N-Acetylcysteine in Patients With Sickle Cell Disease - Reducing the Incidence of Daily Life Pain
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 11
- 主要终点
- The incidence rate of SCD related pain in daily life per patient year
研究概览
简要总结
The primary aim of this study is to evaluate the effect of the drug N-Acetylcysteine on the frequency of pain in daily life in patients with Sickle Cell Disease (SCD).
Pain is an invalidating hallmark of this disease and has a considerable impact on the Quality of Life of patients and the medical health care system. Oxidative stress is hypothesized to play a central role in its pathophysiology. In pilot studies the administration of N-Acetylcysteine (NAC) resulted in a reduction of oxidative stress. Moreover, administration of NAC seemed to decrease hospitalization for painful crises in a small pilot study in patients with SCD.
This study will be performed as a multicenter, randomized, controlled trial where patients will be treated with either NAC or placebo for a period of 6 months. The investigators expect that NAC can reduce the frequency of pain in patients with SCD, thereby improving their quality of life and participation in society.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 12 years or older
- •Sickle cell disease, either homozygous sickle cell disease (HbSS), compound heterozygous sickle cell disease (HbSC), HbSβ0 or HbSβ+ thalassemia
- •History of at least 1.0 painful crisis per year in the past 3 years (visit to medical facility is not required)
排除标准
- •Chronic blood transfusion or transfusion in the preceding 3 months
- •Painful crisis in the last 4 weeks (with respect to the moment of inclusion)
- •Pregnancy, breast feeding or the desire to get pregnant in the following 7 months
- •Known active gastric/duodenal ulcers
- •Hydroxycarbamide (HC) treatment with unstable dose in the last 3 months or started on HC shorter then 6 months prior to study
- •Known poor compliance in earlier trials regarding the completion of pain diaries
- •Insufficient compliance in run-in period
- •Known hypersensitivity to acetylcysteine or one of the other components of the study medication
- •Use of pain medication for sickle-cell related pains on more than 15 days per month in the past 6 months ('chronic pain').
研究组 & 干预措施
N-Acetylcysteine
N-Acetylcysteine 600mg 1 oral tablet twice daily during 6 months
干预措施: N-Acetylcysteine (Drug)
Placebo
Placebo 1 oral tablet twice daily during 6 months
干预措施: Placebo (Drug)
结局指标
主要结局
The incidence rate of SCD related pain in daily life per patient year
时间窗: 6 months
The incidence of pain in daily life will be expressed as the number of pain days in relation to total follow-up time, and transformed to an event rate per patient year with a corresponding rate ratio and its 95% confidence interval. A pain day will be defined as: * When the box "Yes, I have experienced pain" is checked in the daily pain diary. * Days with hospital admission for painful crisis will be included in the total number of pain days and in the total number of diary observation days, irrespective of pain diary reports on these dates.
次要结局
- The severity of SCD related pain in daily life, using a 0-10 numerical rating scale (NRS) in the study pain diary.(6 months)
- The changes in blood markers of oxidative stress, hemolysis, hypercoagulability, inflammation, erythrocyte adhesion and endothelial dysfunction(6 months)
- Time in days to first painful crisis (as defined above)(6 months)
- Time in days to first hospital admission for painful crisis (as defined above)(6 months)
- Compliance of study medication; N-acetylcysteine plasma concentrations(6 months)
- The incidence rate per patient year of use of home pain medication (based on pain diary observation). This information will be recorded by subjects in their daily pain diary, including type and dosage of pain medication.(6 months)
- The incidence rate per patient year of painful crises (episodes, based on pain diary observation)(6 months)
- The incidence rate per patient year of days with painful crises (days, based on pain diary observation)(6 months)
- The severity of painful crises. This will be defined using a 0-10 numerical rating scale (NRS) in the pain diary.(6 months)
- The incidence rate per patient year of hospital admissions(6 months)
- The tolerability of NAC, defined as the number of participants with adverse events.(6 months)
- Incidence of SCD complications.(6 months)
- Compliance of study medication; proportion of study medication used based on pill counts.(6 months)
- The incidence rate per patient year of hospital admission days(6 months)
- The health-related Quality of Life, as measured by use of validated questionnaires.(6 months)
- The SCD-related societal costs, assessed by a prospective cost-effectiveness analysis(6 months)
研究者
B.J. Biemond
dr.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)