Randomized Controlled Trial of Efficacy and Safety of Local Anesthetics and Steroids for Chronic Peripheral Post-traumatic Neuropathic Pain

NCT ID: NCT03009500

Last Updated: 2020-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2019-06-30

Brief Summary

The purpose of this study is to evaluate three different injectable solutions used to block ankle nerves to manage ankle pain. The current standard of medical care is to inject a combination of local anesthetics and steroids around injured nerves. There is evidence that injection of local anesthetic (without the steroid) can calm the injured nerve and provide pain relief from a few days up to a few months. Injection of sterile salt water also has the potential to provide pain relief by breaking scar tissue around the nerve thereby relieving compression. Injections of local anesthetic and steroids around injured nerves have been used for many years to provide relief of pain but the specific reason is not well known for this benefit.

There are three possibilities: 1) Steroids can reduce inflammation and calm the nerves, 2) local anesthetics can have similar actions but with shorter duration (few days), and 3) injection of any solution can break scarring around an injured/compressed nerve.

The study will compare pain relief and possible adverse effects from these three different solutions. This study will help provide definitive answers regarding pain relief and possible adverse effects of the three solutions. This, in turn, will determine the best possible option for injection in patients with nerve-related injury pain.

Detailed Description

This project is a randomized controlled trial with the aim of comparing efficacy of image (ultrasound)-guided administration of perineural combination of steroids and local anesthetic (current standard of care) against perineural local anesthetic (LA) or saline in providing sustained analgesic benefit in people with chronic neuropathic pain (NP) of the foot and ankle.

The study design will be multi-center, prospective, concealed, blinded, parallel group trial with three groups, block randomization (blocks of six participants) and allocation in a 2:2:2 ratio. Study participants and outcome evaluators will be blinded to treatment assignments.

Participants will be randomly assigned to one of the three groups to receive two US-guided injections (at an interval of one to two weeks) of one of the following around one or more of the five nerves innervating the foot and ankle:

The initial procedure will be repeated after one to two weeks unless clinical circumstances dictate otherwise (that is, the patient declined a second injection because of increase in pain or satisfaction with pain relief). The rationale for the repeat procedure is to allow possible benefit from a cumulative effect of the procedures and/or the injectates. Between the first injection and first follow-up visit, no patient will be allowed any additional therapeutic interventions. Nerves to be targeted by the injection will be decided by the treating physician based on area of the foot and ankle that displays features of neuropathic pain. Each injection of study medications will be preceded by subcutaneous injections of 1 mLs of LA (2% lidocaine) at each of the injection sites. This will reduce discomfort of the study participants from the injections. The subcutaneous LA will also cause numbness of the skin and this will ensure blinding of participants to their group allocation. Two ultrasound-guided procedures will be performed at weekly intervals over two weeks. The US-guided technique for performing these procedures has been described in previous studies from our center.22 Conservative measures (oral analgesics, physiotherapy) will continue during the study. Fasting blood glucose will be measured at baseline and at one month following the interventions. Systolic and diastolic blood pressure (with participant sitting for at least 5 minutes prior to the measurement) values will be recoded as a mean of three consecutive readings at baseline and at one month following the interventions. Cross-sectional area (CSA) of tibial nerve at 3 cm proximal to cephalad edge of medial malleolus will also be measured prior to the first procedure and prior to the second procedure in participants with pain in distribution of the tibial nerve. Change in CSA (if any) will be correlated with analgesic response to perineural injections because decrease in CSA may indicate reduction in edema of the nerve.

Conditions

Neuralgia; Peripheral Neuropathic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: DOUBLE

Study Groups

Local Anesthetic

Injection of 2-6 cc of LA (0.25% bupivacaine) per nerve to a maximum of 20 cc

Group Type: ACTIVE_COMPARATOR

Bupivacaine

Intervention Type: DRUG

Lidocaine

Intervention Type: DRUG

Each injection of study medications will be preceded by subcutaneous injections of 1 mLs of 2% lidocaine at each injection site to reduce discomfort of the study participants from the injections

Local Anesthetic with steroids

Injection of 2-6 cc of LA (0.25% bupivacaine) per nerve containing steroids (methylprednisolone (Depo-Medrol) 4 mg per cc) to a maximum of 20 cc

Group Type: ACTIVE_COMPARATOR

Bupivacaine

Intervention Type: DRUG

Depo-Medrol Injectable Product

Intervention Type: DRUG

Lidocaine

Intervention Type: DRUG

Each injection of study medications will be preceded by subcutaneous injections of 1 mLs of 2% lidocaine at each injection site to reduce discomfort of the study participants from the injections

Saline

Injection of 2-6 cc of saline (0.9% sodium chloride) per nerve to a maximum of 20 cc

Group Type: PLACEBO_COMPARATOR

Saline (Sodium Chloride) solution

Intervention Type: OTHER

Lidocaine

Intervention Type: DRUG

Each injection of study medications will be preceded by subcutaneous injections of 1 mLs of 2% lidocaine at each injection site to reduce discomfort of the study participants from the injections

Interventions

Bupivacaine

Intervention Type: DRUG

Depo-Medrol Injectable Product

Intervention Type: DRUG

Saline (Sodium Chloride) solution

Intervention Type: OTHER

Lidocaine

Each injection of study medications will be preceded by subcutaneous injections of 1 mLs of 2% lidocaine at each injection site to reduce discomfort of the study participants from the injections

Intervention Type: DRUG

Other Intervention Names

Marcaine; Methylprednisone

Eligibility Criteria

Inclusion Criteria

1. Pain in foot in neuro-anatomically congruent location following trauma (including surgery) for more than three months

2. Physician-reported DN4 scoring confirming neuropathic pain (score >3/10)

3. Average intensity of pain more than 3/10 on numerical rating score

4. Failed trial of appropriate doses of first line medications for neuropathic pain (anticonvulsants and/or antidepressants) for six weeks

Exclusion Criteria

1. Age < 18 or Age > 80 years

2. Perineural or intra-articular steroid injections in the last 6 months

3. Allergy to local anesthetics or steroids

4. Ongoing litigation issues related to the patient's pain

5. Pregnancy

6. Coagulopathy or systemic infection

7. Peripheral neuropathy or myopathy, central neuropathic pain (e.g. post-stroke pain)

8. Infection in the ankle or foot

9. An unstable medical or psychiatric condition

10. Significant catastrophizing as indicated by pain catastrophizing scale (PCS) score equal to or more than 30/52.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Anuj Bhatia

Director, Anesthesia Chronic Pain Clinical Services

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anuj Bhatia, MD FRCPC

Role: PRINCIPAL_INVESTIGATOR

UHN

Locations

Toronto Western Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

16-5927

Identifier Type: -

Identifier Source: org_study_id