Hydroxyurea Optimization Through Precision Study
| Status: | Recruiting |
|---|---|
| Conditions: | Anemia, Anemia |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | Any - 21 |
| Updated: | 3/23/2019 |
| Start Date: | January 17, 2019 |
| End Date: | December 31, 2021 |
| Contact: | Amanda Pfeiffer |
| Email: | Amanda.Pfeiffer@cchmc.org |
| Phone: | 513-803-4977 |
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.
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.
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.
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.
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.
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
We found this trial at
1
site
3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
Cincinnati, Ohio 45229
1-513-636-4200
Principal Investigator: Patrick T McGann, MD
Phone: 513-803-4977
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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