Clinical trial NCT04936620: Duroplasty for Injured Cervical Spinal Cord With Uncontrolled Swelling
Official title: Duroplasty for Injured Cervical Spinal Cord With Uncontrolled Swelling
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries
Keywords: Decompression, surgical; Neurosurgery; Paralysis
Lead sponsor: St George's, University of London
Sponsor class: OTHER
Collaborators: name: St George's University Hospitals NHS Foundation Trust
name: St. Mary's University, Twickenham
name: University of Bristol
name: Ohio State University
name: University of Cambridge
name: University of Oxford
name: Buckinghamshire Healthcare NHS Trust
First posted: 2021-06-23
Enrollment: 222
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase III clinical trial: randomised, controlled, double blind, multi-centre, superiority

+ Optional mechanistic study
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: Inclusion Criteria:

1. Age ≥16 years
2. Severe cervical (C2 - T1) traumatic spinal cord injury (AIS grade A-C)
3. Deemed to require and be suitable for surgery that includes laminectomy by local surgeon
4. Surgery within 72 hours of traumatic spinal cord injury
5. Able to provide informed consent or consultee declaration or proxy consent.

Exclusion Criteria:

1. Dural tear due to traumatic spinal cord injury
2. Life-limiting or rehabilitation-restricting co-morbidities
3. Thoracic or lumbar traumatic spinal cord injury
4. Other central nervous system disease

Primary outcomes:
measure: Change in AIS motor score
timeFrame: 6 months versus baseline
Secondary outcomes:
measure: Change in AIS light touch score
timeFrame: 6 months versus baseline
measure: Change in AIS pin prick score
timeFrame: 6 months versus baseline
measure: Change in AIS grade
timeFrame: 6 months versus baseline
measure: CUE-Q
timeFrame: 6 months
measure: Grip strength
timeFrame: 6 months
measure: WISCI II
timeFrame: 6 months
measure: SCIM III
timeFrame: 6 months
measure: SF-36
timeFrame: 3 months, 6 months, 12 months
measure: Spinal re-operations
timeFrame: 12 months
measure: Adverse events
timeFrame: 12 months
measure: Mortality
timeFrame: 12 months
measure: Length of hospital stay
timeFrame: 12 months
measure: MRI
timeFrame: 2 weeks, 6 months
measure: Injury site physiology and metabolism (optional)
timeFrame: Up to 5 days after surgery
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Universität Klinik für Neurochirurgie
city: Linz
country: Austria
facility: Kepler University Hospital
city: Salzburg
country: Austria
facility: University Hospital Salzburg
city: Leuven
country: Belgium
facility: UZ Leuven
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Frankfurt
country: Germany
facility: BG Unfallklinik Frankfurt am Main
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Centre
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
city: Madrid
country: Spain
facility: 12 de Octubre University Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Aylesbury
country: United Kingdom
facility: National Spinal Injuries Centre
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Liverpool
country: United Kingdom
facility: The Walton Centre
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: London
country: United Kingdom
facility: St Mary's Hospital
city: London
country: United Kingdom
facility: The London Spinal Cord Injury Centre
city: London
country: United Kingdom
facility: The Royal London Hospital
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
city: Oswestry
country: United Kingdom
facility: Midlands Centre for Spinal Injuries,
city: Salford
country: United Kingdom
facility: Salford Royal
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Southport
country: United Kingdom
facility: North West Regional Spinal Injuries Centre
city: Wakefield
country: United Kingdom
facility: Pinderfields Hospital
Study officials:
affiliation: St George's, University of London, U.K.
name: Marios C Papadopoulos
role: PRINCIPAL_INVESTIGATOR
affiliation: St George's, University of London, U.K.
name: Samira Saadoun
role: PRINCIPAL_INVESTIGATOR
References:
citation: Werndle MC, Saadoun S, Phang I, Czosnyka M, Varsos GV, Czosnyka ZH, Smielewski P, Jamous A, Bell BA, Zoumprouli A, Papadopoulos MC. Monitoring of spinal cord perfusion pressure in acute spinal cord injury: initial findings of the injured spinal cord pressure evaluation study*. Crit Care Med. 2014 Mar;42(3):646-55. doi: 10.1097/CCM.0000000000000028.
citation: Phang I, Werndle MC, Saadoun S, Varsos G, Czosnyka M, Zoumprouli A, Papadopoulos MC. Expansion duroplasty improves intraspinal pressure, spinal cord perfusion pressure, and vascular pressure reactivity index in patients with traumatic spinal cord injury: injured spinal cord pressure evaluation study. J Neurotrauma. 2015 Jun 15;32(12):865-74. doi: 10.1089/neu.2014.3668. Epub 2015 May 4.
citation: Phang I, Zoumprouli A, Papadopoulos MC, Saadoun S. Microdialysis to Optimize Cord Perfusion and Drug Delivery in Spinal Cord Injury. Ann Neurol. 2016 Oct;80(4):522-31. doi: 10.1002/ana.24750. Epub 2016 Aug 19.
citation: Saadoun S, Papadopoulos MC. Acute, Severe Traumatic Spinal Cord Injury: Monitoring from the Injury Site and Expansion Duraplasty. Neurosurg Clin N Am. 2021 Jul;32(3):365-376. doi: 10.1016/j.nec.2021.03.008. Epub 2021 May 7.