RECRUITING STUDIES

Metacarpal fractures are common and functionally displaced fractures may benefit from internal fixation with plates and screws. Drilling the bone and placing a screw through both cortices is the traditional method or orthopaedic fracture fixation but poses a small risk to the volar structures. Fracture complications including mal-union or non-union are rare and the study is designed to evaluate whether fixing with shorter unicortical screws is adequate for stability to achieve satisfactory bone union.

The study was developed in Birmingham with Katie Young, the first HaPPeN junior research fellow, Fieran Wu, an orthopaedic trainee in the West Midlands and Rajive Jose, a consultant in the Birmingham Hand Centre and Chief Investigator for the trial. 

Pilot funding was received through a grant from the RCDM and the trial is adopted to the NIHR portfolio. The trial is looking to recruit over 3 years and is multi-centre with 2 centres outside of Birmingham. 

Colonel Mark Foster is the Principle Investigator for the submit study at UHB. Recruitment is predicted to end Q4 2020 with final results available summer 2021.

The CoNNECT study is an investigator led study developed by the HaPPeN team and run in conjunction with the Surgical Reconstruction and Microbiology Research Centre in the Institute of Translational Medicine at UHB. The trial is supported by a commercial grant from POLYGANICS BV, Netherlands, a biomedical device company that has developed the Neurolac TM bioresorbable polymer nerve conduit. 

The surgical techniques are recorded and presented using the OrthOracle education platform and the technical guides are used to deliver training workshops in trial methodology for surgeons recruiting patients to the study.

The trial has three arms and will evaluate whether addition of a conduit around a microsurgical neurorraphy confers a functional advantage and whether a suture less repair technique reduces complications including repair-site neuroma in continuity formation. 240 nerves are to be recruited over three years at the Birmingham Hand Centre. 90 patients have enrolled in the study in Q1 2019 and the interim 6 month data analysis will be be presented at the IFSSH meeting in Berlin in June  2019. 

The EHands EPR system at the Birmingham Hand Centre provides valuable information on patient recruitment, epidemiology and injury patterns. The 18 month recruitment data has been published in the Journal of Musculoskeletal Surgery and Research in January 2019. 

RANGER: Registry of Avance Nerve Graft Evaluating Utilization and Outcomes for the Reconstruction of Peripheral Nerve Discontinuities

The RANGER Study is a multi-centre international registry study evaluating the utility, safety and efficacy of the AVANCE TM processed nerve allograft in the management of nerve gaps. The registry opened in the USA in 2018 and there are 21 centres actively recruiting to the study dataset. Dominic Power is the chief investigator for the UK and site Principle Investigator for the Birmingham Hand Centre and the West Midlands Brachial Plexus and Peripheral Nerve Injury Service at UHB. The HaPPeN team are the first centre outside North America to join the study and are contributing their experience of the AVANCE to the 1600 nerve reconstructions collected to date.

AxoGen Inc., Alachua, Florida, is a biomedical company specialising in the management of peripheral nerve disorders. The AVANCE TM processed nerve allograft is a nerve graft substitute derived from human nerve tissue that can be used to bridge nerve gaps. The structure provides endometrial tubes with removal of neurological-inhibitory proteins. The AVANCE TM can be used as a substitute for autologous nerve graft to eliminate the donor site morbidity associated with harvest of the patient's own nerves.

The HaPPeN team receive funding to assist in collection of utilisation and efficacy data for the use of AVANCE TM processed nerve allograft at UHB.

Suzanne Beale is the lead investigator for this rehabilitation study delivered through the HaPPeN team at UHB.

The aim of this study is to establish a standardised evidence-based protocol following median nerve repair, clinically evaluating measurements that may predict the need for early surgical intervention if the nerve is not progressing as predicted.  The four main clinical assessment parameters used will be the Progressing Tinel, the Differential Tinel's sign, the Tender Muscle Sign and Thermographic Imaging.

SCOPING is an observational study that commenced recruitment in Q1 2018 at UHB. The study population is complete transection injury of the median nerve at the wrist or in the distal third of the forearm.

The primary outcome measure used will be the Mackinnon Modified British Medical Research council (MRC) sensory scale. The secondary outcome measures used will be the static and moving 2PD, Semmes Weinstein Monofilaments Test (SWMT), Medical Research Council (MRC) Motor scale, Pain scale, Cold Intolerance Scale, Hyperaesthesia and patient reported outcomes DASH, EQ5D and PEM.  

Patients will be assessed at standardised intervals of 2 weeks, 6 weeks, 3 months, and additional research visits at 6 months, 9 months, 12 months and 18 months.  We will then standardise the assessments required at each interval of treatment. All patients will be assessed and treated by the lead therapist. 

Sample Size: This is a pilot sample size in an observational study. Working on 25-40 patients per year it is feasible to be able to recruit 12 patients to be assessed and reviewed over a period of 24 months allowing for over recruitment of 20%. The recruitment target is set at  0.5 patients per month.

Surgery: All patients will have undergone a repair of the median nerve within Zone VI (0-10 cms proximal to the volar wrist crease).

Inclusion Criteria: 

• Adult patients (>18 years) sustaining acute hand injuries with median nerve division that can be directly apposed for surgical repair with no gap. Repair up to 10 cms proximal to the volar wrist crease.

Exclusion criteria: 

• Patients with a history of local wound infection.
• History of prior injury to the median nerve.
• History of median nerve compression or cervical radiculopathy.
• History of conditions that may cause peripheral neuropathy.
• An inability to understand the examination instructions due to language barriers
• Patients not consenting to inclusion in the study.
• Pregnancy
• Prisoners
• 
  

Data Collection:

1.  Age, sex, occupation, hand dominance, co-morbidities

2.  Date of injury

3.  Date of surgery

4.  Baseline sensory function

5.  Consent for thermal imaging

6.  Surgical findings

7.  Operation performed – direct repair of the median nerve 

Primary Outcome Measure:

1.  Mackinnon Modified British MRC Sensory Scale. 

The Mackinnon Modified British MRC sensory scale was chosen has the primary outcome measure as it is a recognised tool used in the literature and is less time consuming to use than other outcome measures.

Secondary Outcome Measures: 

1.  Medical Research Council (MRC) motor scale

2.  Semmes-Weinstein Monofilament Test (SWMT)

3.  Static and moving 2PD

4.  Autonomic Grading scale- Likert scale

5.  Pain Intensity Grading scale – Likert scale

6.  Cold Intolerance Grading scale – Likert scale

7.  Hyperaesthesia Grading scale – Likert scale

8.  Disabilities of the Arm, Shoulder and Hand (DASH) 2

9.  Patient Evaluation Measure (PEM) questionnaire

10.  EQ5D

Grant funding:

This study has been funded by QEHB charities. 

References:

1. Wang Y, Sunitha M, Chung K (2013) “How to Measure Outcomes of Peripheral Nerve Surgery” Hand Clinics June 2013.
2. Hudak P, Amadio PC, Bombardier C, and the Upper Extremity Collaborative Group. Development of an Upper Extremity Outcome Measure: The DASH (Disabilities of the Arm, Shoulder, and Hand). American Journal of Industrial Medicine 1996; 29:602-608.

Caroline Miller leads the COMBINE study which has established an international patient and clinician core outcome dataset for reporting outcomes after adult traumatic brachial plexus injury. The study is in the final phase and dissemination through presentations and publications is underway.

The Match study is a cohort control arm within the RANGER study. The Birmingham Hand Centre and the West Midlands Brachial Plexus and Peripheral Nerve Injury Service jones the Match study in July 2018.

The study is evaluating utilisation and efficacy of autologous nerve grafts in gap management after peripheral nerve injury. 

Injury patterns, trauma severity, delay to reconstruction, method of reconstruction and distance to re-innervation are just some of the many variables influencing outcome from nerve injury. The variables are an impediment to recruiting to small cohort studies or multi-centre RCTs and as such the RANGER registry provides an opportunity for large scale data collection with sufficient powering to allow sub-group analyses.

The HaPPeN team are grateful to the sponsor AxoGen Inc. for allowing the UK to join this USA based study and pool experience in peripheral nerve reconstruction for the benefit of patients. 

The HaPPeN team receive funding support from AxoGen for delivery of anonymised utilisation and efficacy data, allowing the clinical team to collect standardised outcomes in a robust and more consistent way that enables comparison with published data in this field.