;84(2):451-3. doi: 10.1097/00000539-199702000-00040. No abstract available.

Reference Type BACKGROUND
PMID: 9024047 (View on PubMed)

de Jonge E, Levi M, Buller HR, Berends F, Kesecioglu J. Decreased circulating levels of von Willebrand factor after intravenous administration of a rapidly degradable hydroxyethyl starch (HES 200/0.5/6) in healthy human subjects. Intensive Care Med. 2001 Nov;27(11):1825-9. doi: 10.1007/s001340101107. Epub 2001 Sep 26.

Reference Type BACKGROUND
PMID: 11810130 (View on PubMed)

Fenger-Eriksen C, Anker-Moller E, Heslop J, Ingerslev J, Sorensen B. Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate. Br J Anaesth. 2005 Mar;94(3):324-9. doi: 10.1093/bja/aei052. Epub 2004 Dec 17.

Reference Type BACKGROUND
PMID: 15608046 (View on PubMed)

Fenger-Eriksen C, Ingerslev J, Sorensen B. Coagulopathy induced by colloid plasma expanders--search for an efficacious haemostatic intervention. Acta Anaesthesiol Scand. 2006 Aug;50(7):899-900. doi: 10.1111/j.1399-6576.2006.01054.x. No abstract available.

Reference Type BACKGROUND
PMID: 16879481 (View on PubMed)

Other Identifiers

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20070037

Identifier Type: -

Identifier Source: org_study_id