Alternative Dosing And Prevention of Transfusions (ADAPT)

Early Phase 1

Active, not recruiting

• Conditions: Sickle Cell Disease
• Interventions: Drug: Hydroxyurea

• Registration Number: NCT05662098
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

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.

Detailed Description

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.

Study Timeline

• Study Start: 2022-06-16
• Study First Submitted: 2022-10-04
• Study First Submitted QC: 2022-12-14
• Study First Posted: 2022-12-22
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-12
• Last Update Posted: 2025-02-14
• Primary Completion: 2026-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (1)

Jinja Regional Referral Hospital (JRRH), Department of Paediatrics, Sickle Cell Clinic; 🇺🇬 Jinja, Uganda