Hydroxyurea Optimization Through Precision Study (HOPS): A Prospective, Multi-center, Randomized Trial of Personalized, Pharmacokinetics-guided Dosing of Hydroxyurea Versus Standard Weight-based Dosing for Children With Sickle Cell Anemia.

Official 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.

Eligibility Requirements

• Minimum Age: 6 Months
• Maximum Age: 21 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: TRIPLE
• Enrollment: 104 participants

Study Arms

• Standard Arm (ACTIVE_COMPARATOR)
  Participants randomized to the standard arm will receive a starting dose of hydroxyurea of 20 mg/kg/day.
• Alternative Arm (EXPERIMENTAL)
  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.

Interventions

• DRUG: Hydroxyurea — The alternative arm will use PK data to choose a starting hydroxyurea dose to achieve an AUC of 115 mg\*h/L to approximate maximum tolerated dose. On the standard arm, participants will start at the traditional, weight-based dose of 20 mg/kg/day. Following selection of the starting dose, all participants will follow the same dose escalation and laboratory monitoring procedures.

Primary Outcomes

• Fetal Hemoglobin (HbF) Response Following Six Months of Hydroxyurea Therapy (6 months after starting daily hydroxyurea therapy)

Secondary Outcomes

• F Cells (Baseline, 6 and 12 months after initiating daily hydroxyurea therapy)
• Gene Expression Patterns of Study Participants (6 Months after initial Hydroxyurea therapy)

Eligibility Criteria

Inclusion Criteria:

* Diagnosis of sickle cell anemia (HbSS, HbSD, HbS/β0-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

Exclusion Criteria:

* Current treatment with chronic, monthly blood transfusions or erythrocytapheresis
* Treatment with hydroxyurea within the past 3 months
* Hemoglobin SC disease, HbS/β+-thalassemia
* Current treatment with other investigational sickle cell medications
* Current known pregnancy or lactation

Trial Locations

• Phoenix Children's Hospital, Phoenix, Arizona, United States
• Children's Healthcare of Atlanta, Atlanta, Georgia, United States
• Children's Hospital of Illinois, Peoria, Illinois, United States
• Carle Foundation Hospital, Urbana, Illinois, United States
• Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, United States
• Indiana Hemophilia & Thrombosis Center, Inc. (IHTC), Indianapolis, Indiana, United States
• Boston Children's Hospital, Boston, Massachusetts, United States
• Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, United States
• Cohen Children's Medical Center/Northwell Health, New Hyde Park, New York, United States
• Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
• ...and 3 more locations

Study Officials

• Patrick Niss, MD — PRINCIPAL_INVESTIGATOR
  Lifespan

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