Sickle Cell Disease
Conditions
Keywords
Hydroxyurea, Transfusion
Brief summary
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
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.
Interventions
DRUGHydroxyurea
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.
Sponsors
Children's National Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, single arm, open label study of combination hydroxyurea and simple chronic transfusion.
Eligibility
Sex/Gender
ALL
Age
2 Years to 24 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of SCA (Hb SS or Sβ0 thalassemia). 2. 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
1. 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. 2. Treatment with hydroxyurea in the 12 months prior to study enrollment. 3. Abnormal initial laboratory values (temporary exclusions): 1. Absolute neutrophil count \<1.5 x 10\^9/L 2. Platelet count \<100 x 10\^9/L 3. Serum creatinine more than twice upper limit for age 4. Pregnancy or unwillingness to use a medically acceptable form of contraception if sexually active.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment ratio | 1 year | number of participants who enroll on the study / total number of eligible subjects |
| Retention ratio | 1 year | number participants who remain on study 1 year after HAT target dose / total number enrolled participants |
| Hydroxyurea adherence ratio | 1 year | (hydroxyurea amount dispensed - amount returned) / prescribed amount between visits |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects who develop an hemoglobin (Hb) S >45% AND an Hb >11.0 g/dL | 1 year | incidence of above safety event will be monitored closely throughout the trial |
| Volume of red blood cells transfused per patient weight | 1 year | measure to evaluate the transfusion requirement of HAT |
Countries
United States
Outcome results
None listed