Alternative Dosing And Prevention of Transfusions (ADAPT)

Cincinnati Children's Hospital Medical Center

Status and phase: Active, not recruiting; Early Phase 1

Conditions: Sickle Cell Disease

Treatments: Drug: Hydroxyurea

Study type: Interventional

Funder types: Other

Identifiers

NCT05662098

ADAPT

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 12 months to 10 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

Treatment

Experimental group

Description:

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.

Treatment:

Drug: Hydroxyurea