Hydroxyurea and Transfusion

Study Overview
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Brief Summary
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This study will prospectively investigate the feasibility, safety, and transfusion requirements of adding hydroxyurea to simple chronic transfusions for patients with sickle cell anemia already on chronic transfusions.

Detailed Description
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This is a single-arm, prospective study of hydroxyurea added to simple chronic transfusions, combination treatment termed hydroxyurea and transfusion (HAT). The primary objective of the study is to determine the feasibility of HAT for patients with sickle cell anemia (SCA) currently being treated only with simple transfusions for stroke prevention. Secondary objectives include: to evaluate the safety of HAT and to determine if HAT decreases transfusion requirements in this patient population. Exploratory objectives include: to evaluate with HAT changes in pre-transfusion laboratories and biomarkers of cerebrovascular disease progression, and to describe changes on brain imaging.

Official Title
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Hydroxyurea and Transfusion: Pilot Study of Combination Therapy for Patients With Sickle Cell Anemia

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Hydroxyurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of SCA (Hb SS or Sβ0 thalassemia). On simple chronic transfusion therapy for stroke prevention (primary or secondary prevention) for ≥1 year with no plans to stop simple chronic transfusion in the next year. Exclusion Criteria: Poor adherence to simple transfusion regimen as defined by having an HbS >45% at any time in the last year AND a transfusion interval >5 weeks. Treatment with hydroxyurea in the 12 months prior to study enrollment. Abnormal initial laboratory values (temporary exclusions): Absolute neutrophil count <1.5 x 10^9/L Platelet count <100 x 10^9/L Serum creatinine more than twice upper limit for age Pregnancy or unwillingness to use a medically acceptable form of contraception if sexually active.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective, single arm, open label study of combination hydroxyurea and simple chronic transfusion.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxyurea and Transfusion (HAT)<br>Combination hydroxyurea and simple chronic transfusion therapy | Drug: Hydroxyurea<br>* Participants will be started on hydroxyurea 20 ± 2.5 mg/kg/day in addition to continuing simple chronic transfusion every 4 weeks ± 1 week. Hydroxyurea will be dose escalated to achieve a HAT target dose (HAT-TD). Hydroxyurea will be increased by 5 mg/kg/day after 8 weeks of a dose if HAT-TD is not achieved (maximum daily dose 2,000 mg). After HAT-TD has been achieved, minor dose increases may occur if subject grows a significant amount to maintain the same mg/kg dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment ratio | number of participants who enroll on the study / total number of eligible subjects | 1 year | 
| Retention ratio | number participants who remain on study 1 year after HAT target dose / total number enrolled participants | 1 year | 
| Hydroxyurea adherence ratio | (hydroxyurea amount dispensed - amount returned) / prescribed amount between visits | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who develop an hemoglobin (Hb) S >45% AND an Hb >11.0 g/dL | incidence of above safety event will be monitored closely throughout the trial | 1 year | 
| Volume of red blood cells transfused per patient weight | measure to evaluate the transfusion requirement of HAT | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydroxyurea, Transfusion