Blood Coagulation DisorderPhase 1/2NCT00493272
Dilutional Coagulopathy in Patients Undergoing Elective Surgery
A Phase 1/2 study testing Fibrinogen in people with Blood Coagulation Disorder, run by Christian Fenger-Eriksen at 1 site in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Blood Coagulation Disorder
- What is being tested?
- Fibrinogen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2007to Apr 2008
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- > 18 years
- Indication for performing cystectomia
- Written informed consent
Who cannot join
- 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
Show all 9Show fewer
- Liver failure defined as clinical relevant abnormal levels of ALAT
- Hypersensibility to Voluven, Haemocomplettan or ingredients
- Fertile women not using safe contraception
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Aarhus University Hospital, Department of Anaesthesiology
Dk-8200 Aarhus N
About this study
Official title: Fibrinogen vs Placebo for Improvement of Clot Strength
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.
Read the 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:
- 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
- Blood Coagulation Disorder
- Being tested
- Fibrinogen
- Keywords
- Blood coagulation disorder, acquired, Hemodilution, Fibrinogen, Hemostasis, HES
- Medical subject headings
- Blood Coagulation Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FibrinogenDrug
Also called Active drug
Fibrinogen behandling
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Nacl Receives: Drug: Fibrinogen |
| Fibrinogen | Active comparator | Fibrinogen Receives: Drug: Fibrinogen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dynamic whole blood clot formation.
Measured: 60 minutes
Secondary outcomes (1)
A) Single coagulation factor activities B) Platelet function C) Whole blood clot stability. D) Thrombin generation.
Measured: 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2007 (estimated)
- Study startJun 2007
- Primary completionApr 2008
- Study completionApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Blood Coagulation DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christian Fenger-Eriksen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Christian Fenger-Eriksen, Aarhus University Hospital
- Investigators
- Else Tønnesen, MD, Prof, Principal investigator, Aarhus University Hospital, Department of Anaesthesiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00493272
- Sponsor's protocol ID
- 20070037
- Status last verified
- Nov 2015
- First submitted
- 27 Jun 2007
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 9806670Damon 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.
PubMed 2442613Baldassarre 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.
PubMed 9024047de 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.
PubMed 11810130Fenger-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.
PubMed 15608046Fenger-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.
PubMed 16879481
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fibrinogen vs Placebo for Improvement of Clot Strength
- ClinicalTrials.gov ID
- NCT00493272
- Acronym / sponsor ID
- 20070037
- Conditions
- Blood Coagulation Disorder
- Keywords
- Blood coagulation disorder, acquired, Hemodilution, Fibrinogen, Hemostasis, HES
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Christian Fenger-EriksenUniversity, hospital or other
- Study start
- Jun 2007
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 28 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: FibrinogenNacl |
| Fibrinogen | Active comparator | Drug: FibrinogenFibrinogen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- > 18 years
- Indication for performing cystectomia
- Written informed consent
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FibrinogenAlso: Active drugFibrinogen behandling | Drug | Fibrinogen, Placebo |
Primary outcome
Dynamic whole blood clot formation.
Time frame: 60 minutes
1 secondary outcome
A) Single coagulation factor activities B) Platelet function C) Whole blood clot stability. D) Thrombin generation.
Time frame: 60 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
- Background: PubMed 9806670Jamnicki 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.
- Background: PubMed 2442613Damon 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.
- Background: PubMed 9024047Baldassarre 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.
- Background: PubMed 11810130de 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.
- Background: PubMed 15608046Fenger-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.
- Background: PubMed 16879481Fenger-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Else Tønnesen, MD, Prof principal investigator
Aarhus University Hospital, Department of Anaesthesiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fibrinogen in people with Blood Coagulation Disorder, run by Christian Fenger-Eriksen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dynamic whole blood clot formation. (time frame: 60 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00493272, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2015.