Localized Neuropathic Pain: Topical Treatment Versus Systemic Treatment

Study Overview
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Brief Summary
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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)).

Detailed Description
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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).

Official Title
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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

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Drug: Lidocaine patch 5%
* Drug: Capsaicin 8% Patch
* Drug: Pregabalin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A multicentre, randomized, open-label comparative trial evaluating topical treatment options (lidocaine 5% or capsaicine 8% patch) versus oral systemic treatment (pregabaline as standard of care) in adult patients suffering from localized neuropathic pain (LNP) syndromes.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine patch 5%<br>Lidocaine 5% medicated plasters will be applied daily, during 12 consecutive hours. | Drug: Lidocaine patch 5%<br>* Application of Lidocaine 5% patch for 12 hours.<br>|
| Experimental: Capsaicin 8% patch<br>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<br>* Application of Capsaicin 8% patch for<br>|
| Active Comparator: Pregabaline<br>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<br>* Oral treatment with pregabalin (75mg capsules) will be used at optimized doses to best match clinical practice in Europe.<br>|

What is the study measuring?
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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 |