Evaluation of a Standardized Protocol for Thrombin Generation Assay

NCT03313531 | Completed FDA Drug

• 1 other identifier: TGA1
• Study Type: observational
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study is aims at determining the inter laboratory variation when using the thrombin generation assay calibrated automated thrombogram (TGA CAT). It is thus, not a clinical trial in its usual meaning. However, to achieve relevant test samples one patient will be treated with two different study drugs as part of the trial and therefore, approval by Läkemedelsverket is needed. Test plasma samples will be sent out to five participating centers in the Scandinavian countries (Gothenburg and Stockholm, Sweden, Århus Denmark, Oslo Norway and Helsinki Finland) and coefficients of variance (CV) and level of agreement will be analyzed. To obtain representative plasma samples with a wide range of thrombin generation capacity (TGC), blood samples will be collected from research persons that has given informed consent to participate in the study. To obtain plasma with low TGC, blood samples will be drawn from patients with severe hemophilia (n=4)(study group 1), to obtain plasma with normal TGC, blood samples will be drawn from healthy volunteers (n=3)(study group 2) and to obtain plasma with high TGC, plasma will be collected from healthy volunteers (n=3)(study group 3) that at previous measurements have been shown to have a TGC\>2SD of the median of the control population. Moreover, one patient with severe hemophilia A (HA) will be treated with two factor FVIII concentrates, one with standard half- life (Advate™) and one with a pro-longed half-life (Adynovate™) at two separate occasions (Treated HA person). By taking repeated blood samples after administration, samples with a wide range of FVIII levels and TGC:s will be obtained. Moreover, the effect of using plasmas with low, normal and high TGC for normalization will be investigated. Plasma samples will be collected as soon as approval from the Swedish medical agency (SMA) has been obtained, we count on sending them to participating centers March 2017. All laboratory measurements, data analysis and report writing will be concluded before December 31 2017.

Conditions

Hemophilia A

Keywords

Thrombin generation; variability; level of agreement; hemophilia

Outcome Measures

Primary Outcomes (3)

• Inter lab variability

  Coefficient of Variation (CV) i plasma samples with high, normal and low thrombin genration capacity

  May 2017

• Inter lab variability

  Coefficient of Variation (CV) i plasma samples from a patient treated with Advate

  May 2017

• Inter lab variability

  Coefficient of Variation (CV) and level of agreement i plasma samples from a patient treated with Adynovate

  May 2017

Secondary Outcomes (1)

• Inter lab variability

  May 2017

Study Arms (4)

Study group 1

Patients with severe hemophilia A

Diagnostic Test: Thrombin Generation Assay

Study group 2

Healthy volunteers

Diagnostic Test: Thrombin Generation Assay

Study group 3

Healthy volunteers ) that at previous measurements have been shown to have a TGC\>2SD of the median of the control population.

Diagnostic Test: Thrombin Generation Assay

Treated HA person

One patient with severe hemophilia A (HA) will be treated with two factor FVIII concentrates, one with standard half- life (Advate™) and one with a pro-longed half-life (Adynovate™) at two separate occasions

Diagnostic Test: Thrombin Generation Assay; Drug: Treatment with recombinant coagulation factor

Interventions

Thrombin Generation Assay DIAGNOSTIC_TEST

Inter lab variation and level of agreement will be determined

Study group 1; Study group 2; Study group 3; Treated HA person

Treatment with recombinant coagulation factor DRUG

To obtain a wide range of thrombingeneration levels, one person (Treated HA person) will recieve one injection of Advate and one injection of Adynovate respectively

Treated HA person

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient with severe hemophilia A

You may qualify if:

• For patients with severe hemophilia A (study group 1)(n=4) that has not received any factor concentrate within 72 hours: Diagnosis of severe hemophilia, with regular check-ups at the hemophilia center at SUS, Malmö and willingness to participate
• For healthy controls (n=3) (study group 2): Willingness to participate
• For healthy controls with a documented high TGC (study group 3): Willingness to participate

You may not qualify if:

• For patients with severe hemophilia A (study group 1)(n=4) that has not received any factor concentrate within 72 hours: Intake of any other pharmaceutical product known to have an effect on the coagulation system the last 14 days, to the judgement of the including investigator
• For healthy controls (n=3) (study group 2): Any disorder known to affect the coagulation system and intake of any drug known to affect the coagulation system the last 14 days before blood sampling , to the judgement of the including investigator.
• For healthy controls with a documented high TGC (study group 3): Any disorder known to affect the coagulation system and intake of any drug known to affect the coagulation system within the last 14 days before blood sampling, to the judgement of the including investigator.

Sponsors & Collaborators

• Lund University: lead
• Shire: collaborator

Study Sites (1)

Coagulation Unit, department of translational medicine

Malmo, 20502, Sweden

Location

Related Publications (9)

• Nair SC, Dargaud Y, Chitlur M, Srivastava A. Tests of global haemostasis and their applications in bleeding disorders. Haemophilia. 2010 Jul;16 Suppl 5:85-92. doi: 10.1111/j.1365-2516.2010.02304.x.

  PMID: 20590862 BACKGROUND

• Trossaert M, Regnault V, Sigaud M, Boisseau P, Fressinaud E, Lecompte T. Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation assay to assess the bleeding phenotype. J Thromb Haemost. 2008 Mar;6(3):486-93. doi: 10.1111/j.1538-7836.2007.02861.x. Epub 2007 Nov 28.

  PMID: 18047548 BACKGROUND

• Dargaud Y, Trzeciak MC, Bordet JC, Ninet J, Negrier C. Use of calibrated automated thrombinography +/- thrombomodulin to recognise the prothrombotic phenotype. Thromb Haemost. 2006 Nov;96(5):562-7.

  PMID: 17080211 BACKGROUND

• Lecompte T, Wahl D, Perret-Guillaume C, Hemker HC, Lacolley P, Regnault V. Hypercoagulability resulting from opposite effects of lupus anticoagulants is associated strongly with thrombotic risk. Haematologica. 2007 May;92(5):714-5. doi: 10.3324/haematol.10577.

  PMID: 17488705 BACKGROUND

• Freyburger G, Macouillard G, Labrouche S, Sztark F. Coagulation parameters in patients receiving dabigatran etexilate or rivaroxaban: two observational studies in patients undergoing total hip or total knee replacement. Thromb Res. 2011 May;127(5):457-65. doi: 10.1016/j.thromres.2011.01.001. Epub 2011 Jan 31.

  PMID: 21277622 BACKGROUND

• Hacquard M, Perrin J, Lelievre N, Vigneron C, Lecompte T. Inter-individual variability of effect of 7 low molecular weight antithrombin-dependent anticoagulants studied in vitro with calibrated automated thrombography. Thromb Res. 2011 Jan;127(1):29-34. doi: 10.1016/j.thromres.2010.07.024. Epub 2010 Sep 17.

  PMID: 20850172 BACKGROUND

• Dargaud Y, Luddington R, Gray E, Lecompte T, Siegemund T, Baglin T, Hogwood J, Regnault V, Siegemund A, Negrier C. Standardisation of thrombin generation test--which reference plasma for TGT? An international multicentre study. Thromb Res. 2010 Apr;125(4):353-6. doi: 10.1016/j.thromres.2009.11.012. Epub 2009 Nov 26.

  PMID: 19942257 BACKGROUND

• Perrin J, Depasse F, Lecompte T; French-speaking CAT group and under the aegis of GEHT; French-speaking CAT group (all in France unless otherwise stated):; French-speaking CAT group all in France unless otherwise stated. Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma. Thromb Res. 2015 Jul;136(1):125-30. doi: 10.1016/j.thromres.2014.12.015. Epub 2014 Dec 24.

  PMID: 25563679 BACKGROUND

• Hemker HC, Giesen P, Al Dieri R, Regnault V, de Smedt E, Wagenvoord R, Lecompte T, Beguin S. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb. 2003;33(1):4-15. doi: 10.1159/000071636.

  PMID: 12853707 BACKGROUND

MeSH Terms

Conditions

Hemophilia A

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Jan Astermark, MD PhD

  Department of hematology, Skane University hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2017
• First Posted: October 18, 2017
• Study Start: April 15, 2017
• Primary Completion: January 28, 2019
• Study Completion: January 28, 2019
• Last Updated: January 29, 2019

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)