Follow-up and Outcome of Operative Treatment With Decompressive Release Of The Peroneal Nerve

Official title

A Prospective, Multi-center, Randomized, Parallel-group Controlled Trial to Compare Conservative Versus Surgical Treatment of Foot Drop in Peroneal Nerve Entrapment.

Overview

The FOOT DROP trial is a prospective, multi-center, randomized controlled trial to assess if decompressive surgery for peroneal nerve entrapment is superior to maximal conservative treatment. Patients with persisting foot drop due to peroneal nerve entrapment will be randomized to either surgery or conservative treatment if foot drop persists 10 +/- 4 weeks after onset of symptoms. Patients will be evaluated through several questionnaires, evolution of muscle strength and several types of gait assessments. Primary endpoint is the difference in distance covered during the six minute walking test between baseline and 9 months after randomization.

Detailed description

The Foot Drop Trial is the first prospective, randomised controlled trial to investigate the treatment of foot drop in peroneal nerve entrapment. Currently, the literature consists mostly of biased retrospective case series with the exception of some small (biased) prospective case series. No comparative trials have been conducted. The goal of the trial is to assess whether foot drop due to peroneal nerve entrapment recovers better 9 months after decompressive surgery compared to maximal conservative treatment.

Patients with persisting foot drop (MRC score ankle dorsiflexion ≤ 3) after 10 +/- 4 weeks after onset of symptoms will be randomised to either decompressive surgery within 1 week after randomisation or maximal conservative treatment focussing on physiotherapy and gait rehabilitation. Blinded outcome assessors will evaluate participants at study visits 10 days (surgical group), 6 weeks, 3 months, 6 months, 9 months (primary outcome) and 18 months (extended follow-up) after randomization.

Outcome assessors will conduct several assessments to evaluate gait improvement (6-minute walk test, 10-meter walk test, Stanmore questionnaire, functional ambulation categories, ability to walk barefoot, need for foot-ankle orthosis), muscle strength (MRC score for ankle dorsiflexion, ankle eversion, hallux extension) , quality of life (EQ-5D 5L) and cost-effectiveness of both treatment strategies (work productivity and activity impairment questionnaire (WPAI), return to work, percentage of invalidity). Electrodiagnostic follow-up will be registered at 3 months and 9 months after randomization.

The primary endpoint of the foot drop trial is the difference in distance covered in meters during the six-minute walk test (6MWD) between baseline and 9 months after randomization. Time to recovery, defined as the time necessary to cover the minimal age- and sex-specific normal 6MWD AND the time necessary for foot drop recovery to an MRC-score ≥ 4 for ankle dorsiflexion is the key secondary endpoint. No cross-over to surgery is allowed before primary endpoint is reached.

The study first succesfully piloted in 6 centers in Belgium and the Netherlands and is currently starting on a large scale in 20 centers.

Interventions

• Procedure Neurolysis peroneal nerve
  The surgical approach for entrapment at the fibular head is usually through a curvilinear incision just distal to the fibular head. The subcutaneous tissue is bluntly dissected, and the common peroneal nerve is identified proximal to the peroneus longus muscle. The peroneal nerve is then released from the surrounding fibrous tissue and fascia. The nerve is decompressed distally as it dives under the peroneus longus muscle. The decompression at this site is essential. Certain authors state that a
• Other Maximal physiotherapy
  Mobilization of ankle and foot, stretching of the calf muscles (prevention of contractures) Tonification of the dorsiflexion- and eversion muscles of the ankle Proprioceptive training Gait rehabilitation Home exercise schedule

Primary outcome measures

• The difference in distance covered in meters during the six-minute walk test (6MWD) between baseline and 9 months after randomization. [Time frame: 9 months]

Secondary outcome measures (12)

• Time to recovery [Time frame: 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization)]
• Ankle dorsiflexion strength as measured by the Medical Research Council score (MRC-score). [Time frame: 10 days (surgery), 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization))]
• Ankle dorsiflexion strength as measured by isometric dynamometry. [Time frame: 10 days (surgery), 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization))]
• Complications and neurologic deficits: Motor changes as assessed by the Medical Research Council Score (MRC-score) for hallux extension [Time frame: 10 days (surgery), 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization))]
• Complications and neurologic deficits: Sensory changes [Time frame: 10 days (surgery), 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization))]
• Gait assessment: Difference in distance covered in meters during the six-minute walk test [Time frame: 6 weeks, 3 months, 6 months and 18 months (after randomization)]
• Gait assessment: Stanmore questionnaire [Time frame: 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization)]
• Gait assessment: Functional ambulation categories [Time frame: 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization)]
• Gait assessment: Gait speed as measured by the 10-meter walk test [Time frame: 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization)]
• Health economic assessment: Work Productivity and Activity Impairment Questionnaire (WPAI) [Time frame: 6 weeks and 6 months after randomization]
• Complications and neurologic deficits: Surgical complications [Time frame: 10 days, 6 weeks and 18 months after surgery]
• Electrodiagnostics: evolution of conduction block at the level of the fibular head [Time frame: 3 months and 9 months after randomization.]

Eligibility criteria

Inclusion criteria

• Written informed consent to participate in the study must be obtained from the subject or proxy / legal representative prior to initiation of any study-mandated procedure
• EDX-documented peroneal nerve entrapment with persisting (10 ± 4 weeks) foot drop (MRC-score ≤ 3)
• Imaging (ultrasound/MRI) performed to exclude a compressive mass
• Age ≥ 18 years

Exclusion criteria

• Subjects with posttraumatic or iatrogenic peroneal nerve injury
• Subjects with peroneal neuropathy due to a compressive mass (e.g. cyst, tumour)
• Peroneal nerve entrapment at other sites than the fibular head
• Patients with mental or physical problems that incapacitate them to participate in a physiotherapy program
• Psychiatric illness
• Pregnancy
• Planned (e)migration within 1 year after randomization to another country
• Subjects with previous foot drop
• Permanently bedridden subjects
• Subjects with neurological or musculoskeletal history which could impact foot drop assessment and/or gait analysis (e.g. polyneuropathy, hereditary neuropathy with pressure palsies, critical illness polyneuropathy, previous stroke, ankle surgery, …).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Belgium · 17 centers

• AZ Sint-Maarten — Mechelen
• AZ Turnhout — Turnhout
• Sint Augustinus — Wilrijk
• Jessa Ziekenhuis — Hasselt
• AZ Vesalius — Tongeren
• AZ Alma — Eeklo
• AZ Sint-Lucas — Ghent
• AZ Sint-Jan — Bruges
• … and 9 more centers

Netherlands · 1 center

• Leids Universitair Medisch Centrum, department of neurosurgery — Leiden

Publications

• Poage C, Roth C, Scott B. Peroneal Nerve Palsy: Evaluation and Management. J Am Acad Orthop Surg. 2016 Jan;24(1):1-10. doi: 10.5435/JAAOS-D-14-00420. PMID 26700629
• Broekx S, Weyns F. External neurolysis as a treatment for foot drop secondary to weight loss: a retrospective analysis of 200 cases. Acta Neurochir (Wien). 2018 Sep;160(9):1847-1856. doi: 10.1007/s00701-018-3614-9. Epub 2018 Jul 1. PMID 29961126
• Cruz-Martinez A, Arpa J, Palau F. Peroneal neuropathy after weight loss. J Peripher Nerv Syst. 2000 Jun;5(2):101-5. doi: 10.1046/j.1529-8027.2000.00007.x. PMID 10905469
• Khedr EM, Fawi G, Allah Abbas MA, El-Fetoh NA, Zaki AF, Gamea A. Prevalence of Common Types of Compression Neuropathies in Qena Governorate/Egypt: A Population-Based Survey. Neuroepidemiology. 2016;46(4):253-60. doi: 10.1159/000444641. Epub 2016 Mar 15. PMID 26974980
• Kandil MR, Darwish ES, Khedr EM, Sabry MM, Abdulah MA. A community-based epidemiological study of peripheral neuropathies in Assiut, Egypt. Neurol Res. 2012 Dec;34(10):960-6. doi: 10.1179/1743132812Y.0000000099. PMID 23146298
• Poppler LH, Bansal A, Groves A, Sacks G, Davidge K, Mackinnon SE. Abstract 65: Subclinical Peroneal Nerve Entrapment May be an Under-recognized Cause of Falls in Hospitalized Patients. Plast Reconstr Surg. 2014 Mar;133(3 Suppl):76. doi: 10.1097/01.prs.0000445098.29964.cf. No abstract available. PMID 25942176
• Aprile I, Caliandro P, La Torre G, Tonali P, Foschini M, Mondelli M, Bertolini C, Piazzini DB, Padua L. Multicenter study of peroneal mononeuropathy: clinical, neurophysiologic, and quality of life assessment. J Peripher Nerv Syst. 2005 Sep;10(3):259-68. doi: 10.1111/j.1085-9489.2005.10304.x. PMID 16221285
• Aprile I, Padua L, Padua R, D'Amico P, Meloni A, Caliandro P, Pauri F, Tonali P. Peroneal mononeuropathy: predisposing factors, and clinical and neurophysiological relationships. Neurol Sci. 2000 Dec;21(6):367-71. doi: 10.1007/s100720070052. PMID 11441574

Identifiers

NCT: NCT04695834 · S62895 · KCE19-1232

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗