Hydroxyurea Optimization Through Precision Study
- Registration Number
- NCT03789591
- Lead Sponsor
- Children's Hospital Medical Center, Cincinnati
- Brief Summary
Hydroxyurea Optimization through Precision Study (HOPS) is a prospective, multi-center, randomized trial that will directly compare a novel, individualized dosing strategy of hydroxyurea to standard weight-based dosing for children with SCA. The primary objective of the study is to evaluate whether a pharmacokinetics-based starting hydroxyurea dose thieves superior fetal hemoglobin response to to standard weight-based initial dosing. Patients will be recruited from the pediatric sickle cell clinic at Cincinnati Children's Hospital Medical Center and from additional pediatric sickle cell centers within the United States.
- Detailed Description
The trial will recruit patients who have decided to initiate hydroxyurea therapy. All participants will have pharmacokinetics studies performed at baseline, following a 20 mg/kg oral dose of hydroxyurea. Pharmacokinetic sampling will use a sparse sampling approach, requiring collection of blood at 3 time points (15 minutes, 60 minutes, 180 minutes) following the hydroxyurea dose. Enrolled participants will be randomized to receive either hydroxyurea using a starting dose of 20 mg/kg/day (Standard Arm) or a personalized PK-guided dose (Alternative Arm) to target an area under the curve (AUC) of 115 mg\*h/L based to approximate hydroxyurea exposure seen when patients are escalated to maximum tolerated dose (MTD).
Following randomization and selection of the initial dose, participants in both arms will follow the same procedures of laboratory medication holds for hematological toxicity. The primary endpoint is fetal hemoglobin (HbF) six months following the initiation of hydroxyurea therapy with the hypothesis that participants starting with a PK-guided dose will achieve HbF at least 5% greater than those starting with a 20 mg/kg dose. Based upon the estimated number of new hydroxyurea starts at each site, it is anticipated that it will take 24 months to enroll the 116 participants required to achieve sufficient power to assess the primary endpoint. The study will conclude for each participant 12 months following hydroxyurea initiation.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 116
- Diagnosis of sickle cell anemia (HbSS, HbSD, HbS/ฮฒ0-thalassemia, or similarly severe SCA genotype)
- Age 6 months to 21 years at the time of enrollment
- Clinical decision by patient, family, and healthcare providers to initiate hydroxyurea therapy
- Current treatment with chronic, monthly blood transfusions or erythrocytapheresis
- Treatment with hydroxyurea within the past 3 months
- Hemoglobin SC disease, HbS/ฮฒ+-thalassemia
- Current treatment with other investigational sickle cell medications
- Current known pregnancy or lactation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard Arm Hydroxyurea Participants randomized to the standard arm will receive a starting dose of hydroxyurea of 20 mg/kg/day. Alternative Arm Hydroxyurea Participants randomized to the alternative arm will receive a pharmacokinetic guided starting dose of hydroxyurea based on PK labs drawn at a baseline visit to target an area under the curve (AUC) of 115 mg\*h/L in an attempt to approximate maximum tolerated dose (MTD). This dose will not exceed the maximum tolerated dose of 35 mg/kg/day.
- Primary Outcome Measures
Name Time Method Fetal Hemoglobin (HbF) Response Following Six Months of Hydroxyurea Therapy 6 months after starting daily hydroxyurea therapy The primary outcome will be HbF response six months after starting hydroxyurea therapy with the hypothesis that participants in the Alternative Arm (PK-guided starting dose) will have at least 5% higher HbF than the Standard Arm (20 mg/kg starting dose)
- Secondary Outcome Measures
Name Time Method Gene Expression Patterns of Study Participants 6 Months after initial Hydroxyurea therapy The epigenomic signature and gene expression patterns of study participants receiving hydroxyurea therapy at MTD. MTD is defined as a stable dose without any dose increases (except to account for weight gain), holds, or decreases within 8 weeks with laboratory criteria within the target range. This outcome will explain the mechanisms that yield high HbF responses.
F Cells Baseline, 6 and 12 months after initiating daily hydroxyurea therapy In addition to traditional %HbF measurement, F cells will be measured at baseline, 6 months, and 12 months
Trial Locations
- Locations (14)
Boston Children's Hospital
๐บ๐ธBoston, Massachusetts, United States
Cleveland Clinic Children's
๐บ๐ธCleveland, Ohio, United States
Carle Foundation Hospital
๐บ๐ธUrbana, Illinois, United States
Riley Hospital for Children at Indiana University Health
๐บ๐ธIndianapolis, Indiana, United States
Children's Hospital of Illinois
๐บ๐ธPeoria, Illinois, United States
Phoenix Children's Hospital
๐บ๐ธPhoenix, Arizona, United States
Indiana Hemophilia & Thrombosis Center, Inc. (IHTC)
๐บ๐ธIndianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center
๐บ๐ธCincinnati, Ohio, United States
Rainbow Babies / University Hospitals Cleveland Medical Center
๐บ๐ธCleveland, Ohio, United States
Nationwide Children's Hospital.
๐บ๐ธColumbus, Ohio, United States
Children's Hospital of Wisconsin
๐บ๐ธMilwaukee, Wisconsin, United States
Cohen Children's Medical Center/Northwell Health
๐บ๐ธNew Hyde Park, New York, United States
Children's Healthcare of Atlanta
๐บ๐ธAtlanta, Georgia, United States
Children's Hospitals and Clinics of Minnesota
๐บ๐ธMinneapolis, Minnesota, United States