Mixed Peripheral Nerve Injury, Motor Peripheral Nerve Injury, Peripheral Nerve Discontinuity, Peripheral Nerve Injury, Upper Extremity Nerve Injury
Conditions
Keywords
Avance Nerve Graft, Sural Nerve Autograft, Processed Nerve Allograft, Peripheral Nerve Reconstruction, Mixed Nerve Repair, Motor Nerve Repair, MRCC, Nerve Gap, Nerve-RESTORE
Brief summary
This is a multicenter, 1:1 randomized, prospective, comparative study in participants requiring reconstruction of a mixed or motor nerve in the upper extremity. This study will consist of a screening visit, an operative visit, and 9 post-operative follow-up visits at Week 4, and Months 3, 6, 9, 12, 15, 18, 21, and 24.
Detailed description
This is a multicenter, 1:1 randomized, prospective, evaluator blinded, comparative study in participants requiring reconstruction of a mixed or motor nerve in the upper extremity. The study will assess recovery of motor and sensory function via MRCC score for nerve repairs with Avance Nerve Graft (Study Treatment) and sural nerve autograft (Comparator) through non-inferiority analyses. Participants will be considered enrolled to the study once all screening and eligibility criteria have been met and the participant has been centrally randomized to either Avance Nerve Graft or sural nerve autograft; Inclusion and exclusion criteria are defined at decision points for pre-operative screening eligibility and operative eligibility. This study will consist of a screening visit, an operative visit, and 9 post-operative follow-up visits at Week 4, and Months 3, 6, 9, 12, 15, 18, 21, and 24.
Interventions
BIOLOGICALAvance Nerve Graft
A commercially available, sterile, single-use peripheral nerve scaffold indicated for the treatment of functional deficits, manufactured from decellularized and sterilized extracellular matrix derived from human peripheral nerve tissue.
PROCEDURESural nerve autograft
A patient's own peripheral nerve tissue harvested in a secondary surgical procedure of the lower extremity where a functioning sural nerve is sacrificed for use in the reconstruction of a nerve defect.
Sponsors
Axogen Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Blinding of the surgeon, study participant and clinical research coordinator to the treatment group is not possible, and attempts will be made to maintain the blind for the upper extremity sensory and motor function outcomes assessor. Repair of a nerve discontinuity necessarily requires the surgeon to perform one of two procedures with distinct procedural characteristics that differ in operative steps, surgical locations, and graft appearance, making surgeon blinding infeasible. The study participant will also be unblinded due to the presence or absence of a donor-site harvest wound and a newly created functional deficit at the autograft donor site. The assessments for sensory and motor function will be conducted by a qualified assessor who has been blinded to the participant's treatment group. The lower extremity assessments for participants in the sural nerve autograft group will be conducted by a separate, qualified assessor who is not blinded to the participant's treatment group.
Intervention model description
Participants meeting the inclusion and exclusion criteria are centrally randomized in a 1:1 ratio intra-operatively, following stratification by longest gap length and nerve injured, and all nerve injuries qualifying for study enrollment shall be reconstructed with the same randomly assigned treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Study Participant Criteria 1. Be ≥ 18 years of age at the time of consent; 2. Willing and able to comply with all aspects of the treatment and evaluation schedule over a 24-month duration; 3. Provide documented Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent prior to initiation of any study procedures; Injury/Repair Criteria for Each Nerve 4. Primary or secondary nerve injury repair with sural nerve autograft or Avance Nerve Graft for fully transected reconstruction of the following upper extremity mixed and/or motor nerve(s): * Median nerve: proximal nerve stump within 20 cm from the center point of the thenar eminence and distal to the crease of the elbow; * Anterior interosseous nerve; * Median nerve recurrent motor branch; * Radial nerve: proximal nerve stump within 20 cm of the center of the forearm (midpoint between the tip of the olecranon and the styloid process) and distal to the mid-humerus; * Posterior interosseous nerve. 5. Zone of injury of eligible nerve(s) resectable to healthy nerve both distally and proximally and within the anatomical regions of Inclusion Criterion #4; 6. In study participants with multiple eligible nerve repairs, repair of all eligible nerves completed with the same study treatment, either Avance Nerve Graft or sural nerve autograft; 7. Measured nerve gap(s) following resection \> 25 mm; 8. Nerve(s) repaired ≤ 120 days post injury; 9. Undergo coaptation on both the proximal and distal portion of the nerve gap(s) per the USPI for Avance Nerve Graft and per standard of care for sural nerve autograft; and 10. Either treatment method, Avance Nerve Graft or sural nerve autograft, is a viable option for all eligible nerve repair(s) (i.e., volume of injured nerve\[s\] does not exceed availability of sural nerve autograft for reconstruction, study participants are not treated with a combination of treatment types).
Exclusion criteria
Study Participant Criteria 1. Currently enrolled in another clinical study that may interfere with treatment, assessment of recovery, or participation in this study; 2. Deformities or injuries of the limb, hand, or digits that affect both the primary and secondary assessments for eligible nerve repair(s); 3. History of neuropathy of any etiology, diabetic neuropathy or any other known neuropathy including compressive/traumatic neuropathies affecting the target limb; 4. History of progressive neurodegenerative or autoimmune disorder affecting peripheral nerve or motor function (e.g., amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease); 5. History of chronic ischemic condition of the upper extremity; 6. Expected use of medication during the study that is known to impact nerve regeneration or to cause peripheral neuropathy; 7. Undergoing or expected to undergo treatment with chemotherapy, radiation therapy, or other known treatment which affects the growth of neural and/or vascular systems; 8. Participant is unlikely to comply with all study requirements and standard medical care procedures for the duration of the study schedule; Injury/Repair Criteria for Each Nerve 9. Median nerve repairs where the ulnar nerve has been transected due to injury or repair; 10. Repair(s) of a sensory-only proximal nerve stump; 11. Incomplete nerve transections; 12. Multilevel nerve injury pattern requiring two or more isolated reconstructions along the nerve pathway (for example, reconstruction of median nerve in forearm and recurrent motor branch resulting in repair pattern of graft to native nerve to graft to distal target); 13. Inadequate soft tissue coverage or extensive soft tissue injury which will impair recovery assessment; 14. Nerve avulsion injuries and nerve traction injuries resulting in rupture of the nerve; 15. Replantation/amputation of the limb, hand, or digits involved in both the primary and secondary assessments for eligible nerve repair(s); 16. Nerve repairs utilizing either end-to-side or side-to-side coaptation techniques; 17. Nerve transfer, tendon transfer, or other concomitant treatment at the time of nerve repair that affects assessment of function of the innervated muscle organ; 18. Use of coaptation devices that include metallic components or activated polymers and coaptations completed with fibrin glue only; and 19. Injuries with vascular damage resulting in inadequate perfusion despite repair (i.e., both radial and ulnar arteries injured \[one injured artery is allowed\]).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recovery of motor function | Assessed at 24 months | Medical Research Council Classification (MRCC) of motor recovery score. This is an ordinal scale from M0-M5, with grade M0 meaning no contraction and M5 meaning full recovery in all muscles. |
| Recovery of sensory function | Assessed at 24 months | Medical Research Council Classification (MRCC) of sensory recovery score. This is an ordinal scale from S0-S4, with grade S0 meaning absence of sensibility in the autonomous area and S4 meaning complete recovery (2-point discrimination, 2-6 mm). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Meaningful recovery (MR) of motor and sensory function | Assessed at Week 4, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24 | Medical Research Council Classification (MRCC) of motor recovery score. Meaningful recovery is defined as ≥ M3 MRCC of motor recovery and ≥ S3 MRCC of sensory recovery. |
| Treatment response (TR) of motor and sensory function | Assessed at Week 4, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24 | Medical Research Council Classification (MRCC) of motor recovery score. Treatment response is defined as a 1-point increase in MRCC score from post-operative baseline. |
| Time to MR of motor and sensory function | Assessed at Week 4, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24 | Time from surgery to meaningful recovery of motor function in all repairs and of sensory function in mixed nerve repairs. |
| Time to TR of motor and sensory function | Assessed at Week 4, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24 | Time from surgery to treatment response of motor function in all repairs and of sensory function in mixed nerve repairs. |
| QuickDASH upper extremity disability score | Assessed at 24 months | The QuickDASH questionnaire (including Work and Sports/Performance Art modules if applicable) is a PROM questionnaire to measure physical functions and symptoms in participants with upper limb musculoskeletal disorders and will be used to assess the study participant's functional quality of life (QoL)as it pertains to the affected arm. This 11-item questionnaire addresses arm-specific symptoms and disability during the preceding week and is used to estimate the participant's view of disability. Each item is based on an ordinal scale from 1 to 5, where higher values are worse. QuickDASH scores range from 0 to 100, with a score of 0 indicating no disability and a score of 100 representing the most severe disability. |
| Lower Extremity Functional Scale (LEFS) score | Assessed at 24 months | The LEFS is a valid and reliable assessment for documenting function for individuals and groups with injury or disability to the lower extremity. It is based on the World Health Organization's model of disability and handicap and is applicable to a wide variety of participants with lower extremity orthopedic conditions, including participants with a range of disability levels, conditions, diseases, treatments, and ages. Applicable to sural nerve autograft group only. The LEFS consists of 20 questions, with each activity rated from 0 (extremely difficult or unable) to 4 (no difficulty). Scores range from 0 to 80, where higher scores indicate better lower limb function. |
Countries
United States
Contacts
CONTACTStacy Arnold
CONTACTHayley Nicolosi
PRINCIPAL_INVESTIGATORR. Glenn Gaston, MD
OrthoCarolina Research Institute, Inc.
Outcome results
None listed