Alternative Dosing And Prevention of Transfusions (ADAPT)
Study Details
Study Description
Brief Summary
ADAPT is a prospective cohort study at Jinja Regional Referral Hospital (JRRH) primarily to assess the effect of hydroxyurea on blood transfusion utilization and secondarily to determine the feasibility of PK-guided hydroxyurea dosing.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Early Phase 1 |
Detailed Description
Hypothesis
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There will be a 50% reduction in the rate of blood transfusions received during the hydroxyurea treatment period compared with the pre-treatment period.
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A PK-guided starting dose will be generated for 80% of participants.
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Participants on PK-guided hydroxyurea treatment will require 25% fewer blood transfusions during their first year of hydroxyurea than those on dose escalation.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment All participants will receive an individualized PK hydroxyurea assessment. Participants for whom the PK-process successfully generates a dose in the predicted treatment range of 15-35 mg/kg/day, will start on that personalized dose. Participants for whom the process does not generate a starting hydroxyurea dose in the predicted treatment range, due to potential pitfalls in lab draws, serum storage, sample processing, or hydroxyurea analysis, will start at a default dose of 20.0 ± 2.5 mg/kg/day. For all participants, the hydroxyurea dose will be adjusted as needed based on blood counts to establish the optimal dose. Where necessary, a weekly dosing average will be determined, so that treatment can occur solely with locally available and affordable 500mg hydroxyurea capsules. |
Drug: Hydroxyurea
All participants will receive an individualized PK hydroxyurea assessment. Participants for whom the PK-process successfully generates a dose in the predicted treatment range of 15-35 mg/kg/day, will start on that personalized dose. Participants for whom the process does not generate a starting hydroxyurea dose in the predicted treatment range, due to potential pitfalls in lab draws, serum storage, sample processing, or hydroxyurea analysis, will start at a default dose of 20.0 ± 2.5 mg/kg/day. For all participants, the hydroxyurea dose will be adjusted as needed based on blood counts to establish the optimal dose. Where necessary, a weekly dosing average will be determined, so that treatment can occur solely with locally available and affordable 500mg hydroxyurea capsules.
|
Outcome Measures
Primary Outcome Measures
- To compare the rates of blood transfusions overall and by specific indications in children with sickle cell anaemia (SCA), prior to and during hydroxyurea treatment [One year (Enrollment - Month 15)]
The incidence rate ratio of transfusions overall and by specific indication during the screening phase as compared to the treatment phase
Secondary Outcome Measures
- To determine clinical and laboratory factors associated with reduction in blood transfusions for children with SCA on hydroxyurea treatment [One year (Enrollment - Month 15)]
The relative risk of transfusion due to the most common clinical diagnoses and laboratory factors for children with SCA on hydroxyurea treatment.
Other Outcome Measures
- To assess the feasibility and safety of a pharmacokinetic (PK)-based hydroxyurea dose within the predicted treatment range for Uganda [One year (Enrollment - Month 15)]
The percentage of successful PK-dosing assessments, defined as assessments completed in entirety resulting in the generation of a PK-guided starting dose. The incidence rate ratio of clinical and laboratory adverse events among those started on the PK-guided hydroxyurea dose during the screening phase compared with the treatment phase.
- To quantify rates of SCA-related complications (including stroke, sepsis, and pain) in participants receiving PK-guided hydroxyurea dosing and within the overall cohort on hydroxyurea treatment [One year (Enrollment - Month 15)]
The number of participants with sickle cell-related complications (including stroke, sepsis and pain) in participants receiving PK-guided hydroxyurea dosing compared to the rate of events in the default dosing group.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients with documented HbSS disease
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Age: ≥ 12 months and ≤ 10 years of age, at the time of enrollment
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Parent or guardian willing and able to provide informed consent
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Able to comply with all study related treatments, evaluations, and follow-up
Exclusion Criteria:
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Current hydroxyurea treatment (or within the past 6 months)
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Regular blood transfusions (6 or more within the past 12 months)
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Transfusion within the last 30 days (temporary exclusion)
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Known malignancy or other known chronic illnesses including but not limited to active tuberculosis, renal disease
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Current participation in other therapeutic clinical trials, or within 6 months of prior disease-modifying treatments
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Jinja Regional Referral Hospital (JRRH), Department of Paediatrics, Sickle Cell Clinic | Jinja | Uganda |
Sponsors and Collaborators
- Children's Hospital Medical Center, Cincinnati
- Jinja Regional Referral Hospital (JRRH), Sickle Cell Clinic, Jinja, Uganda
Investigators
- Study Director: Russell Ware, MD, PhD, Children's Hospital Medical Center, Cincinnati
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ADAPT