Hydroxyurea Optimization Through Precision Study (HOPS)

Lifespan

Status and phase: Completed; Phase 3

Conditions: Sickle Cell Anemia; Sickle Cell Disease

Treatments: Drug: Hydroxyurea

Study type: Interventional

Funder types: Other

Identifiers

NCT03789591

CCHMC_HOPS

Details and patient eligibility

About

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.

Full 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.

Enrollment: 104 patients

Sex: All

Ages: 6 months to 21 years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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104 participants in 2 patient groups

Standard Arm

Active Comparator group

Description:

Participants randomized to the standard arm will receive a starting dose of hydroxyurea of 20 mg/kg/day.

Treatment:

Drug: Hydroxyurea

Alternative Arm

Experimental group

Description:

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.

Treatment:

Drug: Hydroxyurea