Sickle Cell Disease (SCD)
Conditions
Keywords
hydroxyurea, pharmacokinetic, sickle cell disease
Brief summary
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.
Interventions
DIAGNOSTIC_TESTPharmacokinetic based dosage change
This 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
DIAGNOSTIC_TESTPharmacokinetic dosing
Patient with sickle cell disease will undergo one pharmacokinetic test after taking 12 months of hydroxyurea to evaluate HU-AUC at that timepoint
Sponsors
Yves Pastore
St. Justine's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Group A will receive dosing of hydroxyurea depending on the HU-AUC result at different timepoint until MTD Group B will receive dosing of hydroxyurea following the standard of care bloodwork follow-up until MTD Group C will undergo one pharmacokinetic testing after taking hydroxyurea for at least 12 months
Eligibility
Sex/Gender
ALL
Age
6 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
(Group A and B) : * 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. * Have consented for participation in the study. Inclusion Criteria (Group C) : * Have had confirmed diagnosis of SCD at CHU Sainte-Justine biochemistry lab with hemoglobin electrophoresis. * Patients with SS, SBThal0. * Have taken hydroxyurea for a period of at least 12 months, and have received HU at a stable dose and at MTD for at least 6 months. * Be between age of 6months old and 18 years old. * Have consented for participation in the study.
Exclusion criteria
* 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 * Creatinine \>2x normal for age * ALT\>2x normal for age * Sexually active females unwilling to comply with reliable method of birth control * Pregnancy * Conditions which in the opinion of the investigator, would compromise participation in the study will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of HU-PK at 6 months between group A and group B | At 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to reach maximal tolerated dose (MTD) | 3, 6, 9 and 12 months | 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 | at 3, 6 and 12 months | Comparing fetal hemoglobin between group A and B |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) in group A and B | From enrollment to 12 months | 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 | At 12 months | 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. |
Countries
Canada
Contacts
CONTACTYves Pastore, MD
CONTACTBianka Courcelle, Research nurse, RN
Outcome results
None listed