Optimizing Hydroxyurea Dosage With Pharmakokinetic in Patients Suffering of Moderate to Severe Sickle Cell Anemia

Phase 3Not Yet RecruitingNCT06761560

Yves Pastore29 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Sickle Cell Disease (SCD)

Interventions

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

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria (Group A and B) : * Have had confirmed diagnosis of SCD at CHU Sainte-Justine biochemistry lab with hemoglobin electrophoresis. * Be 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. * Be 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.

Outcomes

Primary Outcomes

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. We hypothesize that HU-PK in group B may be lower (suboptimal) compared to group A.

Time frame: At 6 months

Secondary Outcomes

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)

Time frame: 3, 6, 9 and 12 months

Fetal hemoglobin

Comparing fetal hemoglobin between group A and B

Time frame: at 3, 6 and 12 months

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

Time frame: From enrollment to 12 months

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.

Time frame: At 12 months