Pregabalin for the Treatment of Uremic Pruritus

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by National Taiwan University Hospital
Sponsor:
Collaborator:
Cathay General Hospital
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01852318
First received: May 8, 2013
Last updated: April 13, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Uremic Pruritus
Drug: pregabalin 75mg daily for 12 weeks
Drug: fexofenadine 60 mg daily for 12 weeks
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • The changes in pruritus symptoms assessed by VAS [ Time Frame: Week0, week1-12, Week 14 ] [ Designated as safety issue: No ]
    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 [ Time Frame: PS: Week0, week1-12, Week 14; Skindex-10", "Brief Itching Inventory" and Itch Medical Outcomes Study (MOS): week0, 3,6, 9, 12, 14 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 210
Study Start Date: April 2014
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.

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

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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:

  1. 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.
  2. Patients whose pruritus occurred only during dialysis
  3. 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.
  4. 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).
  5. 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.
  6. Patients with uncontrolled psychiatric disease, active malignancy, and untreated hypothyroidism.
  7. Female patients who are pregnant, are nursing, or want to become pregnant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01852318

Contacts
Contact: Hsien-Yi Chiu, MD 0972654317 extra.owl0430@yahoo.com.tw
Contact: Tsen-Fang Tsai, MD 886-2-23123456 ext 2141 tftsai@yahoo.com

Locations
Taiwan
National Taiwan University (NTUH); NTUH Hsin-Chu Branch; NTUH Yun-Lin Branch; Cathay General hospital Not yet recruiting
Taipei, Taiwan, 100; 300; 640; 280
Contact: Hsien-Yi Chiu, MD    0972654317    extra.owl0430@yahoo.com.tw   
Principal Investigator: Hsien-Yi Chiu, MD         
Sponsors and Collaborators
National Taiwan University Hospital
Cathay General Hospital
Investigators
Principal Investigator: Hsien-Yi Chiu, MD 2. Department of Dermatology, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01852318     History of Changes
Other Study ID Numbers: 201301065MINB, T-NTUH-8407
Study First Received: May 8, 2013
Last Updated: April 13, 2014
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
uremic pruritus
pregabalin
gabapentin
fexofenadine

Additional relevant MeSH terms:
Pruritus
Skin Diseases
Skin Manifestations
Signs and Symptoms
Fexofenadine
Terfenadine
Gamma-Aminobutyric Acid
Pregabalin
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Histamine H1 Antagonists, Non-Sedating
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anticonvulsants
GABA Agents

ClinicalTrials.gov processed this record on July 10, 2014