Clinical trial NCT03789591: Hydroxyurea Optimization Through Precision Study
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sickle Cell Disease
Sickle Cell Anemia
Keywords: Hydroxyurea
HbSS
HbSD
TREAT
Lead sponsor: Lifespan
Sponsor class: OTHER
Collaborators: name: Doris Duke Charitable Foundation
First posted: 2018-12-28
Enrollment: 104
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Fetal Hemoglobin (HbF) Response Following Six Months of Hydroxyurea Therapy
timeFrame: 6 months after starting daily hydroxyurea therapy
Secondary outcomes:
measure: F Cells
timeFrame: Baseline, 6 and 12 months after initiating daily hydroxyurea therapy
measure: Gene Expression Patterns of Study Participants
timeFrame: 6 Months after initial Hydroxyurea therapy
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Peoria
country: United States
facility: Children's Hospital of Illinois
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Hemophilia & Thrombosis Center, Inc. (IHTC)
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center/Northwell Health
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies / University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital.
state: Ohio
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Lifespan
name: Patrick Niss, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.