Back to resultsAlternative Dosing And Prevention of Transfusions (ADAPT)
Primary Purpose
Sickle Cell Disease
Status
Recruiting
Phase
Early Phase 1
Locations
Uganda
Study Type
Interventional
Intervention
Hydroxyurea
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring Pharmacokinetics, Hydroxyurea, Transfusion
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
Sites / Locations
- Jinja Regional Referral Hospital (JRRH), Department of Paediatrics, Sickle Cell ClinicRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment
Arm 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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT05662098
First Posted
October 4, 2022
Last Updated
December 14, 2022
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Jinja Regional Referral Hospital (JRRH), Sickle Cell Clinic, Jinja, Uganda
1. Study Identification
Unique Protocol Identification Number
NCT05662098
Brief Title
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
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 16, 2022 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
January 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Jinja Regional Referral Hospital (JRRH), Sickle Cell Clinic, Jinja, Uganda
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
Pharmacokinetics, Hydroxyurea, Transfusion
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Hydroxyurea
Intervention 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.
Primary Outcome Measure Information:
Title
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
Description
The incidence rate ratio of transfusions overall and by specific indication during the screening phase as compared to the treatment phase
Time Frame
One year (Enrollment - Month 15)
Secondary Outcome Measure Information:
Title
To determine clinical and laboratory factors associated with reduction in blood transfusions for children with SCA on hydroxyurea treatment
Description
The relative risk of transfusion due to the most common clinical diagnoses and laboratory factors for children with SCA on hydroxyurea treatment.
Time Frame
One year (Enrollment - Month 15)
Other Pre-specified Outcome Measures:
Title
To assess the feasibility and safety of a pharmacokinetic (PK)-based hydroxyurea dose within the predicted treatment range for Uganda
Description
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.
Time Frame
One year (Enrollment - Month 15)
Title
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
Description
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.
Time Frame
One year (Enrollment - Month 15)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Russell Ware, MD, PhD
Phone
(513) 803-1108
Email
russell.ware@cchmc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Teresa Latham, M.A., LPCC-S
Phone
(513) 803-7922
Email
teresa.latham@cchmc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Russell Ware, MD, PhD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Study Director
Facility Information:
Facility Name
Jinja Regional Referral Hospital (JRRH), Department of Paediatrics, Sickle Cell Clinic
City
Jinja
Country
Uganda
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert O. Opoka, MB ChB, PhD
12. IPD Sharing Statement
Learn more about this trial
Alternative Dosing And Prevention of Transfusions (ADAPT)
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