Localized Neuropathic Pain: Topical Treatment Versus Systemic Treatment (PELICAN)

Safety, Efficacy and Patient Acceptability of Topical Treatment Versus Systemic Treatment: a Randomized, Multicentre, Comparative Pragmatic Trial in Adult Patients Suffering From Diverse Localized Neuropathic Pain (LNP) Syndromes

Evaluation of topical treatment with lidocaine 5% patch (daily administration) or capsaicin 8% patch (periodic administration - upon reoccurrence of pain symptoms) in adult patients suffering from localized neuropathic pain (LNP) across a wide variety of etiologies, with a duration between 1 and 24 months (subacute to chronic neuropathic pain (NP)).

Study Overview

• Status: Terminated
• Conditions: Neuropathic Pain
• Intervention / Treatment: Drug: Lidocaine patch 5%; Drug: Capsaicin 8% Patch; Drug: Pregabalin

Detailed Description

A multicentre, randomized, open-label comparative trial evaluating topical treatment options versus oral systemic treatment in adult patients suffering from localized neuropathic pain (LNP) syndromes. A wide variety of peripheral neuropathic pain syndromes will be included such as post-herpetic neuralgia (PHN), post-surgical NP/post-traumatic NP/scar pain, post-amputation NP, post-radiation therapy NP, complex regional pain syndrome (CRPS) type 1. In contrast to most (or even all) commercial clinical studies we will not limit the inclusion to one or two distinct neuropathic pain syndromes such as post-herpetic neuralgia (inclusion based on etiology of the neuropathic syndrome). In this pragmatic trial we will however include all patients suffering from a clinical neuropathic syndrome with distinct clinical features such as hyperalgesia/allodynia, presence of spontaneous positive sensory phenomena and lasting for more than 3 months without making any exclusion based on etiology. Initial pain intensity indicates the presence of either moderate or severe pain in these adult patients (NRS 4/10).

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2018
    • AZ Monica (campus Antwerpen)
  • Brasschaat, Belgium, 2930
    • AZ Klina
  • Brugge, Belgium, 8000
    • AZ Sint Jan Brugge
  • Brussels, Belgium, 1020
    • UVC Brugmann
  • Charleroi, Belgium, 6000
    • Grand Hôpital de Charleroi
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg (ZOL
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent (UZG)
  • Jette, Belgium, 1090
    • UZ Brussel
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven (UZL)
  • Liège, Belgium, 4000
    • Hopital Universitaire Sart Tilman de Liège (ULg) (CHU)
  • Roeselare, Belgium, 8800
    • AZ Delta
  • Turnhout, Belgium, 2300
    • AZ Turnhout
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • University Hospital Antwerp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients eligible for inclusion in this study must fulfil all of the following criteria:

• Subjects should be capable of giving their informed consent with sufficient knowledge of the Dutch, French or German language;
• Males and females, 18 years and older;
• Be assessed as suffering from moderate to severe neuropathic pain across the screening process with pain intensity (numeric rating scale - NRS) ≥ 4/10,
• At the time of screening pain symptoms have to be present for at least one (1) month, with a maximum of 24 months;
• Sensory disturbances present in the skin area of maximal pain;
• At the time of screening pain is clearly related to the presence of a localized neuropathic pain syndrome.
• Male or female patients of child producing potential* must agree to use contraception or take measures to avoid pregnancy during the study and until after the final treatment;
• Women can only be included after negative pregnancy test;

Exclusion Criteria:

• Age < 18;
• Pregnant and breastfeeding women;
• Infection in the painful skin region;
• Poorly healed or non-healed wound or scar in the painful skin region as well as presence of cutaneous abnormalities (non-intact skin barrier) within the painful skin region related to dermatological conditions;
• Known and/or strong suspicion of allergy to the study medication, known skin disorder (resulting in disruption of the normal skin barrier);
• Previous treatment with any of the three medications included in the study protocol for the same painful area within the last 12 months at the time of screening;
• Risk of heart failure and/or renal failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lidocaine patch 5%; Lidocaine 5% medicated plasters will be applied daily, during 12 consecutive hours.	Drug: Lidocaine patch 5%; Application of Lidocaine 5% patch for 12 hours.
Experimental: Capsaicin 8% patch; Capsaicin 8% patches need to applied in a hospital setting during 1 hour. Re-application of these capsaicin patches will be performed upon re-occurrence of painful symptoms (mostly after 12 weeks - so not after a fixed time interval). Application of capsaicin patches will be carried out in a hospital setting (+/- 3 hours procedure).	Drug: Capsaicin 8% Patch; Application of Capsaicin 8% patch for
Active Comparator: Pregabaline; Oral treatment with pregabalin (75mg capsules) will be used at optimized doses to best match clinical practice in Europe. In European clinical practice, up-titration of the dose is often carried out over a longer time-period. This study thus includes up-titration schedule for pregabalin over a period of 4 weeks. If patients develop side-effects during the intake/uptitration of pregabalin this treatment can be stopped and switched to gabapentin (300mg capsules). Gabapentin will always be the back-up treatment for failed systematic treatment with pregabalin. Dose of gabapentin will be uptitrated to maximum 1200mg per day.	Drug: Pregabalin; Oral treatment with pregabalin (75mg capsules) will be used at optimized doses to best match clinical practice in Europe.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life questionnaire	To determine if topical treatment significantly improves health-related quality of life compared to systemic treatment in adult patients suffering from localized neuropathic pain across a wide variety of etiologies (LNP), with a duration between 1 and 24 months.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain relief	Reduction in pain intensity (PI-NRS), time to worsening of the pain (PI-NRS and NPSI) and use of rescue medication (MSQ III-R)	from week 0 up to 26 weeks
Health-related quality of life	AUC for EQ-5D-5L measurements, global perceived effect (GPE), effect on mood (HADS), quality of sleep (NRS and ISI).	from week 0 up to 26 weeks
Drug tolerance	Percentage of patients without systemic drug related side effects, percentage of patients who discontinue the study drug.	from week 0 up to 26 weeks
Functional status of the patient	Impact of pain on functioning (Interference - BPI), participation in activities (Utrecht Work Engagement Scale), Work Productivity and Activity Impairment (WPAI).	from week 0 up to 26 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Investigators: Principal Investigator: Guy Hans, MD, PhD, University Hospital, Antwerp

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Actual): April 19, 2021
• Study Completion (Actual): April 19, 2021

Study Registration Dates

• First Submitted: November 16, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (Actual): November 21, 2017

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Dermatologic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antipruritics; Lidocaine; Pregabalin; Capsaicin
• Other Study ID Numbers: R017007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No