Duroplasty for Injured Cervical Spinal Cord With Uncontrolled Swelling

Study Overview
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Brief Summary
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QUESTION. Does duroplasty improve outcome after spinal cord injury? WHAT DO WE STUDY? We will investigate whether performing a surgical procedure called duroplasty improves outcomes after spinal cord injury. WHY SPINAL CORD INJURY? Spinal cord injury is a devastating condition that causes permanent disability such as paralysis, numbness and loss of bladder and bowel control. Currently, there are no treatments shown to improve outcome after spinal cord injury. WHAT IS DUROPLASTY? Duroplasty is an operation that involves opening the tough membrane around the cord, called the dura, and stitching a patch of artificial dura to expand the space around the swollen cord. WHY IS DUROPLASTY BEING STUDIED? Based on our preliminary evidence, we think that the dura causes cord pressure after injury. We have shown in a small study of patients that performing this operation safely and effectively reduces pressure on the injured cord. WHO IS ELIGIBLE? Adult patients with severe spinal cord injuries in the neck who will have surgery within 72 hours. WHAT TREATMENT? Those who agree to take part will be allocated by chance (like tossing a coin) to standard treatment or standard treatment plus duroplasty. Some patients will also be asked to take part in a smaller study that involves placing probes at the injury site. WHERE? We will recruit patients from U.K. Major Trauma Centres. Most assessments will be done in U.K. Spinal Injury Centres. Later on, we may recruit from overseas. HOW LONG? We aim to recruit 222 - 260 patients over 4 years. Patients will be followed up for a year. WHAT DO WE ASSESS? Patients will be assessed (using questionnaires and by examination) how well they can use their hands, walk, control their bladder and bowel and their quality of life. Some of these assessments will be repeated at 3, 6 and 12 months after surgery. WHAT IS THE OPTIONAL MECHANISTIC STUDY? DISCUS includes an optional study for at least 50 patients who will take part in the randomised controlled trial. The aim of the mechanistic study is to determine how duroplasty improves outcome, i.e. whether duroplasty reduces cord compression, improves blood flow to the injured cord perfusion, improves cord metabolism and reduces cord inflammation. WHAT IS THE OPTIONAL INFORMATION STUDY? For the first two years, a study called QuinteT Recruitment Intervention (QRI) is designed to optimise patient recruitment and informed consent in the trauma setting.

Detailed Description
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RESEARCH QUESTION: After severe traumatic spinal cord injury (TSCI), does the addition of dural decompression to bony decompression (includes laminectomy) improve muscle strength in the limbs at 6 months, compared with bony decompression alone? BACKGROUND: TSCI is a devastating condition that affects about 1,000 people in the UK annually. Most remain disabled, tetraplegic or wheelchair bound and are dependent on carers with significant cost to patients, carers and the NHS. Surgery aims to reduce spinal deformity, stabilise the spine and achieve bony decompression of the cord. To date, no treatments have been shown to improve outcome. AIMS / OBJECTIVES: The primary aim is to determine if, in patients with acute, severe TSCI, the addition of dural decompression to bony decompression improves muscle strength. We hypothesise that, after TSCI, the cord swells and is compressed against the dura. Secondary objectives are to assess patient impact i.e. functional outcomes, health related quality of life (HRQoL), complication rates and mortality. Mechanistic sub-studies aim to determine if the addition of duroplasty improves cord perfusion, reduces cord ischaemia and cord inflammation. METHODS: This is a prospective, phase III, multicentre randomised controlled trial (RCT). We aim to recruit 222 adults with acute, severe cervical TSCI (American spinal injuries association Impairment Scale (AIS) grade A, B or C) who will be randomised 1:1 to undergo bony decompression alone versus bony decompression with duroplasty. Patients and assessors will be blinded to study arm. The primary outcome is change in AIS motor score (AMS) at 6 months compared with admission (Delta-AMS); secondary outcomes will assess function (grasp, walking, urinary + anal sphincters), HRQoL, complications, need for further surgery and mortality, assessed at baseline, 3 months, 6 months and 12 months from randomisation. A subgroup of 50 patients (25 per arm) will also have observational monitoring from the injury site using a pressure probe (intraspinal pressure ISP, spinal cord perfusion pressure SCPP) and microdialysis (MD) catheter (cord metabolism: tissue glucose, lactate, pyruvate, lactate-to-pyruvate ratio (LPR), glutamate, glycerol); cord inflammation: tissue chemokines/cytokines. Patients will be recruited from the 26 UK major trauma centres (MTCs). TIMELINES FOR DELIVERY: The study duration is 72 months and includes 6 months set-up, 48 months recruitment, 12 months to complete follow-up and 6 months for data analysis and final reporting of results. There will be a formal stop/go review at month 15 (after 9 months of recruitment) to ensure a minimum of 4 sites have been opened and 8 patients randomised. If these targets are met, the trial will recruit for a further 36 months. Data from the pilot will be included in the final analysis. ANTICIPATED IMPACT AND DISSEMINATION: It is anticipated that the addition of duroplasty to standard of care will improve muscle strength in patients; this has obvious benefits for patients and their carers as well as substantial gains for the NHS and society including economic implications. If this RCT shows that the addition of duroplasty to standard treatment is beneficial, it is anticipated that duroplasty will become standard NHS care in all 26 UK MTCs. Participants will be informed of study findings via the Surgical Intervention Trials Unit (SITU) website and the Spinal Injuries Association (SIA).

Official Title
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Duroplasty for Injured Cervical Spinal Cord With Uncontrolled Swelling

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Procedure: Duroplasty
* Procedure: Spinal surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥16 years Severe cervical (C2 - T1) traumatic spinal cord injury (AIS grade A-C) Deemed to require and be suitable for surgery that includes laminectomy by local surgeon Surgery within 72 hours of traumatic spinal cord injury Able to provide informed consent or consultee declaration or proxy consent. Exclusion Criteria: Dural tear due to traumatic spinal cord injury Life-limiting or rehabilitation-restricting co-morbidities Thoracic or lumbar traumatic spinal cord injury Other central nervous system disease

Ages Eligible for Study
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Minimum Age: 16 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
Interventional Model Description: Phase III clinical trial: randomised, controlled, double blind, multi-centre, superiority + Optional mechanistic study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Duroplasty<br>Duroplasty (includes Surgery with Laminectomy) | Procedure: Duroplasty<br>* Expansion Duroplasty<br>Procedure: Spinal surgery<br>* Spinal surgery including laminectomy<br>|
| Active Comparator: No duroplasty<br>No duroplasty (but includes surgery with Laminectomy) | Procedure: Spinal surgery<br>* Spinal surgery including laminectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AIS motor score | Change in American Spinal Injury Association Impairment Scale total limb motor score at 6 months | 6 months versus baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AIS light touch score | Change in American Spinal Injury Association Impairment Scale total light touch sensory score | 6 months versus baseline | 
| Change in AIS pin prick score | Change in American Spinal Injury Association Impairment Scale total pin prick sensory score | 6 months versus baseline | 
| Change in AIS grade | Change in American Spinal Injury Association grade | 6 months versus baseline | 
| CUE-Q | Capabilities of upper extremity-questionnaire (CUE-Q) | 6 months | 
| Grip strength | Hand grip strength assessed with dynamometer | 6 months | 
| WISCI II | Walking Index for Spinal Cord Injury version ii | 6 months | 
| SCIM III | Spinal Cord Independence Measure version III | 6 months | 
| SF-36 | Short Form survey 36 | 3 months, 6 months, 12 months | 
| Spinal re-operations | Number of reoperations on spine | 12 months | 
| Adverse events | Procedure Specific complications and adverse events | 12 months | 
| Mortality | Mortality | 12 months | 
| Length of hospital stay | Length of hospital stay | 12 months | 
| MRI | Magnetic resonance imaging of cervical spine | 2 weeks, 6 months | 
| Injury site physiology and metabolism (optional) | Optional mechanistic study: Mean daily intraspinal pressure, spinal cord perfusion pressure, tissue glucose, lactate, pyruvate, glycerol, glutamate, cytokines measured from the injury site | Up to 5 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Decompression, surgical; Neurosurgery; Paralysis