Performance Study of an Artificial Nerve Guide (Reaxon® Nerve Guide) to Treat Digital Nerve Lesions

Study Overview
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Brief Summary
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The purpose of this clinical investigation is to confirm the medium- and long-term safety and performance of the chitosan-based nerve guide (Reaxon® Nerve Guide) in comparison to an autologous nerve graft to bridge nerve defects in the finger.

Detailed Description
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The clinical investigation NG-001 is a multicenter, parallel, controlled, randomized, blind evaluation of the repair of digital nerve lesions. Medovent will perform this clinical investigation as a post-market clinical follow-up (PMCF) study in accordance with the MEDDEV 2.12/2 rev2 guidelines to confirm the medium- and long-term safety and performance of its chitosan-based nerve guide (Reaxon® Nerve Guide). The results of this investigation will be used by Medovent to update the clinical evaluation throughout the life-cycle of Reaxon® Nerve Guide and to ensure its long term safety and performance in the market. Additionally, Medovent will include the application of Reaxon® Nerve Guide in digital nerves to confirm the safety of applying Reaxon® Nerve Guide over joints. The study will be performed in specialized German centers. A total number of 76 subjects with traumatic digital nerve injuries in whom surgical repair may not allow end-to-end direct suture of the nerve ends, and in whom the nerve tissue gap would indicate the use of an autograft of equal or less than 26 mm, are eligible for inclusion. The primary objective of the clinical investigation is to demonstrate that the static 2-point discrimination (2-PD) 12 months after surgery will be not inferior in the Reaxon® Nerve Guide test group compared to the control group receiving an autologous nerve graft. The secondary objective is to document the long-term effects (up to 18 months after surgery) in nerve repair. The non-inferiority test is to demonstrate that it can be excluded that the treatment difference is larger than 20% in favor for the control group.

Official Title
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A Controlled, Randomized, Comparison, Blind Evaluation of Repair of Digital Nerve Lesions in Man Using an Implanted Reaxon® Nerve Guide

Conditions
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Peripheral Nerve Injuries

Intervention / Treatment
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* Device: Implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males and females between 18 and 65 years of age able to give his/her consent a complete traumatic nerve injury of the common or proper digital nerve in the hand a nerve defect of less or equal than 26 mm after release and approximation of the nerve ends and measured when the wrist is in neutral position an injury that could conventionally be treated with implantation of a short nerve graft nerve treatment initiated until 3 months after nerve injury signed informed consent Exclusion Criteria: known allergy to chitosan and/or polyvinylpyrrolidone (PVP) known impairment / previous diseases of the neural axis or previous lesions of the affected hand (of the digital nerve), which led to permanent sensory or motor restrictions of the hand/finger complete amputation injury known pregnant or breast-feeding females disorders known leading to impaired wound healing (e.g. diabetes mellitus) skin diseases in the wound area impaired blood coagulation or bleeding disorders (e.g. because of regular intake of cumarin such as Marcumar) pathologic blood flow disorders (e.g. Morbus Raynaud) participated in another clinical investigation using an investigational new drug or device within 30 days prior to enrolment into this investigation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reaxon® Nerve Guide<br>Implantation of Reaxon® Nerve Guide: If the subject is randomized to the Reaxon® Nerve Guide group, the surgeon will implant a Reaxon® Nerve Guide of ≤ 30 mm to bridge a nerve defect of ≤ 26 mm according to the method described in the instructions for use. | Device: Implantation<br>* A peripheral nerve defect up to 26 mm in the finger will be repaired by implantation of either a Reaxon® Nerve Guide or an autologous nerve graft (depending on the randomization group) on day 0.<br>|
| Active Comparator: Autologous Nerve Graft<br>Implantation of an autologous nerve graft: If the subject is randomized to the conventional treatment, the surgeon will repair the nerve by interposing an autologous nerve graft of ≤ 26 mm between the nerve ends. | Device: Implantation<br>* A peripheral nerve defect up to 26 mm in the finger will be repaired by implantation of either a Reaxon® Nerve Guide or an autologous nerve graft (depending on the randomization group) on day 0.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Static 2-point discrimination (2-PD) | The perception of either one or two points of touch is assessed using a small tool with prongs at fixed spacing's from 2 to 15 mm. One or two points will be applied randomly in a longitudinal direction on the distal phalanx of all fingers. Grades/scores: 0 = > 15 mm (poor) = 11-15 mm (fair) = 6-10 mm (good) = < 6 mm (excellent) Scores of 2 or 3 will be evaluated as (meaningful) response. At a score of 0 it will further be determined if the subject has protective sensibility or is anesthetic. A disposable cannula can be used. Single point is noticeable = protective sensibility No point is noticeable = anesthetic | Primary outcome analysis will be performed from the clinical evaluations at 12 months post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Static 2-point discrimination (2-PD) | see description above | Baseline visit (latest 7 days post-surgery) + Follow-up examinations 3, 6, 12 and 18 months post-surgery | 
| Moving 2-PD | A moving stimulus of either one or two points is assessed using a small tool with prongs at fixed spacing's from 2 to 15 mm. One or two points will be moved randomly in a longitudinal direction from proximal to distal of all fingers. Grades/scores: see Static 2-PD | Baseline visit (latest 7 days post-surgery) + Follow-up examinations 3, 6, 12 and 18 months post-surgery | 
| Semmes-Weinstein Monofilament | The 5 kit monofilaments will be used. A monofilament is pressed against the skin at specific locations (see protocol) starting with the thinnest filament (i.e. 2.83) and then, depending on the response, thicker filaments are applied until the subject feels the pressure. Grades/scores: 0 = not testable = filament 6.65, perception of deep pressure = filament 4.56, no protective sensation = filament 4.31, diminished protective sensation = filament 3.61, diminished perception of light touch = filament 2.83, normal perception of light touch | Follow-up examinations 3, 6, 12 and 18 months post-surgery | 
| Subject's estimation of cold intolerance and hyperesthesia | The examiner will stroke the dysfuntional area and question the subject about cold intolerance and hypersensitivity. Grades/scores: 0 = Hinders function = Disturbing = Moderate = None/minor | Follow-up examinations 3, 6, 12 and 18 months post-surgery | 
| Hoffmann-Tinel-Test | The test is performed by lightly tapping over the nerve to elicit a sensation of tingling in the distribution of the nerve. The distance of the sensation from the distal end of the implant will be determined. | Follow-up examinations 3, 6, 12 and 18 months post-surgery | 
| post-operative complications | There will be evaluations of common post-operative complications associated with peripheral nerve repair surgery, i.e. painful neuroma formation, assessed by pain on percussion, allodynia, and dysaesthesia (pain and/or numbness). | Baseline visit (latest 7 days post-surgery) + Follow-up examinations 3, 6, 12 and 18 months post-surgery |