Alternative Dosing And Prevention of Transfusions (ADAPT)

NCT05662098 | Active Not Recruiting Early Phase 1

• 1 other identifier: ADAPT
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Keywords

Pharmacokinetics; Hydroxyurea; Transfusion

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• To determine clinical and laboratory factors associated with reduction in blood transfusions for children with SCA on hydroxyurea treatment

  One year (Enrollment - Month 15)

Other Outcomes (2)

• 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)

• 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)

Study Arms (1)

Treatment

EXPERIMENTAL

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

Interventions

Hydroxyurea DRUG

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

Eligibility Criteria

• Age: 12 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Current hydroxyurea treatment (or within the past 6 months)
• Regular blood transfusions (6 or more within the past 12 months)
• 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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Jinja Regional Referral Hospital (JRRH), Sickle Cell Clinic, Jinja, Uganda: collaborator

Study Sites (1)

Jinja Regional Referral Hospital (JRRH), Department of Paediatrics, Sickle Cell Clinic

Jinja, Uganda

Location

Related Publications (2)

• Power-Hays A, Namazzi R, Dong M, Kazinga C, Kato C, Aliwuya S, McElhinney K, Conroy AL, Lane A, John C, Vinks AA, Latham T, Opoka RO, Ware RE. The feasibility of pharmacokinetic-based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial. Br J Clin Pharmacol. 2025 Jun;91(6):1865-1872. doi: 10.1111/bcp.70071.

  PMID: 40441700 DERIVED

• Power-Hays A, Namazzi R, Dong M, Kazinga C, Kato C, Aliwuya S, McElhinney K, Conroy AL, Lane A, John C, Vinks AA, Latham T, Opoka RO, Ware RE. The feasibility of pharmacokinetic-based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial. Br J Clin Pharmacol. 2025 Apr 13;91(6):1865-72. doi: 10.1002/bcp.70071. Online ahead of print.

  PMID: 40222814 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Russell Ware, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 4, 2022
• First Posted: December 22, 2022
• Study Start: June 16, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

UG (1)