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Follow-up and Outcome of Operative Treatment With Decompressive Release Of The Peroneal Nerve (FOOT DROP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04695834
Recruitment Status : Not yet recruiting
First Posted : January 5, 2021
Last Update Posted : January 5, 2021
Sponsor:
Collaborator:
KCE
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Peroneal Nerve Entrapment Procedure: Neurolysis peroneal nerve Other: Maximal physiotherapy Not Applicable

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 and ankle range of motion), quality of life (EQ-5D 5L and SF-36) 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.

Since studies comparing surgery versus no surgery or delayed surgery are challenging, a feasibility pilot study will be conducted in 5 centers in Belgium and 1 center in the Netherlands. The go / no-go criterion to embark on a full scale study is the recruitment of at least 14 patients in these 6 centers after 6 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 182 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective Multi-center Randomized Parallel-group
Masking: Single (Outcomes Assessor)
Masking Description:

All participants will be asked to wear long trousers to cover a potential scar at the level of the knee.

All patients will be asked to apply a bandage at the site of the operation (or the site of entrapment if there was no operation) Participants are not allowed to discuss their treatment with the outcome assessor.

Primary Purpose: Treatment
Official Title: A Prospective, Multi-center, Randomized, Parallel-group Controlled Trial to Compare Conservative Versus Surgical Treatment of Foot Drop in Peroneal Nerve Entrapment.
Estimated Study Start Date : March 2021
Estimated Primary Completion Date : July 2025
Estimated Study Completion Date : July 2026


Arm Intervention/treatment
Active Comparator: Conservative treatment

Patients that are randomized to the conservative arm of the trial. These patients will not be operated until primary endpoint is reached.

If necessary, cross-over can occur after primary endpoint is reached.

Conservative treatment is considered standard of care.

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

Active Comparator: Surgical treatment

Patients randomized to the surgical arm will be operated within 1 week after randomization (if possible within 2 days).

Neurolysis is considered standard of care.

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 an adequate decompression should extend beyond the bifurcation in the deep and superficial peroneal nerve and should involve cutting the intermuscular septa




Primary Outcome Measures :
  1. 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 ]

    Based on a literature analysis and patient feedback on the trial design, gait analysis and recovery of a normal gait pattern are crucial in the recovery of foot drop. In 90% of interviewed patients, success of treatment was related to improvement in gait. The distance covered during the six-minute walk test (6MWT) is validated and clinically used in gait analysis.

    6MWT: patients are instructed to walk as far as possible within six minutes (strokes of 30 meters of more).

    The minimal age- and sex-specific normal 6MWD is defined as 82% of the applied reference equations for prediction of the 6MWD. The reference value that will be used is 6MWDpred(m) = 868.8 - (ageyears x 2.99) - (gender x 74.7). The value for gender is 0 in male subjects and 1 in female subjects.



Secondary Outcome Measures :
  1. Time to recovery [ Time Frame: 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization) ]

    KEY SECONDARY ENDPOINT Time to recovery is defined as: the time necessary to cover the minimal age- and sex-specific normal distance in meters during the 6-minute walking test (6MWT) AND the time necessary for foot drop recovery to an MRC-score ≥ 4 for ankle dorsiflexion.

    The MRC-score is a clinical assessment of muscle strength. MRC-ranges from 0 to 5 with zero indicating no movement at all and 5 indicating normal muscle strength.

    The minimal age- and sex-specific normal 6-minute walking distance (6MWD) is defined as 82% of the applied reference equations for prediction of the 6MWD. The reference value that will be used is 6MWDpred(m) = 868.8 - (ageyears x 2.99) - (gender x 74.7). The value for gender is 0 in male subjects and 1 in female subjects.


  2. 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)) ]

    Medical Research Council (MRC)-score as clinical assessment of muscle strength. MRC-score ranges from 0 to 5.

    0: no movement

    1. contraction of muscle, but no movement
    2. movement, but not against gravity
    3. movement against gravity, but not against resistance
    4. movement against resistance
    5. normal strength

  3. 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)) ]

    Recovery of ankle dorsiflexion strength is essential in patients with foot drop. The use of dynamometry allows to document ankle dorsiflexion strength in an objective manner.

    Patients are asked to lay in supine position, with the knees extended. The test pad of the dynamometer is placed on the dorsal head of the first metatarsal bone. The patient is instructed to perform ankle dorsiflexion with maximal muscle strength. The best of three attempts is registered. Ankle dorsiflexion is measured and reported in both ankles (in kilograms). The ankle dorsiflexion strength ratio, defined as the ratio of ankle dorsiflexion strength in the affected ankle over ankle dorsiflexion strength in the healthy ankle will be calculated and reported


  4. 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)) ]

    Medical Research Council (MRC)-score as clinical assessment of muscle strength. MRC-score ranges from 0 to 5.

    0: no movement

    1. contraction of muscle, but no movement
    2. movement, but not against gravity
    3. movement against gravity, but not against resistance
    4. movement against resistance
    5. normal strength

  5. Complications and neurologic deficits: Sensory changes [ Time Frame: 10 days (surgery), 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization)) ]

    In a large retrospective patient series on peroneal nerve decompression after weight loss, Broekx et al. (2018) examined the recovery of sensory deficits. Symptoms qualified as sensory included the presence of hypoesthesia and/or paresthesia. They used the following system to assess sensory symptoms:

    1. Complete recovery: the absence of any sensory symptoms
    2. Partial recovery: patients with a minimum of sensory symptoms
    3. No recovery: patients with no improvement

  6. 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) ]

    The distance covered during the six-minute walk test (6MWT) is validated and clinically used in gait analysis.

    6MWT: patients are instructed to walk as far as possible within six minutes (strokes of 30 meters of more).

    The minimal age- and sex-specific normal 6MWD is defined as 82% of the applied reference equations for prediction of the 6MWD. The reference value that will be used is 6MWDpred(m) = 868.8 - (ageyears x 2.99) - (gender x 74.7). The value for gender is 0 in male subjects and 1 in female subjects.


  7. Gait assessment: Stanmore questionnaire [ Time Frame: 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization) ]
    The Stanmore questionnaire has been used in the literature to assess functional outcome in patients with foot drop due to peroneal nerve injury. Seven sections (pain, need for orthosis, normal shoes, functional outcome, muscle power, degree of active dorsiflexion and foot posture) add up to a sum score of 100 points.

  8. Gait assessment: Functional ambulation categories [ Time Frame: 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization) ]

    Functional ambulation categories (FAC) is a useful scale to assess gait in patients with foot drop. It is a six point scale, that is used in stroke literature and can help determine how much assistance a patient requires.

    FAC 0 reflects a nonfunctional state and FAC 5 equals a normal gait pattern.


  9. 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) ]
    Walking speed is an important aspect of gait and is often used as an objective measure of functional mobility. The 10-meter walk test is a commonly used and validated tool to assess gait speed.

  10. Health economic assessment: Work Productivity and Activity Impairment Questionnaire (WPAI) [ Time Frame: 6 weeks and 6 months after randomization ]

    Health economic aspects of foot drop will be evaluated through the Work Productivity and Activity Impairment Questionnaire (WPAI). The WPAI is widely used and validated in multiple languages.

    The WPAI questionnaire consists of 6 questions with regard to professional activity during the past 7 days.


  11. Complications and neurologic deficits: Surgical complications [ Time Frame: 10 days, 6 weeks and 18 months after surgery ]
    A list of possible complications is made available to all participating centers. Unforeseen complications will be recorded as free-text.

  12. Electrodiagnostics: evolution of conduction block at the level of the fibular head [ Time Frame: 3 months and 9 months after randomization. ]
    All patients will have repeated electrodiagnostic examinations. The evolution of the conduction block at the level of the fibular head will be documented in the eCRF.

  13. Patient-reported outcome measurements regarding health-related quality of life: 5 Level Euro Quality of Life 5 Dimensions (EQ5D-5L) [ Time Frame: 10 days (surgery), 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization) ]
    The EQ-5D 5L is a generic measure of health-related quality of life developed by the EuroQol Group. It is a validated measurement of quality of life widely used in different pathologies. The questionnaire is made up of two parts. The first part is descriptive and uses five different dimensions to score quality of life. These five dimensions are mobility, self-care, activities of the daily life, pain/discomfort and anxiety/depression. There are five different answer possibilities within each dimension, i.e. "no problem", "slight problem", "moderate problem", "severe problem" and "unable to". This renders 3125 different answer possibilities. The second part uses a visual analogue scale (VAS) to score the current health status of the patient, ranging from zero to one hundred. Zero corresponds to death and one hundred corresponds to a (subjective) perfect health status.

  14. Health economic assessment: Return to work [ Time Frame: 6 weeks ]

    Health economic aspects will also be evaluated through the assessment of return to work. We expect subgroups of patients with foot drop to be unable to work. Once the foot drop has improved (or fully recovered), we expect patients to be able to return to work and to not experience any more related problems (after their initial recovery). In this trial population foot drop does in general not represent a chronic condition with periods of relapse. Either the foot drop recovers enough to be able to work again, or the foot drop does not sufficiently recover to resume previous professional activities.

    Taking this into account, return to work seems to represent a very important measure. Patients will be asked about return to work at the study visit six weeks after randomization. To avoid recall bias, patients will be asked in advance to record the date of return to work. During baseline assessments, subjects will be questioned if they are incapacitated to work due to the foot drop and the


  15. Gait assessment: The proportion of patients in both groups who reach minimal normal age- and sex-specific reference values for distance covered in meters during the six-minute walk test [ Time Frame: 9 months after randomization ]

    The distance covered during the six-minute walk test (6MWT) is validated and clinically used in gait analysis.

    6MWT: patients are instructed to walk as far as possible within six minutes (strokes of 30 meters of more).

    The minimal age- and sex-specific normal 6MWD is defined as 82% of the applied reference equations for prediction of the 6MWD. The reference value that will be used is 6MWDpred(m) = 868.8 - (ageyears x 2.99) - (gender x 74.7). The value for gender is 0 in male subjects and 1 in female subjects.


  16. Complications and neurologic deficits: Motor changes as assessed by the Medical Research Council Score (MRC-score) for ankle eversion [ Time Frame: 10 days (surgery), 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization) ]

    Medical Research Council (MRC)-score as clinical assessment of muscle strength. MRC-score ranges from 0 to 5.

    0: no movement

    1. contraction of muscle, but no movement
    2. movement, but not against gravity
    3. movement against gravity, but not against resistance
    4. movement against resistance
    5. normal strength

  17. Patient-reported outcome measurements regarding health-related quality of life: Short Form (36) Health Survey [ Time Frame: 10 days (surgery), 6 weeks, 3 months, 6 months, 9 months and 18 months (after randomization) ]
    The SF-36 health survey is a measure of health status and consists of eight scaled scores: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health. The SF-36 is a validated health survey and is available in different languages.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, …).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04695834


Contacts
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Contact: Christophe Oosterbos, M.D. +3216344290 christopheoosterbos@gmail.com
Contact: Tom Theys, M.D.; Ph.D. +3216344290 tom.theys@uzleuven.be

Locations
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Belgium
AZ Groeninge, department of neurosurgery
Kortrijk, West-Vlaanderen, Belgium, 8500
Contact: Jeroen Ceuppens, M.d.       jeroen.ceuppens@azgroeninge.be   
Principal Investigator: Jeroen Ceuppens, M.D.         
ULB Erasme, department of neurosurgery
Brussels, Belgium, 1000
Contact: Sophie Schuind, M.D.       sophie.schuind@ulb.erasme.ac.be   
Principal Investigator: Sophie Schuind, M.D.         
Ziekenhuis Oost-Limburg, department of neurosurgery
Genk, Belgium, 3600
Contact: Frank Weyns, M.D.    +3289326043    frank.weyns@zol.be   
Principal Investigator: Frank Weyns, M.D.         
University Hospitals Of Leuven, department of neurosurgery
Leuven, Belgium, 3000
Contact: Tom Theys, M.D., Ph.D.    +3216344290    tom.theys@uzleuven.be   
Principal Investigator: Tom Theys, M.D.; Ph.D.         
CHU de Liège, department of neurosurgery
Liège, Belgium, 4000
Contact: Annie Dubuisson, M.D., Ph.D.       a.dubuisson@chuliege.be   
Principal Investigator: Annie Dubuisson, M.D.; Ph.D.         
Netherlands
Leids Universitair Medisch Centrum, department of neurosurgery
Leiden, Netherlands, 2333
Contact: Justus Groen, M.D.       J.L.Groen@lumc.nl   
Principal Investigator: Justus Groen, M.D.         
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
KCE
Investigators
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Principal Investigator: Tom Theys, M.D.; Ph.D. Univeristy hospitals of Leuven
Publications:

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Responsible Party: Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT04695834    
Other Study ID Numbers: S62895
KCE19-1232 ( Other Grant/Funding Number: KCE Belgium )
First Posted: January 5, 2021    Key Record Dates
Last Update Posted: January 5, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Universitaire Ziekenhuizen Leuven:
Peroneal nerve
Neurolysis
Conservative treatment
Randomised controlled trial
Foot drop
Additional relevant MeSH terms:
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Nerve Compression Syndromes
Peroneal Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Mononeuropathies