A Multicenter, Double-blind, Randomized, Placebo and Active-controlled Study of Pregabalin for the Treatment of Uremic Pruritus
试验速览
- 阶段
- 4 期
- 入组人数
- 210
- 试验地点
- 1
- 主要终点
- The changes in pruritus symptoms assessed by VAS
研究概览
简要总结
Pruritus s a very distressing problem affecting patients with uremia and the prevalence of uremic pruritus (UP) ranges between 22% to 66%. Although some studies suggested pruritus is being decreased recently by use of better dialysis techniques, accumulating studies have shown the still high prevalence of UP. Because of its long duration, frequency and high intensity, UP has been reported to have a negative impact upon the patients' quality of life (QoL). However, the therapies in use, including antihistamines, ultraviolets, opioid antagonists and topical agents, are generally of insufficient efficacy, failing to provide adequate and long-lasting relief. Based on the neuropathic hypothesis and frequent co-occurrence of chronic pruritus and peripheral neuropathy in the patients undergoing hemodialysis, gabapentin, a medication widely used for a spectrum of neuropathic pain syndromes, has recently been suggested to be effective in the treatment of UP.Pregabalin, another gabaergic drug structurally related to gabapentin, have an advantage over gabapentin in terms of its more rapid response to stressful symptoms. Only two very recently small-scaled studies evaluate the effect of pregabalin for UP. However, both these studies were not randomized, placebo-controlled trails.As UP is still one of the most vexing and disabling symptoms in patients with ESRD, we decided to do this multicenter, randomized double-blind placebo-controlled trial (RCT) with a larger sample size and a longer duration.
详细描述
Pruritus s a very distressing problem affecting patients with uremia and the prevalence of uremic pruritus (UP) ranges between 22% to 66%. Although some studies suggested pruritus is being decreased recently by use of better dialysis techniques, accumulating studies have shown the still high prevalence of UP. Because of its long duration, frequency and high intensity, UP has been reported to have a negative impact upon the patients' quality of life (QoL). However, the therapies in use, including antihistamines, ultraviolets, opioid antagonists and topical agents, are generally of insufficient efficacy, failing to provide adequate and long-lasting relief. Based on the neuropathic hypothesis and frequent co-occurrence of chronic pruritus and peripheral neuropathy in the patients undergoing hemodialysis, gabapentin, a medication widely used for a spectrum of neuropathic pain syndromes, has recently been suggested to be effective in the treatment of UP.
Pregabalin, another gabaergic drug structurally related to gabapentin, have an advantage over gabapentin in terms of its more rapid response to stressful symptoms. Only two very recently small-scaled studies evaluate the effect of pregabalin for UP. However, both these studies were not randomized, placebo-controlled trails.
Studies focusing on the treatment of UP were limited and no studies comparing the efficacy between pregabalin and antihistamine, most widely used for the therapy of UP currently, were conducted. Additionally. there were few studies investigating the effect of the drugs used for UP on the QoL outcomes, though UP has a great impact on the patients' QoL. As UP is still one of the most vexing and disabling symptoms in patients with ESRD, we decided to do this multicenter, randomized double-blind placebo-controlled trial (RCT) with a larger sample size and a longer duration.
Objectives:
To investigate the efficacy and the safety of pregabalin, as compared with fexofenadine and placebo, in the treatment of uremic pruritus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients who have end-stage renal disease (ESRD) on maintenance hemodialysis more than twice weekly for at least three months and suffered from uremic pruritus.
- •20 Years and older
- •Definition of uremic pruritus:
- •Patients were considered to have pruritus if they had either of the following conditions:
- •at least 3 episodes of itch during a period of 2 weeks or less, with the symptom appearing a few times a day, lasting at least a few minutes, and troubling the patient
- •he appearance of an itch in a regular pattern during a period of 6 months, but less frequently than listed above.
- •To be defined as "uremic," the pruritus had to appear shortly before the onset of dialysis, or at any time after that, without evidence of any other active disease that could explain the pruritus.
- •Patients who suffer from severe pruritus unresponsive to topical emollient and corticosteroids, and were diagnosed as having uremic pruritus by dermatologists
排除标准
- •All patients with pruritus attributable to any other causes, such as scabies or other evident skin diseases (atopic dermatitis, psoriasis, generalized dermatitis, pediculosis, urticaria ...etc), and any medication with potential pruritic properties.
- •Patients whose pruritus occurred only during dialysis
- •Patients received oral drugs with presumed antipruritic effect, including benzodiazepines, muscle relaxants, opioid analgesics, tricyclic antidepressants and antiepileptic drugs, or ultraviolet B phototherapy in the past one week prior to participate in this trial or during the trial.
- •Concomitant elevation of liver enzymes (GOT: male >37 U/L, female:>31 U/L, GPT: male >41 U/L, female:>31U/L), alkaline phosphatase (ALP>104U/L), bilirubin (T-bil>1.2 mg/dL), serum phosphorus (>7 mg/dl), serum parathyroid hormone (>300 pg/ml).
- •Patients who have the history of allergy to pregabalin, any acute illness, liver cirrhosis, hepatic failure, decompensated heart failure, inability to give informed consent, or poor compliance.
- •Patients with uncontrolled psychiatric disease, active malignancy, and untreated hypothyroidism.
- •Female patients who are pregnant, are nursing, or want to become pregnant.
研究组 & 干预措施
Pregabalin
pregabalin 75mg daily for 12 weeks
干预措施: pregabalin 75mg daily for 12 weeks (Drug)
fexofenadine
fexofenadine 60 mg daily for 12 weeks
干预措施: fexofenadine 60 mg daily for 12 weeks (Drug)
Placebo
placebo 75 mg for 12 weeks
干预措施: placebo (Drug)
结局指标
主要结局
The changes in pruritus symptoms assessed by VAS
时间窗: Week0, week1-12, Week 14
All participants will receive telephone interviewed by CRC every week and the severity, intensity, frequency and distribution of pruritus are evaluated by visual analogue scale (VAS)at the baseline of the study, every week throughout the treatment period and 2 weeks after administration of the final dose of study medication.
次要结局
- The changes in pruritus score (PS), Skindex-10", "Brief Itching Inventory" and Itch Medical Outcomes Study(PS: Week0, week1-12, Week 14; Skindex-10", "Brief Itching Inventory" and Itch Medical Outcomes Study (MOS): week0, 3,6, 9, 12, 14)