Safety and Efficacy of Lidocaine Versus Ketamine Infusion for Resistant Orofacial Pain

Safety and Efficacy of Lidocaine Versus Ketamine Infusion or Both Together as a Treatment Modality in Patient With Resistant Orofacial Pain; Double Blinded Randomized Study.

A prospective, randomized, double-blind clinical trial comparing the safety and efficacy of intravenous lidocaine, ketamine, and their combination as treatment options for patients suffering from treatment-resistant orofacial pain. The study measures pain reduction primarily using the Visual Analog Scale and evaluates safety and tolerability over a follow-up period of 6 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Orofacial Pain
• Intervention / Treatment: Drug: Lidocaine Intravenous Infusion; Drug: Ketamine intravenous infusion; Drug: Combined lidocaine and ketamine intravenous infusion

Detailed Description

This study aims to assess and compare the analgesic efficacy and safety profiles of intravenous lidocaine, ketamine, and a combined infusion of both in adult patients with orofacial pain that is resistant to conventional medical or interventional therapies. Using a randomized, double-blind design, 105 patients will be allocated equally into three parallel groups receiving either lidocaine infusion (5 mg/kg over 4 hours), ketamine infusion (0.3 mg/kg over 4 hours), or a combination infusion of lidocaine (2.5 mg/kg) and ketamine (0.15 mg/kg) over 3 consecutive weeks. Primary efficacy will be assessed by changes in pain intensity measured by the Visual Analog Scale (VAS) from baseline through follow-up visits at the 2nd and 3rd infusions, and 1, 3, and 6 months post-treatment. Secondary outcomes include cortisol level changes, depression assessment via PLAT-Q, and adverse events monitored during and after infusions. Strict inclusion and exclusion criteria will ensure patient safety and reliability of results. Data will be analyzed using one-way ANOVA and repeated measures ANOVA for continuous variables with significance set at p < 0.05.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Adults aged > 18 years

Resistant orofacial pain patients with failed medical or interventional treatment

Diagnosed with one or more of the following:

Trigeminal neuralgia

Temporomandibular joint (TMJ) dysfunction

Malignant otitis externa

Migraine

Atypical facial pain

Exclusion Criteria:

- Debilitating cardiac disease

Uncontrolled hypertension

Known allergies to lidocaine or ketamine

Severe renal or hepatic impairment

Pregnancy or breastfeeding

History of substance abuse

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lidocaine Infusion Group	Drug: Lidocaine Intravenous Infusion; Participants receive a slow intravenous infusion of lidocaine at a dose of 5 mg/kg (not exceeding 500 mg in total), diluted in 0.9% saline and administered over a 4-hour period, once weekly for three consecutive weeks. Continuous monitoring of cardiovascular and neurological status is provided during and after infusion to assess for efficacy and safety in cases of treatment-resistant orofacial pain.
Experimental: Ketamine Infusion Group	Drug: Ketamine intravenous infusion; Participants receive a slow intravenous infusion of ketamine at a dose of 0.3 mg/kg, diluted in 0.9% saline and delivered over 4 hours, once weekly for three consecutive weeks. The procedure includes monitoring for cardiovascular and CNS adverse effects. This intervention aims to evaluate the analgesic and safety profile of ketamine in patients with persistent orofacial pain unresponsive to standard therapies.
Experimental: Lidocaine-Ketamine Combination Group	Drug: Combined lidocaine and ketamine intravenous infusion; Participants receive a single intravenous infusion containing both lidocaine (2.5 mg/kg) and ketamine (0.15 mg/kg) diluted in 0.9% saline, administered over 4 hours, once weekly for three consecutive weeks. This intervention is designed to determine whether the combination of lidocaine and ketamine provides synergistic analgesic effects and improved tolerability compared to either drug alone in treating resistant orofacial pain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visual Analog Scale (VAS) Pain Score	Reduction in pain intensity as measured using the Visual Analog Scale (VAS), a 0-10 scale where 0 represents no pain and 10 represents the worst pain imaginable. The VAS will be assessed at baseline (before the first infusion) and at each follow-up visit (prior to 2nd infusion, prior to 3rd infusion, 1 month, 3 months, and 6 months after the intervention) to determine the effect of each treatment on resistant orofacial pain.	Baseline, prior to 2nd infusion, prior to 3rd infusion, 1 month, 3 months, and 6 months after intervention

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Orofacial Pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Facial Pain
• Other Study ID Numbers: Lidocaine versus Ketamine

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No