Alternative Dosing And Prevention of Transfusions (ADAPT)

Study Overview
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Brief Summary
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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.

Detailed Description
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Hypothesis There will be a 50% reduction in the rate of blood transfusions received during the hydroxyurea treatment period compared with the pre-treatment period. A PK-guided starting dose will be generated for 80% of participants. Participants on PK-guided hydroxyurea treatment will require 25% fewer blood transfusions during their first year of hydroxyurea than those on dose escalation.

Official Title
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Alternative Dosing And Prevention of Transfusions (ADAPT): A Prospective Study to Reduce Transfusion Requirements for Children With Sickle Cell Anemia Using Pharmacokinetics-based Hydroxyurea Dosing

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Hydroxyurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with documented HbSS disease Age: ≥ 12 months and ≤ 10 years of age, at the time of enrollment Parent or guardian willing and able to provide informed consent Able to comply with all study related treatments, evaluations, and follow-up Exclusion Criteria: Current hydroxyurea treatment (or within the past 6 months) Regular blood transfusions (6 or more within the past 12 months) Transfusion within the last 30 days (temporary exclusion) Known malignancy or other known chronic illnesses including but not limited to active tuberculosis, renal disease Current participation in other therapeutic clinical trials, or within 6 months of prior disease-modifying treatments

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 10 Years

Sexes Eligible for Study
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All

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
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | The incidence rate ratio of transfusions overall and by specific indication during the screening phase as compared to the treatment phase | One year (Enrollment - Month 15) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine clinical and laboratory factors associated with reduction in blood transfusions for children with SCA on hydroxyurea treatment | The relative risk of transfusion due to the most common clinical diagnoses and laboratory factors for children with SCA on hydroxyurea treatment. | One year (Enrollment - Month 15) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Hydroxyurea, Transfusion