Title: Duroplasty for Injured cervical Spinal Cord with Uncontrolled Swelling (DISCUS): a randomised controlled trial
Funder: Medical Research Council

Abstract: AIMS AND BACKGROUND: Acute traumatic spinal cord injury is a devastating condition that causes permanent disability (paralysis, numbness) and other complications such as chest and urine infections, pressure ulcers and loss of bladder and bowel control. In the UK, one person suffers a spinal cord injury every 8 hours and there are about 40,000 people living with long-term disabilities from cord injuries._x000D_ _x000D_ Currently, there are no treatments shown to benefit patients with spinal cord injuries. After the injury, the spinal cord swells and the pressure inside the cord rises, which obstructs the flow of blood to the injury site, causing further damage. Surgery aims to straighten and fix the spine with screws and rods to reduce pressure on the injured cord. Based on our research, we think that the tough membrane around the spinal cord (dura) is a major, but unappreciated, cause of cord pressure after injury. An operation called duroplasty involves opening the dura and stitching a patch of artificial dura to expand the space around the swollen spinal cord. We have shown in a small study of patients that performing this operation safely and effectively reduces pressure on the injured cord. A similar operation is routinely used to decompress the swollen brain after brain injury, but, for spinal cord injury, standard treatment is surgery on the spine without the duroplasty. In this study, we will investigate whether duroplasty helps improve patient outcomes after spinal cord injury. We predict that patients who had standard treatment plus duroplasty will have better outcomes than those who had standard treatment alone._x000D_ _x000D_ DESIGN AND METHODS: This is a randomised controlled trial. This means that those that agree to take part will be allocated by chance (like tossing a coin) to standard treatment or standard treatment plus duroplasty. Patients will not be aware which treatment they receive. The trial aims to recruit 222 patients aged 16 years or older, with severe spinal cord injuries in the neck from 26 NHS hospitals. Consent will be obtained from the patient or their family and surgery will be done as soon as possible (within 72 hours of injury). After agreeing to take part in the trial, patients will be asked to fill in questionnaires about their quality of life and will also be assessed on how well they can use their hands, walk and control their bladder and bowel. Some of these assessments will be repeated at 3, 6 and 12 months after surgery. These assessments will be combined with planned hospital visits and some questionnaires will be completed over the phone or by email. Some patients will also be asked to take part in a smaller study which involves placing probes at the injury site._x000D_ _x000D_ PATIENT AND PUBLIC INVOLVEMENT: This trial is focused on improving the quality of life of patients with spinal cord injuries and was designed with help from the Spinal Injuries Association and patients with spinal cord injuries. Two patient meetings were held to discuss the patient/family information sheet, consenting process and outcome measures. Patients with cord injuries will also be involved in the running of the trial._x000D_ _x000D_ DISSEMINATION: If this research shows there is a benefit to adding duroplasty to standard treatment, it is anticipated that duroplasty will become standard care for TSCI patients in the UK and, probably, internationally. Patients taking part in our research will be informed of the study findings via the Spinal Injuries Association.

Lay abstract: 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?_x000D_ _x000D_ 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. _x000D_ _x000D_ 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._x000D_ _x000D_ 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). _x000D_ _x000D_ 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. _x000D_ _x000D_ 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).

Research activity codes: 6.4 SURGERY
Health categories: INJURIES AND ACCIDENTS