Clinical trial NCT05662098: Alternative Dosing And Prevention of Transfusions (ADAPT)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Sickle Cell Disease
Keywords: Pharmacokinetics
Hydroxyurea
Transfusion
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Jinja Regional Referral Hospital (JRRH), Sickle Cell Clinic, Jinja, Uganda
First posted: 2022-12-22
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: One year (Enrollment - Month 15)
Secondary outcomes:
measure: To determine clinical and laboratory factors associated with reduction in blood transfusions for children with SCA on hydroxyurea treatment
timeFrame: One year (Enrollment - Month 15)
Other outcomes:
measure: To assess the feasibility and safety of a pharmacokinetic (PK)-based hydroxyurea dose within the predicted treatment range for Uganda
timeFrame: One year (Enrollment - Month 15)
measure: 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
timeFrame: One year (Enrollment - Month 15)
Locations:
city: Jinja
country: Uganda
facility: Jinja Regional Referral Hospital (JRRH), Department of Paediatrics, Sickle Cell Clinic
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Russell Ware, MD, PhD
role: STUDY_DIRECTOR
References: