Brief Title
Individualizing Hemophilia Prophylaxis Using Thromboelastography
Official Title
Individualizing Hemophilia Prophylaxis Using Thromboelastography
Brief Summary
Currently dosing for prophylaxis is not individualized, and the general approach is to use a
dose of 25-40 units/kg given 3 times per week or every other day. One of the issues with
weight-based dosing is the possible over-treatment. This is likely due to the fact that
laboratory tests are not sensitive enough at the low levels to support decision-making. The
Thromboelastograph (TEG®) and Thromboelastometry (ROTEM®) are coagulation devices, which
assess the dynamics of clot formation over time and have several characteristics which
suggest they may provide important information for individualized prophylaxis treatment for
our patients.
Detailed Description
This is a pilot study in children and adults with severe hemophilia A that utilizes the
TEG/ROTEM to personalize their prophylaxis treatment.
Primary objectives:
• Assess the feasibility of TEG/ROTEM-guided modification of the current prophylaxis regimen
for individuals with severe hemophilia A. Specifically, to:
- Test and refine the operational protocol for using TEG/ROTEM to guide factor dosing
- Estimate the proportion of hemophilia A patients whose dose will be modified based on
TEG/ROTEM results
- Monitor short term safety of patients whose dose has been modified.
Secondary objectives
- Perform thrombin generation assays to provide additional evidence supporting the
TEG/ROTEM-guided dosing.
- Obtain preliminary data on the economic impact of TEG/ROTEM-guided hemophilia A dosing
regimens.
- Obtain preliminary data on the potential improvement of subject/family burden resulting
from TEG/ROTEM-guided regimen using generic and specific quality of life tools.
The study period will consist of screening, pharmacokinetic (PK) study and follow-up. For
subjects whose prophylaxis treatment regimen is modified, the follow-up period will include 3
follow-up clinic visits and 4 follow-up phone calls; these patients will remain on study for
approximately 6 months following completion of the PK-study then will have an end of the
study visit (visit 9). Subjects whose treatment regimen is not altered will end their study
participation after Visit 2 and continuing with their current prophylaxis regimen.
Study endpoints: A safety review will be conducted after the first 6 subjects complete 30
days with the extended prophylaxis treatment. If no safety issues are identified, the study
will proceed, and second safety review will be after an additional 8 subjects complete 30
days of extended treatment. If a subject has two or more spontaneous bleeds in 30 days, the
subject will be removed from the study. For subjects who did not have bleeds and completed at
least 6 months of the study, ongoing prophylactic treatment will be decided by their treating
physician.
Study Type
Interventional
Primary Outcome
Feasibility of TEG/ROTEM-guided prophylaxis modification for patients, assessed by estimated proportion of patients whose dose is modified.
Secondary Outcome
Thrombin generation assay will be performed to provide additional evidence supporting the TEG/ROTEM-guided dosing.
Condition
Hemophilia A
Intervention
Thromboelastography/Thromboelastometry-Guided Treatment Regimen
Study Arms / Comparison Groups
Severe Hemophilia A Subjects
Description: The results of the TEG/ROTEM assay (specifically the R time/CT) will be used to determine the prophylaxis treatment regimen.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
18
Start Date
May 20, 2014
Completion Date
December 31, 2017
Primary Completion Date
December 31, 2017
Eligibility Criteria
Inclusion Criteria:
- Males, 5-70 years, inclusive
- Plasma FVIII activity <1% documented (Laboratory result or MD documentation of Severe
Hemophilia A diagnosis)
- Currently prescribed prophylaxis treatment regimen infusing ≥3 times a week
- Willing to alter their prophylaxis treatment regimen per study protocol
Exclusion Criteria:
- Bleeding disorder(s) other than Hemophilia A
- Current inhibitor (>0.6BU)
- Thrombocytopenia (platelet count <100,000K/µL since it can alter TEG®/ROTEM® results)
- Creatinine >2x the upper limit of normal (indicating potential platelet dysfunction)
- Prothrombin time >3 seconds above the upper limit of normal (indicating potential
liver dysfunction)
- Any concurrent clinically significant major disease, frequent bleeding pattern or
history of non-compliance that, in the opinion of the investigator, would make the
subject unsuitable for enrollment
- Participation within the past 30 days in any other clinical study involving
investigational drugs
- Planned major surgery within 30 days prior to screening or during the study period
- Current use of any medication known to have effects on the coagulation system
Gender
Male
Ages
5 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
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Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02582060
Organization ID
14-00030
Responsible Party
Principal Investigator
Study Sponsor
Children's Hospital Los Angeles
Study Sponsor
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Verification Date
February 2019