Alternative Dosing And Prevention of Transfusions (ADAPT)

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05662098
• Other study ID #: ADAPT
• Status: Recruiting
• Phase: Early Phase 1
• Start date: June 16, 2022
• Est. completion date: December 31, 2027

Study information

• Verified date: January 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Russell Ware, MD, PhD
• Phone: (513) 803-1108
• Email: russell.ware[@]cchmc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months to 10 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

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.

Locations

Country	Name	City	State
Uganda	Jinja Regional Referral Hospital (JRRH), Department of Paediatrics, Sickle Cell Clinic	Jinja

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Jinja Regional Referral Hospital (JRRH), Sickle Cell Clinic, Jinja, Uganda

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To assess the feasibility and safety of a pharmacokinetic (PK)-based hydroxyurea dose within the predicted treatment range for Uganda	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.	One year (Enrollment - Month 15)
Other	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	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.	One year (Enrollment - Month 15)
Primary	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	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)