Low-dose ITI Strategy for Children in Hemophilia A With High-titer Inhibitor and Poor ITI Risk in China

Study Overview
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Brief Summary
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The study start on January 18, 2017. The Severe(FⅧ<1%) and moderate hemophilia A (FⅧ1%～5%)children with high titer inhibitor(historical peak inhibitor titer≥5BU ) combining with poor ITI risk(s) were enrolled. The low-dose ITI was alone or combined with immunosuppression.

Detailed Description
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Poor risk(s) includes:①peak historical inhibitor titer≥200BU ②inhibitor titer≥10BU before ITI initiation ③peak inhibitor titer during ITI≥200BU ④time to titer decline to<10BU before ITI≥24 months ⑤age≥8 years at start of ITI ⑥ITI initiated ≥5 years after inhibitor diagnosis ⑦interruptions in ITI≥2 weeks in duration. The low-dose ITI strategy consist of FⅧ（25-50IU/kg）alone or combining with immunosuppression: prednisone and Rituximab when the inhibitor titer ≥40BU ml/ml before or during ITI.

Official Title
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Beijing Children's Hospital, Capital Medical University

Conditions
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Hemophilia A With Inhibitor

Intervention / Treatment
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* Drug: Coagulation Factor VIII
* Drug: Prednisone
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males from 1 to 14 years old severe or moderate hemophilia A; inhibitors positive before ITI started. Exclusion Criteria: Females <1 or >14 years old hemophilia B or mild haemophilia A; inhibitor negative before ITI started.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 14 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ITI strategy<br>The low-dose ITI was Coagulation Factor VIII (50IU/kg, every other day) alone or combined with prednisone (2mg Kg-1/day, one month, then taper in three months) depending on the tendency of inhibitor, and Rituximab (375mg/square meter every week for 4 weeks) when the inhibitor titer ≥40BU/ml before or during ITI.Inhibitor and hemorrhage should be retested and recorded periodically. | Drug: Coagulation Factor VIII<br>* Domastic plasma derived factor FVIII (with intermidiate vWF) 50IU/kg every other day<br>Drug: Prednisone<br>* 2mg/kg every day for 4 weeks then typering in 3 months<br>Drug: Rituximab<br>* 375mg/Square meter for consecutive 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate | Success rate | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Bleeding Rate | How many times for all types of bleeding | 2 year | 
| Annualized Joint Bleeding Rate | How many times for joint bleeding | 2 year | 
| Success time | How long to success | 2 years |