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International Immune Tolerance Study

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ClinicalTrials.gov Identifier: NCT00212472
Recruitment Status : Terminated (The DSMB recommended stopping the study due to safety concerns.)
First Posted : September 21, 2005
Last Update Posted : December 7, 2009
Sponsor:
Collaborator:
Manchester University NHS Foundation Trust
Information provided by:
New York Presbyterian Hospital

Study Description
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Brief Summary:
The purpose of this study is to see if a low-dose arm or a high dose-arm of immune tolerance is more effective in eliminating inhibitors in patients with hemophilia A.

Condition or disease Intervention/treatment Phase
Hemophilia A With Inhibitors Drug: Factor VIII concentrates Other: Low-dose treatment Other: High-dose treatment Not Applicable

Detailed Description:
Subjects will be randomized into a low-dose or high-dose immune tolerance regimen and this study will compare the success rates, the time to achieve tolerance,the complications and the cost of both regimens.It will also aim to identify predictors of successful immune tolerance.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 134 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An International Randomised Controlled Trial Of Immune Tolerance Induction
Study Start Date : July 2002
Estimated Primary Completion Date : December 2010
Estimated Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: 1
Low-dose treatment (50 FVIII u/kg three times a week).
 Drug: Factor VIII concentrates
To be determined at the discretion of the investigator.
Other: Low-dose treatment
50 FVIII u/kg three times a week.
Active Comparator: 2
High-dose treatment (200 FVIII u/kg per day).
 Drug: Factor VIII concentrates
To be determined at the discretion of the investigator.
Other: High-dose treatment
200 FVIII u/kg per day.


Outcome Measures
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Primary Outcome Measures :
  1. Success-rate and partial success-rate [ Time Frame: Up to 69 months ]
  2. The time from the start of ITI to successful tolerance [ Time Frame: Up to 33 months ]
  3. The comparative cost-effectiveness of the two treatment arms [ Time Frame: Up to 69 months ]
  4. A comparative assessment of morbidity between the two treatment arms including: number of intercurrent bleeds, infections and number of hospital in-patient days. [ Time Frame: Up to 69 months ]
  5. The inhibitor recurrence (relapse) rate in the first twelve months after successful ITI. [ Time Frame: Up to 45 months ]

Secondary Outcome Measures :
  1. The dose-regimen, success rate and time to ITI, [ Time Frame: Up to 69 months ]
  2. The starting inhibitor titre, success rate and time to ITI, [ Time Frame: Up to 69 months ]
  3. The peak historical inhibitor titre, success rate and time to ITI, [ Time Frame: Up to 69 months ]
  4. The peak inhibitor titre after starting ITI, success rate and time to success, [ Time Frame: Up to 69 months ]
  5. The age at the time of inhibitor detection, success-rate and time to success, [ Time Frame: Up to 69 months ]
  6. The number of factor VIII treatment days between inhibitor detection and initiation of ITI, success of ITI. [ Time Frame: Up to 69 months ]
  7. The type of concentrate used (von Willebrand factor-containing, monoclonal or recombinant), success rate and time to success, [ Time Frame: Up to 69 months ]
  8. The effect of interim infections/immunisations, success rate and time to success, [ Time Frame: Up to 69 months ]
  9. The effect of treatment interruption, success rate and time to success. [ Time Frame: Up to 69 months ]

Eligibility Criteria
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Ages Eligible for Study:   up to 7 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00212472


  Show 39 Study Locations
Sponsors and Collaborators
New York Presbyterian Hospital
Manchester University NHS Foundation Trust
Investigators
Principal Investigator: Donna M DiMichele, MD Weill Cornell Medical College-NY Presybetrian Hospital
Principal Investigator: Charles Hay, MD Manchester Royal Infirmary
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: Donna DiMichele, MD, New York Presbyterian Hospital
ClinicalTrials.gov Identifier: NCT00212472     History of Changes
Other Study ID Numbers: ITI
First Posted: September 21, 2005    Key Record Dates
Last Update Posted: December 7, 2009
Last Verified: October 2009

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
 Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants