An International Randomised Controlled Trial Of Immune Tolerance Induction

Inclusion Criteria:

- Severe hemophilia A (FVIII level <1%).

- A maximum historical inhibitor titer of between 5 BU and 200 BU that must be
confirmed once prior to the beginning of ITI.

- The inhibitor titer should be <10 BU at the start of ITI, confirmed once.

- The inhibitor must be present for <24 months when ITI begins.

- Maximum age of 7 at the start of ITI.

- Willingness to comply with the protocol.

Exclusion Criteria:

- Moderate or mild hemophilia A (FVIII level >1%).

- Spontaneous disappearance of the inhibitor prior to ITI.

- Historical maximum inhibitor titer <5 BU or > 200 BU before starting ITI.

- Inhibitor titer > 10 BU at the start of ITI.

- Inhibitor present for more than 24 months before starting ITI.

- Systemic immunomodulatory drug therapy during immune tolerance e.g. corticosteroids
(< 5 days every 2 months maximum dose 2 mg/kg or 60 mg/day), azathioprine,
cyclophosphamide, high-dose immunoglobulin or the use of a protein A column or
plasmapheresis.

- Age > 7 years at the start of ITI.

- Inability or unwillingness to comply with the protocol.

- Previous attempt at ITI.