Clinical trial NCT04570293: 5% Lidocaine-medicated Plaster for the Treatment of Trigeminal Neuralgia
Official title: The PATCH Trial: Effectiveness and Safety of 5% Lidocaine-medicated Plaster for the Treatment of Trigeminal Neuralgia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Trigeminal Neuralgia
Keywords: 5% Lidocaine-medicated Plaster
Trigeminal Neuralgia
Enriched Enrollment Randomized Withdrawal
Triggers
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2020-09-30
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Trigeminal neuralgia (TN) is characterized by sudden, severe, usually unilateral, transient, stinging, recurrent electrocute-like shock in one or more divisions of the trigeminal nerve, lasting from a few seconds to less than 2 minutes.Simple daily-life activities, such as washing the face, brushing the teeth, eating, and talking, or the slight touch of trigger points may trigger the attack of pain of TN, resulting in a decline in the patient's quality of life (QoL). Trigger zones predominantly locate in the perioral and nasal region. Paroxysmal pain is associated with triggers in virtually all patients with TN. TN may be caused by abnormality of the trigger zone and the blockade of Na+ channel of trigger zone may be a novel and effective treatment methods for TN. Currently, most patients with TN may not achieve adequate pain relief with a single therapeutic agent. Multiple analgesics targeting different mechanisms of the pain pathway are often used.5% lidocaine medicated plaster (LMP) is a white hydrogel plaster containing adhesive material. LMP was approved for post-herpetic neuralgia (PHN) treatment by the United States Food and Drug Administration (FDA) in 1999. Tamburin et al reported that 2 patients with primary TN who stopped oral drugs because of side effects or refused surgical procedures. Both patients were instructed to wear LMP over the affected area and LMP resulted in reduction of pain intensity and the number of pain paroxysms without side effects. However, due to limitations of these open-label design studies, the observed reductions in pain intensity may have been due to treatment effect, placebo effect, changes in underlying disease state, or a combination of these factors. Therefore, randomized controlled trials will be need to be performed to draw about the efficacy of the LMP in TN.

The PATCH trial is a prospective, double-blinded, vehicle-controlled, parallel-group, multicenter, enriched enrolment with randomized withdrawal (EERW) trial aimed at estimating the efficacy and safety of LMP in patients with TN. After providing informed consent and completing a baseline evaluation, patients will participate in an initial open-label treatment period of LMP (active patches). This openly titrated process is close to clinical practice and can provide data on the proportion of responders and non-responders, the optimal dose of the analgesic drug, and the proportion of withdrawal due to adverse effects. A responder at the end of the open-label treatment phase will be included in the subsequently double-blind treatment phase.


Eligibility criteria: Inclusion Criteria:

* Occurrence of episodes of intense facial paroxysmal pain in the distribution(s) of one or more divisions of the trigeminal nerve, triggered by innocuous stimuli;
* Average daily pain intensity ≥ 4 by a brief pain inventory-short form (BPI-SF) Item 5 score (0-10 rating scale of average pain) in the preceding 24-hour period;
* Concomitant analgesic regimens that include 14 days of stable doses with systemic analgesics rather than topical agents for relief of PHN will be permitted
* Normal neurologic examination;
* Normal neuroimaging analysis.

Exclusion Criteria:

* Atypical pain location (eg, no specific trigger points) or trigger zones in the mouth;
* Proposed surgical intervention due to preference of the patient;
* Any condition known to interfere with the correct execution of the sensory tests (eg, peripheral or central neurological dysfunction or cognitive impairments);
* Presence of any other acute or chronic pain disorder with the need of systemic analgesic medication for more than 10 days in the last 3 months;
* Inability to discontinue the use of another lidocaine-containing products or a class I anti-arrhythmic drug during the study period;
* History of hypersensitivity to an amide-type local anesthetic agent, or other contents of the lidocaine or vehicle patch;
* History of surgical intervention or neurological ablation to treatment TN;
* Participation in another clinical trial within 30 days of the study;
* Any patient who was judged to be unreliable or unable to understand the protocol procedures;
* Any abnormality of the skin or of vascular origin at application site;
* Pregnancy or breastfeeding;.

Primary outcomes:
measure: the number of treatment failures on LMP vs. number of treatment failures on vehicle patches throughout the double-blind treatment phase
timeFrame: Through study completion, an average of 7 weeks.
Secondary outcomes:
measure: Time to loss of therapeutic response (LTR)
timeFrame: During the double-blind phase after randomization, an average of 7weeks.
measure: Proportion of responders and non-responders
timeFrame: Through the open-label period, an average of 3 weeks.
measure: the proportion of the patients who report pain relief of 50% or greater
timeFrame: At 3 weeks, 7 weeks
measure: The pain intensity
timeFrame: Through study completion, an average of 7 weeks.
measure: The number of paroxysms
timeFrame: Through study completion, an average of 7 weeks.
measure: The severity of paroxysms
timeFrame: Through study completion, an average of 7 weeks.
measure: Quality of life (QoL)
timeFrame: Through study completion, an average of 7 weeks.
measure: Pittsburgh Sleep Quality Index (PSQI) at baseline, at end of open-label phase, and end of double-blind phase or premature discontinuation
timeFrame: At baseline, 3 weeks, 7weeks
measure: Short form 36 health survey questionnaire (SF-36) at baseline, end of open-label phase, and end of double-blind phase or premature discontinuation
timeFrame: At baseline, 3 weeks, 7weeks
measure: The cost of treatment
timeFrame: Through study completion, an average of 7 weeks.
measure: Patient Global Impression of Change (PGIC) at end of open-label phase, and end of double-blind phase or premature discontinuation
timeFrame: At 3 weeks, 7 weeks
measure: Study blindness
timeFrame: Through study completion, an average of 7 weeks.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing China-Janpan Friendship Hospital
city: Beijing
country: China
facility: Sanbo Brain Hospital, Capital Medical University
city: Jilin
country: China
facility: Jilin province people's hospital
city: Shanxi
country: China
facility: Linfen People's Hospital
Study officials:
affiliation: Beijing Tiantan Hospital
name: Fang Luo
role: PRINCIPAL_INVESTIGATOR
References:
citation: Di Stefano G, Maarbjerg S, Nurmikko T, Truini A, Cruccu G. Triggering trigeminal neuralgia. Cephalalgia. 2018 May;38(6):1049-1056. doi: 10.1177/0333102417721677. Epub 2017 Jul 14.
citation: Liu M, Zhong J. Mechanism underlying cranial nerve rhizopathy. Med Hypotheses. 2020 Sep;142:109801. doi: 10.1016/j.mehy.2020.109801. Epub 2020 May 6.
citation: Cheville AL, Sloan JA, Northfelt DW, Jillella AP, Wong GY, Bearden Iii JD, Liu H, Schaefer PL, Marchello BT, Christensen BJ, Loprinzi CL. Use of a lidocaine patch in the management of postsurgical neuropathic pain in patients with cancer: a phase III double-blind crossover study (N01CB). Support Care Cancer. 2009 Apr;17(4):451-60. doi: 10.1007/s00520-008-0542-x. Epub 2009 Jan 13.
citation: Gammaitoni AR, Alvarez NA, Galer BS. Safety and tolerability of the lidocaine patch 5%, a targeted peripheral analgesic: a review of the literature. J Clin Pharmacol. 2003 Feb;43(2):111-7. doi: 10.1177/0091270002239817.
citation: Tamburin S, Schweiger V, Magrinelli F, Brugnoli MP, Zanette G, Polati E. Effect of 5% lidocaine medicated plaster on pain intensity and paroxysms in classical trigeminal neuralgia. Ann Pharmacother. 2014 Nov;48(11):1521-4. doi: 10.1177/1060028014544166. Epub 2014 Jul 28.
citation: Zhao C, Shrestha N, Liu H, Shen Y, Meng L, Fan B, Luo F. The PATCH trial: efficacy and safety of 5% lidocaine-medicated plaster for the treatment of patients with trigeminal neuralgia: a study protocol for a multicentric, double-blind, enriched enrolment randomised withdrawal, vehicle-controlled study. BMJ Open. 2021 Aug 2;11(8):e045493. doi: 10.1136/bmjopen-2020-045493.