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| Name | Class |
|---|---|
| St. Justine's Hospital | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | Patient starting hydroxyurea that will have PK sample procurements at different timpoints over a period of 12 months until HU-AUC shows MTD |
|
| Group B | No Intervention | Patient starting hydroxuyrea that will be followed as per standard of care over a period of 12 months until MTD has been reached | |
| Group C | Experimental | Patient will undergo one PK sample procurement to evaluate level of HU-AUC after 12 months of taking hydroxyurea. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pharmacokinetic based dosage change | Diagnostic Test | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 3, 6, 9 and 12 months |
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Inclusion Criteria (Group A and B) :
Inclusion Criteria (Group C) :
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yves Pastore, MD | Contact | 514-345-4931 | 5027 | yves.pastore.med@ssss.gouv.qc.ca |
| Bianka Courcelle, Research nurse, RN | Contact | 514-345-4931 | 3757 | bianka.courcelle.hsj@ssss.gouv.qc.ca |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Sainte-Justine | Montreal | Quebec | H3T 1C5 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19797523 | Background | Verduzco LA, Nathan DG. Sickle cell disease and stroke. Blood. 2009 Dec 10;114(25):5117-25. doi: 10.1182/blood-2009-05-220921. | |
| 29803275 | Background | Meier ER. Treatment Options for Sickle Cell Disease. Pediatr Clin North Am. 2018 Jun;65(3):427-443. doi: 10.1016/j.pcl.2018.01.005. |
| Label | URL |
|---|---|
| Related Info | View source |
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This is a pilot study with a small group of participant.
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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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
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|
| Pharmacokinetic dosing | Diagnostic Test | Patient with sickle cell disease will undergo one pharmacokinetic test after taking 12 months of hydroxyurea to evaluate HU-AUC at that timepoint |
|
| Fetal hemoglobin | Comparing fetal hemoglobin between group A and B | 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 | 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. | At 12 months |
| 31106898 | Background | McGann PT, Niss O, Dong M, Marahatta A, Howard TA, Mizuno T, Lane A, Kalfa TA, Malik P, Quinn CT, Ware RE, Vinks AA. Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia. Am J Hematol. 2019 Aug;94(8):871-879. doi: 10.1002/ajh.25510. Epub 2019 Jun 12. |
| 32869281 | Background | Dong M, McGann PT. Changing the Clinical Paradigm of Hydroxyurea Treatment for Sickle Cell Anemia Through Precision Medicine. Clin Pharmacol Ther. 2021 Jan;109(1):73-81. doi: 10.1002/cpt.2028. Epub 2020 Oct 8. |
| 28847416 | Background | Marahatta A, Ware RE. Hydroxyurea: Analytical techniques and quantitative analysis. Blood Cells Mol Dis. 2017 Sep;67:135-142. doi: 10.1016/j.bcmd.2017.08.009. Epub 2017 Aug 8. |
| 28131939 | Background | Hai X, Guo M, Gao C, Zhou J. Quantification of hydroxyurea in human plasma by HPLC-MS/MS and its application to pharmacokinetics in patients with chronic myeloid leukaemia. J Pharm Biomed Anal. 2017 Apr 15;137:213-219. doi: 10.1016/j.jpba.2017.01.008. Epub 2017 Jan 10. |
| 21571150 | Background | Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW; BABY HUG investigators. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011 May 14;377(9778):1663-72. doi: 10.1016/S0140-6736(11)60355-3. |
| 22915643 | Background | Thornburg CD, Files BA, Luo Z, Miller ST, Kalpatthi R, Iyer R, Seaman P, Lebensburger J, Alvarez O, Thompson B, Ware RE, Wang WC; BABY HUG Investigators. Impact of hydroxyurea on clinical events in the BABY HUG trial. Blood. 2012 Nov 22;120(22):4304-10; quiz 4448. doi: 10.1182/blood-2012-03-419879. Epub 2012 Aug 22. |
| 30206297 | Background | Yahouedehou SCMA, Adorno EV, da Guarda CC, Ndidi US, Carvalho SP, Santiago RP, Aleluia MM, de Oliveira RM, Goncalves MS. Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism. Pharmacogenomics J. 2018 Dec;18(6):730-739. doi: 10.1038/s41397-018-0045-1. Epub 2018 Sep 12. |
| 16713922 | Background | Switzer JA, Hess DC, Nichols FT, Adams RJ. Pathophysiology and treatment of stroke in sickle-cell disease: present and future. Lancet Neurol. 2006 Jun;5(6):501-12. doi: 10.1016/S1474-4422(06)70469-0. |
| 24237976 | Background | Quinn CT. Sickle cell disease in childhood: from newborn screening through transition to adult medical care. Pediatr Clin North Am. 2013 Dec;60(6):1363-81. doi: 10.1016/j.pcl.2013.09.006. |
| 24589261 | Background | Hebbel RP. Ischemia-reperfusion injury in sickle cell anemia: relationship to acute chest syndrome, endothelial dysfunction, arterial vasculopathy, and inflammatory pain. Hematol Oncol Clin North Am. 2014 Apr;28(2):181-98. doi: 10.1016/j.hoc.2013.11.005. |
| 24589260 | Background | Kuypers FA. Hemoglobin s polymerization and red cell membrane changes. Hematol Oncol Clin North Am. 2014 Apr;28(2):155-79. doi: 10.1016/j.hoc.2013.12.002. Epub 2014 Jan 22. |
| 25390139 | Background | Pleasants S. Epidemiology: a moving target. Nature. 2014 Nov 13;515(7526):S2-3. doi: 10.1038/515S2a. No abstract available. |
| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |