Clinical Trial: A Comparison Study of Bypassing Agent Therapy With and Without Tranexamic Acid in Haemophilia A Patients With Inhibitor

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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-vi

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: Oslo University Hospital

Current Primary Outcome: 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.


Original Primary Outcome: 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.


Current Secondary Outcome: 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.


Original Secondary Outcome: DIC or thrombosis events associated with different treatment regimens. [ Time Frame: 2 years ]

DIC parametres 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 dyspne, chest pain, legg swelling or disconfort/pain were recorded.


Information By: Oslo University Hospital

Dates:
Date Received: February 15, 2013
Date Started: October 2011
Date Completion:
Last Updated: February 28, 2013
Last Verified: February 2013