Hydroxyurea Optimization Through Precision Study

NCT ID: NCT03789591

Last Updated: 2025-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-17
• Study Completion Date: 2025-03-19

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.

Conditions

Sickle Cell Disease; Sickle Cell Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Standard Arm

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

Group Type: ACTIVE_COMPARATOR

Hydroxyurea

Intervention Type: DRUG

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.

Alternative Arm

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.

Group Type: EXPERIMENTAL

Hydroxyurea

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Doris Duke Charitable Foundation

OTHER

Sponsor Role: collaborator

Lifespan

OTHER

Sponsor Role: lead

Responsible Party

Patrick McGann

Director, Brown University Health Comprehensive Sickle Cell Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrick Niss, MD

Role: PRINCIPAL_INVESTIGATOR

Lifespan

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

Rainbow Babies / University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Nationwide Children's Hospital.

Columbus, Ohio, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Meier ER, Creary SE, Heeney MM, Dong M, Appiah-Kubi AO, Nelson SC, Niss O, Piccone C, Quarmyne MO, Quinn CT, Saving KL, Scott JP, Talati R, Latham TS, Pfeiffer A, Shook LM, Vinks AA, Lane A, McGann PT. Hydroxyurea Optimization through Precision Study (HOPS): study protocol for a randomized, multicenter trial in children with sickle cell anemia. Trials. 2020 Nov 27;21(1):983. doi: 10.1186/s13063-020-04912-z.

Reference Type: DERIVED

PMID: 33246482 (View on PubMed)

Other Identifiers

CCHMC_HOPS

Identifier Type: -

Identifier Source: org_study_id