Alternative Dosing And Prevention of Transfusions (ADAPT): A Prospective Study to Reduce Transfusion Requirements for Children With Sickle Cell Anemia Using Pharmacokinetics-based Hydroxyurea Dosing
试验速览
- 阶段
- 早期 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- To compare the rates of blood transfusions overall and by specific indications in children with sickle cell anaemia (SCA), prior to and during hydroxyurea treatment
研究概览
简要总结
ADAPT is a prospective cohort study at Jinja Regional Referral Hospital (JRRH) primarily to assess the effect of hydroxyurea on blood transfusion utilization and secondarily to determine the feasibility of PK-guided hydroxyurea dosing.
详细描述
Hypothesis
- There will be a 50% reduction in the rate of blood transfusions received during the hydroxyurea treatment period compared with the pre-treatment period.
- A PK-guided starting dose will be generated for 80% of participants.
- Participants on PK-guided hydroxyurea treatment will require 25% fewer blood transfusions during their first year of hydroxyurea than those on dose escalation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Months 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with documented HbSS disease
- •Age: ≥ 12 months and ≤ 10 years of age, at the time of enrollment
- •Parent or guardian willing and able to provide informed consent
- •Able to comply with all study related treatments, evaluations, and follow-up
排除标准
- •Current hydroxyurea treatment (or within the past 6 months)
- •Regular blood transfusions (6 or more within the past 12 months)
- •Transfusion within the last 30 days (temporary exclusion)
- •Known malignancy or other known chronic illnesses including but not limited to active tuberculosis, renal disease
- •Current participation in other therapeutic clinical trials, or within 6 months of prior disease-modifying treatments
研究组 & 干预措施
Treatment
All participants will receive an individualized PK hydroxyurea assessment. Participants for whom the PK-process successfully generates a dose in the predicted treatment range of 15-35 mg/kg/day, will start on that personalized dose. Participants for whom the process does not generate a starting hydroxyurea dose in the predicted treatment range, due to potential pitfalls in lab draws, serum storage, sample processing, or hydroxyurea analysis, will start at a default dose of 20.0 ± 2.5 mg/kg/day. For all participants, the hydroxyurea dose will be adjusted as needed based on blood counts to establish the optimal dose. Where necessary, a weekly dosing average will be determined, so that treatment can occur solely with locally available and affordable 500mg hydroxyurea capsules.
干预措施: Hydroxyurea (Drug)
结局指标
主要结局
To compare the rates of blood transfusions overall and by specific indications in children with sickle cell anaemia (SCA), prior to and during hydroxyurea treatment
时间窗: One year (Enrollment - Month 15)
The incidence rate ratio of transfusions overall and by specific indication during the screening phase as compared to the treatment phase
次要结局
- To determine clinical and laboratory factors associated with reduction in blood transfusions for children with SCA on hydroxyurea treatment(One year (Enrollment - Month 15))