Pregabalin for the Treatment of Uremic Pruritus

Sponsor

National Taiwan University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT01852318

Collaborator

Cathay General Hospital (Other)

210

Enrollment

Location

Arms

Duration (Months)

16.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Uremic Pruritus	Drug: pregabalin 75mg daily for 12 weeks Drug: fexofenadine 60 mg daily for 12 weeks Drug: placebo	Phase 4

Detailed Description

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.

Methods:

This is a multicenter RCT. Haemodialysis patients with established UP were enrolled from multiple medical centers in Taiwan. All patients will be randomly allocated to receive one of three treatments -pregabalin 75mg daily, fexofenadine 60 mg daily, or placebo-for 12 weeks. The primary endpoint of the study is the change in the visual analogue score and pruritus score. The changes in QoL measures, including Skindex-10, Brief Itching Inventory and Itch Medical Outcomes Study, are also assessed before, during and after therapy. Safety is assessed at all visits throughout the study. A follow-up visit will be performed 2 weeks after administration of the final dose of study

Study Design

Study Type:

Interventional

Anticipated Enrollment :

210 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Double-blind, Randomized, Placebo and Active-controlled Study of Pregabalin for the Treatment of Uremic Pruritus

Study Start Date :

Apr 1, 2014

Anticipated Primary Completion Date :

May 1, 2015

Anticipated Study Completion Date :

May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pregabalin pregabalin 75mg daily for 12 weeks	Drug: pregabalin 75mg daily for 12 weeks oral pregabalin 75mg daily for 12 weeks
Active Comparator: fexofenadine fexofenadine 60 mg daily for 12 weeks	Drug: fexofenadine 60 mg daily for 12 weeks fexofenadine 60 mg daily for 12 weeks
Placebo Comparator: Placebo placebo 75 mg for 12 weeks	Drug: placebo

Arm

Intervention/Treatment

Experimental: Pregabalin

pregabalin 75mg daily for 12 weeks

Drug: pregabalin 75mg daily for 12 weeks

oral pregabalin 75mg daily for 12 weeks

Active Comparator: fexofenadine

fexofenadine 60 mg daily for 12 weeks

Drug: fexofenadine 60 mg daily for 12 weeks

fexofenadine 60 mg daily for 12 weeks

Placebo Comparator: Placebo

placebo 75 mg for 12 weeks

Drug: placebo

Outcome Measures

Primary Outcome Measures

The changes in pruritus symptoms assessed by VAS [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.

Secondary Outcome Measures

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]
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) and pruritus score (PS)29-30 at the baseline of the study, every week throughout the treatment period and 2 weeks after administration of the final dose of study medication. Because uremic pruritus has a great potential to impair the patients's quality of life (QoL), we adapt"Skindex-10", "Brief Itching Inventory" and Itch Medical Outcomes Study (MOS), proposed previously by Mathur et al.,12 to assess the effect of pregabalin treatment on the health-related quality of life in hemodialysis patients. These QoL measures are evaluated by clinicians at the baseline, every three weeks during treatment period and 2 weeks after administration of the final dose of study medication.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

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.