The goal of this study is to evaluate if patients with sickle cell disease can achieve a maximum tolerate dose of hydroxuyrea (HU) over a period of 12 months faster with pharmacokinetic testing than the standard of care bloodwork follow-up. Pharmacokinetic test is used to evaluate the process by which drugs are absorbed, distributed in the body, localized in the tissues, and is excreted.
Patient will be a randomized (coin toss method) into 2 groups. Group A will have an increase of their HU dosage with pharmacokinetic results and Group B will have an increase of their HU dosage following the standard of care bloodwork follow-up.
Group C will include patient with sickle cell disease that has been taking HU for at least 12 months and will undergo a pharmacokinetic dosage to check the level of HU only one time.
Have had confirmed diagnosis of SCD at CHU Sainte-Justine biochemistry lab with hemoglobin electrophoresis.
Patients with SS, SBThal0.
Agree to take hydroxyurea for a period of 12 months
Be between age of 6months old and 18 years old.
Patients with sickle cell genotype other than SS or SBThal0 (SC, SBThal+, SE or SD)
Patients on chronic transfusion program
Patients have received a blood transfusion in the last 4 weeks of study enrollment.
Have received a hematopoietic stem-cell transplantation
Parallel
Pharmacokinetic based dosage change
Diagnostic testThis study will compare 2 groups of sickle cell patients that are receiving hydroxyurea. Group A will have an increase in their dosage based on the pharmacokinetic result over a period of 12 months and Group B will have an increase in their dosage based on the standard of care follow-up over a period of 12 months. The aim is to evaluate if the group A can reach MTD faster than than the Group B
Pharmacokinetic dosing
Diagnostic testPatient with sickle cell disease will undergo one pharmacokinetic test after taking 12 months of hydroxyurea to evaluate HU-AUC at that timepoint
Evaluation of HU-PK at 6 months between group A and group B
Pharmakocinetic dosage of hydroxyurea will be determined at 6 months in group A and group B. The investigator hypothesize that HU-PK in group B may be lower (suboptimal) compared to group A.
Time to reach maximal tolerated dose (MTD)
Time (weeks) to achieve MTD in groups A and B will be determined by evaluating the % of patients reaching MTD (at 3 , 6, 9 and 12 months) in each group. MTD is defined by hematological parameters: Absolute neutrophile count 0.8-1.5x10\*9/L or platelet 80-120x10\*9/L or absolute reticulocyte count 50-80x10\*9/L)
Fetal hemoglobin
Comparing fetal hemoglobin between group A and B
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) in group A and B
Evaluation of the incidence adverse events (AE) and serious adverse events (SAE) in both groups
Evaluation of % of patients reaching AUC of 115 +/- 15mg*h/L at 12 months compared to the percentage of patients in group C reaching the same AUC
Percentage of patients in the HU-AUC (group A) with an AUC of 115 mg\*h/L at 12 months will be compared to the percentage of patients in group C with an AUC of 115 +/-15 mg\*h/L.
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