A Pilot Study of Hydroxyurea for the Treatment of Pulmonary Hypertension in Children and Young Adults With Sickle Cell Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Mean Reduction in TRJV at M6
研究概览
简要总结
The goal of this study is to test the hypothesis that hydroxyurea is effective for the specific treatment of secondary pulmonary hypertension found on screening in children and young adults with sickle cell disease.
详细描述
Increasing evidence suggests that pulmonary hypertension, defined by an elevated tricuspid regurgitant jet velocity (TRJV) on echocardiogram, is a major cause of morbidity and mortality in adults with sickle cell disease (SCD). However, both the prevalence and optimal treatment of pulmonary hypertension in children and young adults with SCD are unknown.
We hypothesize that short term therapy with hydroxyurea will decrease TRJV in children and young adults with pulmonary hypertension found on screening. Patients eligible for treatment will have had evidence of pulmonary hypertension on at least 2 screening echocardiograms. Baseline laboratory tests will be obtained and other causes of secondary pulmonary hypertension will be excluded prior to initiation of treatment. Patients will be treated with hydroxyurea according to a standard dose escalation schedule for a total of 12 months. A clinic visit will be required every 2 months and standard screening for toxicity will be performed monthly. There will be an interim analysis of the primary outcome at 6 months following therapy.
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
- 10 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 10 and 25 years old
- •Sickle cell disease with hemoglobin SS, SC or S-B^0 thalassemia confirmed on hemoglobin electrophoresis
- •Tricuspid regurgitant jet velocity (TRJV) equal to or greater than 2.5 m/sec on 2 baseline Doppler echocardiograms at least 3 months apart
排除标准
- •Patients already being treated with hydroxyurea
- •Patients on a chronic transfusion protocol
- •Patients with evidence of hepatic (alanine aminotransferase [ALT] equal to or greater than 2 SD above normal) or renal dysfunction (creatinine [Cr] equal to or greater than 2 SD above normal)
- •Patients who are pregnant
- •Patients with documented causes of severe pulmonary hypertension other than from SCD
研究组 & 干预措施
Hydroxyurea
Single arm pilot of hydroxyurea in the experimental arm with starting dose of 20 mg/kg/day po and dose escalation every 2 months until maximum tolerated dose.
干预措施: Hydroxyurea (Drug)
结局指标
主要结局
Mean Reduction in TRJV at M6
时间窗: 6 months after initiation of hydroxyurea
Mean Reduction in TRJV at M12
时间窗: 12 months after initiation of hydroxyurea
Tricuspid Regurgitant Jet Velocity
时间窗: 6 and 12 months after HU therapy begins
Primary outcome measure was tricuspid regurgitant jet velocity (TRJV) by echocardiogram after 6 and 12 months of hydroxyurea therapy.
次要结局
- Mean Reduction in Retic% at M6(6 months after initiation of hydroxyurea)
- Mean Reduction in Retic% at M12(12 months after initiation of hydroxyurea)
- Mean Increase Hb F% at M6(6 months after initiation of hydroxyurea)
- Mean Increase in HbF% at M12(12 months after initiation of hydroxyurea)
- Mean Reduction in LDH at M6(6 months after initiation of hydroxyurea)
- Mean Reduction in LDH at M12(12 months after initiation of hydroxyurea)
- Compliance(Throughout study)
研究者
Robert I. Liem
MD, Assistant Professor of Pediatics, NU Feinberg School of Medicine
Ann & Robert H Lurie Children's Hospital of Chicago