Arthroscopic vs. Open Bone Grafting for Scaphoid Delayed/Nonunion

Study Overview
=================
Brief Summary
-----------------
Single site, prospective, observer-blinded randomized controlled trial. Eighty-eight patients aged 18-68 years with scaphoid delayed/non-union, will be randomized, 1:1, to either open iliac crest cancellous graft reconstruction or arthroscopic assisted distal radius cancellous chips graft reconstruction. All Danish citizens, referred to the orthopedic department, Copenhagen University Hospital in Gentofte with scaphoid delayed/nonunion will be offered participation in the trial. Exclusion criteria are: Associated fracture in the hand/upper extremity, previous failed surgical treatment for scaphoid delayed/nonunion, stage 2 SNAC or above, avascular necrosis of the proximal pole and gross deformity. Patients are stratified for smoking habits, proximal pole involvement, and displacement of >/<2mm. The primary outcome is time to union, measured with repeated CT scans at 2-week intervals from 6 to 16 weeks postoperatively. Secondary outcomes are Quick disabilities of the Arm, Shoulder and Hand (Q-DASH), Visual Analogue scale (VAS), donor site morbidity, union rate, restoration of scaphoid deformity, range of motion, key-pinch, grip strength, EQ5D-5L, patient satisfaction, complications, and revision surgery. Patients are examined before the operation and 1.5, 3, 6, 12 and 24 month after the operation. Online follow-up 5 and 10 years after surgery are performed.

Detailed Description
-----------------
A scaphoid fracture is the most common injury to the carpal bones. The incidence is 107-151/100.000 per year and fractures are predominantly sustained by males in their twenties. Scaphoid non-union is defined as a lack of healing 6 months after injury and develops in 5-25% of cases after non-operative treatment. Delayed union is defined as incomplete healing 2-6 months after injury. However, some potential for a union probably exists, especially in nondisplaced fractures, otherwise this condition is associated with a transition into a persistent non-union. The risk of non-union increases with delayed diagnosis and treatment, displaced fractures, proximal pole fractures, smoking, poor vascularity, and advancing age. The scaphoid is primarily covered with cartilage and has a retrograde blood supply. The dorsal branch of the radial artery accounts for 80% and a separate volar branch for 20 % of the extramedullary blood supply. The proximal pole is only supplied by the intramedullary flow. Compromised blood supply can explain the potential of non-union and avascular necrosis of the proximal pole. The healing process can be complicated by volar angulation of the fracture leading to humpback deformity. This will disrupt carpal kinematics, and result in lunate instability and dorsal intercalated segment instability (DISI). Untreated scaphoid non-union can lead to degenerative changes, called scaphoid non-union advanced collapse (SNAC), and irreversible impairment such as pain and altered hand function. X-ray is commonly applied to evaluate the scaphoid, although CT scans are reportedly superior in terms of displacement, angulation and union[9]. Different measurements to describe the angulation and deformity of the scaphoid are suggested. The Height length ratio (HLR) and dorsal cortical angle (DCA) are found to be the most reliable measurements. Surgical treatment of scaphoid delayed/non-union is technically demanding and often results in a long period with a supportive bandage until union is established. Current treatment strategies for delayed union and non-union include vascularized or non-vascularized bone graft with internal fixation. Kirchner wires or screws have been the gold standard for fixation. Arthroscopic reconstruction with C chips and internal fixation is predominantly applied in delayed union and stable non-union. The advantages of arthroscopy include thorough wrist assessment, evaluation of concomitant ligamentous injury and minimal trauma to the ligament structures, joint capsule, and the tenuous blood supply. The objective of this study protocol is to describe the methodology for a RCT comparing time to union and functional outcome scores of arthroscopic assisted C chips reconstruction or open C graft reconstruction for scaphoid delayed/non-union Hypothesis: Arthroscopic assisted C chips graft reconstruction of scaphoid delayed/non-union is superior to open C graft reconstruction regarding faster time to union, by at least mean 3 weeks difference. Study design: This is a single-center, 1:1 observer-blinded randomized controlled, superiority trial. The main objective is to compare open C graft with arthroscopic assisted C chips graft reconstruction for scaphoid fractures with delayed/non-union. Subjects: A total of 88 patients with scaphoid delayed/non-union are randomized to either: Group A - Arthroscopic assisted C chips graft reconstruction (intervention group), n=44 Group O - Open C graft reconstruction (control group), n=44 Inclusion criteria: Patients aged 18-68 years. A scaphoid fracture without healing 2-6 months since fracture (delayed union) for cases with either displacement >1mm or comminution and failed non-operative treatment. Scaphoid fracture without healing >6 months since fracture (non-union) regardless of displacement, comminution and if previous non-operative treatment has been tried. ASA 1-3. Exclusion criteria: Open fractures Associated trans-scaphoid perilunate dislocation. Associated fracture in the hand/upper extremity. Previous failed surgical treatment for scaphoid delayed/non-union. Stage 2 SNAC or above. Avascular necrosis of the proximal pole as evaluated with MRI and absence of punctate bleeding intraoperatively. Patients with gross humpback deformity of HLR >0.75 and/or DCA <70⁰. Patients unable to understand instructions in Danish, complete the rehabilitation protocol, or answering the questionnaires because of physical or cognitive impairment, as evaluated by the surgeon at the first visit. Enrolment: All Danish citizens aged 18-68 years with scaphoid delayed/non-union referred to the hand surgery unit, Herlev and Gentofte University Hospital, will be offered participation in the study. Other hand unit departments in the Capital Region of Denmark will forward their referrals to our department for inclusion. The physician will review the medical records and assess whether the patients fulfil the inclusion/exclusion criteria. Patients will undergo a clinical examination and CT scan of the wrist to describe angulation (HLR and DCA), displacement, localization of non-union, presence of cysts, and degenerative changes. All patients with involvement of the proximal pole will undergo gadolinium-enhanced MRI to clarify vascularity, but the final assessment of avascular necrosis of the proximal pole will be performed perioperatively. If punctate bleeding after tourniquet being off for at least 5 minutes of expectation cannot be visible, the patient will then be excluded from the study and will be simultaneously operated with a vascular bone graft or a salvage procedure Randomization: Based on the sample size calculation, a total number of 88 patients will be allocated into two groups of equal size Group A - Arthroscopic assisted C-chips graft reconstruction (intervention group), N=44. Group O - Open C-only graft reconstruction (control group), N=44. The randomization is done in the outpatient clinic and the patients will be informed about the operative treatment. The randomization application, Research Electronic Data Capture (REDCap), will allocate patients in a 1:1 ratio, stratified for proximal pole fracture (yes /no), dislocation (>/< 2mm), and smoking (yes/ no). A statistician will generate a randomization sequence for RED-Cap. In this observer-blinded RCT, union is assessed by a blinded musculoskeletal radiologist. QDASH is a patient-reported survey, without the involvement of surgeons or research staff. Other secondary outcomes will be measured by an independent observer. The study will not be blinded to the operating theatre staff, surgeons, physiotherapists, or patients. Clinical outcomes and patient-reported outcomes will be measured after 1.5, 3, 6, 12, and 24 months. Online questionnaires will be sent after 5 and 10 years. Primary outcome is time to union, assessed with repeated CT-scans in two weeks interval from 6-16 weeks after operative treatment. Union will be proclaimed and recorded when >50% bone bridging occurs on CT. Secondary outcomes are: Q-DASH (patient reported outcome, questionnaire), range of Motion, grip strength and Key pinch (functional outcome). Finally, pain and donor site morbidity evaluated with VAS, Complications, EQ5D-5L (cost-utility measure) and patient satisfaction are recorded. The study will follow the Helsinki Declaration. All patients will receive oral and written information before the assignment of consent. Patients can withdraw their consent at any time. The Danish National Committee on Health Research Ethics has approved this study protocol (Journal-nr.: H-21075664). All patients in the study are covered by the insurance policies of ordinary treatment regarding complaints and compensation following the rules in the Act on Complaints and Compensation in the Health Services in Denmark. The background radiation in Denmark is 3 mSv pr. Year. The radiation dosage due to repeated CT scans of 0.03mSv, is a maximum 0.21mSv corresponding to approximately 21 days of background radiation. Patients with prolonged period to union or failed union are at risk of the increased radiation dosage compared to case/surgeon-specific conditions as standard treatment. The current standard treatment at our department includes follow up until the union is established. In this study, we will have additional follow-up examinations at 6 months and at 1 and 2 years. It has the risk of keeping the patients in the role of being ill. However, the patients can have a feeling of extra good care with the possibility to address uncertainty or problems more easily. Patients are at risk of being treated inferior with an intervention which is deemed inferior with the study analysis, but nothing a priori suggests which intervention is the better one. The trial will provide high-quality evidence regarding time to union, short- and long-term functional outcomes of open and arthroscopic assisted graft reconstruction for scaphoid delayed/non-union. The results from the study can contribute to establish a treatment algorithm for scaphoid delayed/non-union together with results from other studies. Neither the primary investigator, participation investigators, and sponsors have personal economic interests in the results of the study.

Official Title
-----------------
Arthroscopic Versus Open Cancellous Bone Grafting for Scaphoid Delayed/Non-union in Adults: Study Protocol for a Randomized Clinical Trial

Conditions
-----------------
Scaphoid Fracture, Scaphoid Nonunion

Intervention / Treatment
-----------------
* Procedure: Graft reconstruction and internal fixation with compression screw


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged 18-68 years. A scaphoid fracture without healing 2-6 months since fracture (delayed union) for cases with either displacement >1mm or comminution and failed non-operative treatment. Scaphoid fracture without healing >6 months since fracture (non-union) regardless of displacement, comminution and if previous non-operative treatment has been tried. ASA 1-3. Exclusion Criteria: Open fractures Associated trans-scaphoid perilunate dislocation. Associated fracture in the hand/upper extremity. Previous failed surgical treatment for scaphoid delayed/non-union. Stage 2 SNAC or above. Avascular necrosis of the proximal pole as evaluated with MRI and absence of punctate bleeding intraoperatively. Patients with gross humpback deformity of HLR >0.75 and/or DCA <70⁰. Patients unable to understand instructions in Danish, complete the rehabilitation protocol, or answering the questionnaires because of physical or cognitive impairment, as evaluated by the surgeon at the first visit.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 68 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 observer-blinded randomized controlled, superiority trial. The main objective is to compare open C graft with arthroscopic assisted C chips graft reconstruction for scaphoid fractures with delayed/non-union. Based on the sample size calculation, a total of 88 patients with scaphoid delayed/non-union are randomized to either: Group A - Arthroscopic assisted C chips graft reconstruction (intervention group), n=44 Group O - Open C graft reconstruction (control group), n=44 The randomization is done in the outpatient clinic and the patients will be informed about the operative treatment. The randomization application, Research Electronic Data Capture (REDCap), will allocate patients in a 1:1 ratio, stratified for proximal pole fracture (yes /no), dislocation (>/< 2mm), and smoking (yes/ no). A statistician will generate a randomization sequence for REDCap.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arthroscopic assisted Cancellous chips graft reconstruction<br>The arthroscopic technique is potentially less invasive with minimal donor site morbidity and potentially faster time to union because of minimal trauma to the ligament structures, joint capsule, and the tenuous blood supply. It may also have advantageous osteogenic properties compared to a structural graft. Currently, studies have reported similar union rates, patient reported outcomes score, and functional score compared to open graft technique. Results in patients with gross deformity are debated with some studies favoring conventional open structural graft and other found no difference in outcome between the techniques. | Procedure: Graft reconstruction and internal fixation with compression screw<br>* Patients suffering from scaphoid nonunion are treated surgically by debridement, graft reconstruction and internal fixation with compression screw<br>|
| Active Comparator: Open cancellous graft reconstruction<br>Convention open technique with debridement of the nonunion side, insertion of cancellous graft from the iliac crest and osteosynthesis with compression screw is currently commonly applied in scaphoid nonunion. | Procedure: Graft reconstruction and internal fixation with compression screw<br>* Patients suffering from scaphoid nonunion are treated surgically by debridement, graft reconstruction and internal fixation with compression screw<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Union | Assessed with CT-scans. Union is proclaimed if at least 50% bone bridging is recorded together with absence of pain in the clinical examination | 6-16 weeks postoperative in 2 weeks intervals. If unions is not achieved a CT will be made 26 weeks postoperatively. If union is not achieved at that point, the patient will be presented for another treatment modality | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Quick Disability of the Arm, Shoulder, and Hand (Q-DASH) | Q Dash is a patient-reported survey. It is a subset of 11 items from the 30-item DASH questions that assess difficulties with specific tasks: 5 concerning symptoms, 4 on social function, and 1 on work function, sleep, and confidence. The score ranges from 0-100 and the higher score reflects disabilities. The MCID has been defined as 10.8 (range, 5-15) for comparable patients. | Preoperatively, 1.5 md, 3md, 6md, 12md, 24md, 60md, and 120 months postoperative | 
| Union rate | Assessed with CT-scans | 6-16 weeks postoperative. If unions is not achieved a CT will be made 26 weeks postoperatively | 
| Correction of deformity | The Height length ratio (HLR) and dorsal cortical angle (DCA) are found to be the most reliable measurements to describe angulation. The height-length ratio is calculated by dividing the scaphoid height by length. | Before surgery compared to CT-scan with >50% bone bridging. | 
| Pain (VAS) | Pain at rest and activity is recorded on a visual analogue scale (VAS), ranging from 0-10, with 10 reflecting the worst and 0 representing no pain in the wrist. | Preoperatively, 1.5, 3, 6, 12, 24, 60, and 120 months postoperative | 
| Donor site morbidity | located to the iliac crest (Group O) and distal radius (Group A) are evaluated with VAS ranging from 0-10, with 10 reflecting the worst and 0 representing no pain in the wrist | Preoperatively, 1.5, 3, 6, 12, 24, 60, and 120 months postoperative | 
| Grip strength | is measured in kilograms with a Jamar dynamometer with the elbow will be in 90° flexion and attached to the chest compared to the unaffected. | Preoperatively, 1.5, 3, 6, 12, and 24 months postoperative | 
| Key pinch | is measured in kilograms using a pinch gauge with the elbow in in 90° flexion and attached to the chest, compared to the unaffected wrist. | Preoperatively, 1.5, 3, 6, 12, 24, 60, and 120 months postoperative | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Scaphoid, Scaphoid nonunion, Cancellous, Graft, Arthroscopic, Timo to union