Pregabalin for the Treatment of Uremic Pruritus

NCT ID: NCT01852318

Last Updated: 2014-04-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2015-05-31

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.

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

Conditions

Uremic Pruritus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pregabalin

pregabalin 75mg daily for 12 weeks

Group Type: EXPERIMENTAL

pregabalin 75mg daily for 12 weeks

Intervention Type: DRUG

oral pregabalin 75mg daily for 12 weeks

fexofenadine

fexofenadine 60 mg daily for 12 weeks

Group Type: ACTIVE_COMPARATOR

fexofenadine 60 mg daily for 12 weeks

Intervention Type: DRUG

fexofenadine 60 mg daily for 12 weeks

Placebo

placebo 75 mg for 12 weeks

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Interventions

pregabalin 75mg daily for 12 weeks

oral pregabalin 75mg daily for 12 weeks

Intervention Type: DRUG

fexofenadine 60 mg daily for 12 weeks

fexofenadine 60 mg daily for 12 weeks

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cathay General Hospital

OTHER

Sponsor Role: collaborator

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hsien-Yi Chiu, MD

Role: PRINCIPAL_INVESTIGATOR

2. Department of Dermatology, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan

Locations

National Taiwan University (NTUH); NTUH Hsin-Chu Branch; NTUH Yun-Lin Branch; Cathay General hospital

Taipei, Taiwan, Taiwan

Countries

Taiwan

Central Contacts

Hsien-Yi Chiu, MD

Role: CONTACT

extra.owl0430@yahoo.com.tw

0972654317

Tsen-Fang Tsai, MD

Role: CONTACT

tftsai@yahoo.com

886-2-23123456 ext. 2141

Facility Contacts

Hsien-Yi Chiu, MD

Role: primary

extra.owl0430@yahoo.com.tw

0972654317

References

Hercz D, Jiang SH, Webster AC. Interventions for itch in people with advanced chronic kidney disease. Cochrane Database Syst Rev. 2020 Dec 7;12(12):CD011393. doi: 10.1002/14651858.CD011393.pub2.

Reference Type: DERIVED

PMID: 33283264 (View on PubMed)

Other Identifiers

T-NTUH-8407

Identifier Type: OTHER

Identifier Source: secondary_id

201301065MINB

Identifier Type: -

Identifier Source: org_study_id