Pilot RCT of Efficacy of Perineural Local Anesthetics and Steroids for Chronic Post-traumatic Ankle and Foot Pain (PREPLANS)

A Pilot Randomized Controlled Trial of Efficacy of Perineural Local Anesthetics and Steroids for Chronic Post-traumatic Neuropathic Pain in the Ankle and the Foot: The PREPLAN Study

Injections of local anesthetics (freezing) and steroids are often performed around injured nerves in individuals with nerve injury-related pain. The current standard of medical care is to inject a combination of local anesthetics and steroids around injured nerves, but there is no proof that this is better than injecting only local anesthetic, or even just sterile salt water. There is evidence to believe 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. The aim of this study is to compare pain relief and possible adverse effects from these three different treatments for foot and ankle nerve pain relief.

All 30 participants will be recruited over 9 months from the Altum Health clinic at Toronto Western Hospital. 10 participants will be randomly assigned to each treatment. Each patient will receive 3 injections over 3 weeks or so. Participants will have an in-clinic follow-up at 1 month after the last injection, and a phone follow-up 3 months after the last injection.

This is a small-scale study, and information obtained from this study will help in planning and conduct of a larger study with more participants. The larger study will help determine the best possible option for injection in patients with nerve-related injury pain.

Study Overview

• Status: Completed
• Conditions: CHRONIC POST-TRAUMATIC NEUROPATHIC PAIN IN ANKLE AND FOOT
• Intervention / Treatment: Drug: 0.9% saline; Drug: 0.25% bupivacaine hydrochloride injectable suspension USP; Drug: 4mg/cc methylprednisolone acetate injectable suspension USP

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T2S8
      • Toronto Western Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 and/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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 0.9% saline (salt water); 0.5mL 0.25% bupivacaine subcutaneous injection, 2-6cc 0.9% saline injection per nerve (20cc max)	Drug: 0.9% saline; Other Names: Salt Water
Active Comparator: local anesthetic (freezing); 0.5mL 0.25% bupivacaine subcutaneous injection, 2-6cc 0.25% bupivacaine per nerve (20cc max)	Drug: 0.25% bupivacaine hydrochloride injectable suspension USP; Other Names: Marcaine
Active Comparator: local anesthetic (freezing) and steroid; 0.5mL 0.25% bupivacaine subcutaneous injection, 2-6cc 0.25% bupivacaine and 4mg/cc methylprednisolone per nerve (20cc max)	Drug: 0.25% bupivacaine hydrochloride injectable suspension USP; Other Names: Marcaine; Drug: 4mg/cc methylprednisolone acetate injectable suspension USP; Other Names: Depo-Medrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enrollment and retention of participants (SEE DESCRIPTION)	Factors considered in assessment: Enrolling at least 75% of eligible patients, enrolling at least 9 patients monthly, retention till study end of at least 90% of participants	At end of study (1 year)

Secondary Outcome Measures

Outcome Measure	Time Frame
Central tendency (mean) and spread (standard deviation) of Numerical Rating Score (NRS) ratings of Foot and Ankle pain	At 1-month and 3-months post-intervention
Change in scores of Pain Catastrophizing Score (PCS)	Baseline and at 1-month post-intervention
Change in scores of Dolores Neuropathique (DN4)	Baseline and at 1-month post-intervention
Change in scores of Neuropathic Pain Symptom Inventory (NPSI)	Baseline and at 1-month post-intervention
Change in scores of anxiety component scores on the Hospital Anxiety and Depression Scale (HADS)	Baseline and at 1-month post-intervention
Change in scores of depression scores on the Patient Health Questionnaire-9 (PHQ-9)	Baseline and at 1-month post-intervention
Change in scores of Brief Pain Inventory interference with activities (BPI-I)	Baseline and at 1-month post-intervention
Change in scores of Short Form-12 (SF-12)	Baseline and at 1-month post-intervention
Change in scores of Lower Extremity Function Score (LEFS)	Baseline and at 1-month post-intervention
Evaluate the impact of study interventions on requirement for opioids (measured as average daily oral morphine equivalents in mg) and neuropathic medications (average daily doses of gabapentin and/or amitriptyline in mg)	At end of study (1 year)
Change in pre- and post-intervention levels of blood glucose and blood pressure	Baseline and at 1-month post-intervention
Measure incidence of infections at the injection site, skin discoloration or atrophy at the injection site, fractures, and evidence of myopathy	Baseline and at 1-month post-intervention

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Anuj Bhatia, MD, FRCPC, University Health Network, Toronto

Publications and helpful links

General Publications

• Bhatia A, Bril V, Brull RT, Perruccio A, Wijeysundera D, Alvi S, Lau J, Gandhi R, Mahomed N, Davis AM. Study protocol for a pilot, randomised, double-blinded, placebo controlled trial of perineural local anaesthetics and steroids for chronic post-traumatic neuropathic pain in the ankle and foot: the PREPLANS study. BMJ Open. 2016 Jun 22;6(6):e012293. doi: 10.1136/bmjopen-2016-012293. Erratum In: BMJ Open. 2016 Jul 04;6(7):e012293corr1.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: December 11, 2015
• First Submitted That Met QC Criteria: February 8, 2016
• First Posted (Estimate): February 11, 2016

Study Record Updates

• Last Update Posted (Actual): May 3, 2018
• Last Update Submitted That Met QC Criteria: April 30, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: methylprednisolone; neuropathic pain; ankle pain; foot pain
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Physiological Effects of Drugs; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Anesthetics, Local; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Bupivacaine
• Other Study ID Numbers: 15-9584-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO