A Comparison Study of Bypassing Agent Therapy With and Without Tranexamic Acid in Haemophilia A Patients With Inhibitor (BPATXAS)

February 28, 2013 updated by: Pål Andre Holme, Oslo University Hospital

Whole Blood Clot Stability and Thrombin Generating Capacity Following Treatment With Bypassing Agents (BPA) With and Without and Tranexamic Acid (TXA) in Haemophilia A Patients With inhibitor-an In-vivo Prospective Crossover Study

Activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rFVIIa) are the only two drugs that are available to treat bleeds in haemophilia A patients with high titer inhibitors. However, management of bleeds in these patients can be challenging due to variation in response and lack of standardized methods to monitor the effect. We hypothesized that significant increase in whole blood clot stability could be achieved when tranexamic acid was given concomitantly with bypassing-agents while thrombin generation remains unaffected. In this prospective crossover study the effect of aPCC and rFVIIa with and without TXA on clot stability and thrombin generation capacity (ETP) were studied, using thromboelastography (ROTEM) and thrombin generation assay (TGA), respectively. In addition, the risk of thrombosis and disseminated intravascular coagulation (DIC) was assessed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients receive the first day aPCC (75IU/kg) and aPCC in addition to TXA (20mg/kg orally) the second day. After a 14 days washout period they crosse over using rFVIIa (90 µg/kg) otherwise the same experimental setup. Blood sampling is performed at baseline, 15, 30, 60, 120, 180 and 240 minutes post-treatment.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Oslo, Norway, 0424
        • Oslo University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Haemophilia patients with high titer inhibitors or high-responding inhibitors, aged between 18-65 and no history of aspirin or NSAID use within the last 14 days were eligible for the study.

Exclusion Criteria:

  • Patients with renal failure, liver disease, infected with immune deficiency virus (HIV), platelet count <150x109/L, acquired haemophilia, ongoing bleeding, hypersensitivity to TXA or a history of arterial or venous thrombosis were excluded from the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: aPCC, aPCC + TXA
aPCC 75IU/kg i.v aPCC 75IU/kg i.v +TXA 20mg/kg
Drug: aPCC, aPCC + TXA
Feiba 75 IU/kg i.v Feiba 75 IU/kg i.v +Cyklokapron 20 mg/kg p.o
Other Names:
  • Feiba i.v
  • Feiba i.v + Cyklokapron
Drug: rFVIIa, rFVIIa + TXA
NovoSeven 90 µg/kg i.v NovoSeven 90 µg/kg i.v + Cyklokapron 20 mg/kg
Other Names:
  • NovoSeven 90 µg/kg i.v
  • NovoSeven 90 µg/kg i.v + Cyklokapron 20 mg/kg
Active Comparator: rFVIIa, rFVIIa + TXA
rFVIIa 90 µg/kg i.v rFVIIa 90 µg/kg i.v + TXA 20 mg/kg
Drug: aPCC, aPCC + TXA
Feiba 75 IU/kg i.v Feiba 75 IU/kg i.v +Cyklokapron 20 mg/kg p.o
Other Names:
  • Feiba i.v
  • Feiba i.v + Cyklokapron
Drug: rFVIIa, rFVIIa + TXA
NovoSeven 90 µg/kg i.v NovoSeven 90 µg/kg i.v + Cyklokapron 20 mg/kg
Other Names:
  • NovoSeven 90 µg/kg i.v
  • NovoSeven 90 µg/kg i.v + Cyklokapron 20 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clot stability and thrombin generation capacity following treatment with bypassing agents with and without tranexamic acid.
Time Frame: 2 years
MCF (maximum clot formation/mm x 100-1), AUC (area under the elasticity curve AUC, mm• 100 s-1) were used as the primary outcome measures for evaluating clot stability and (ETP) the coagulable state.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DIC or thrombosis events associated with different treatment regimens.
Time Frame: 2 years
DIC parameters such as aPTT, PT/INR, platelet count, fibrinogen and D-dimer with the scoring system proposed by the International Society of Thrombosis and Haemostasis were used to monitor DIC in addition to common clinical signs associated with DIC were records. Symptoms or clinical signs of thrombosis such as dyspnea, chest pain, legg swelling or discomfort/pain were recorded.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oslo University Hospital

Investigators

  • Principal Investigator: PÅL A Holme, MD PhD, Oslo University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

February 15, 2013

First Submitted That Met QC Criteria

February 25, 2013

First Posted (Estimate)

February 27, 2013

Study Record Updates

Last Update Posted (Estimate)

March 1, 2013

Last Update Submitted That Met QC Criteria

February 28, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCTnr. 2010-022668-11
  • 2010-022668-11 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hereditary Factor VIII Deficiency Disease With Inhibitor

Clinical Trials on aPCC, aPCC + TXA

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Rwanda

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe