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Trial registered on ANZCTR


Registration number
ACTRN12616001086459
Ethics application status
Approved
Date submitted
4/08/2016
Date registered
11/08/2016
Date last updated
10/06/2021
Date data sharing statement initially provided
10/06/2021
Date results information initially provided
10/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and feasibility of Immediate Cooling and Emergency Decompression (ICED) for cervical spinal cord injuries
Scientific title
Immediate Cooling and Emergency Decompression (ICED) in Traumatic Cervical Spinal Cord Injury - A Safety and Feasibility study
Secondary ID [1] 289753 0
Nil
Universal Trial Number (UTN)
Trial acronym
ICED- Immediate Cooling and Emergency Decompression
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic Cervical Spinal Cord Injury 299600 0
Traumatic Central Cord Syndrome 299601 0
Condition category
Condition code
Neurological 299570 299570 0 0
Other neurological disorders
Injuries and Accidents 299571 299571 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with cervical spinal cord injury (SCI) will be cooled by paramedics using ice-cold intravenous saline to a target core temperature of 33-34 degrees Celsius. Cooling will be continued in hospital using an intravascular cooling catheter (or surface temperature management system) set to maintain the target temperature of 33-34 degrees Celsius. The cooling method selected in hospital will be chosen at the discretion of the treating physician.

Patients will be maintained at the target temperature (33.0-34.0 degrees Celsius) for 24 hours post-treatment initiation and then slowly rewarmed to 36 degrees Celsius over 12 hours. Controlled temperature management (36-37 degrees Celsius) will be continued for a further 72 hours. Patients enrolled in the trial will be admitted to the Intensive Care Unit (ICU) and core temperature recorded hourly across the period of therapy. Measures to control core temperature will be documented, including volume and duration of ice-cold saline infused, temperature management system selected, intensity and duration of temperature control and use of passive surface cooling measures.

Patients will also undergo decompression surgery as appropriate within 8 hours of injury for cervical fracture and/or dislocation injuries, and within 18 hours of injury for acute central cord syndrome. The aim of decompression will be to restore the spinal canal diameter to normal by reducing the dislocated vertebrae and removal of bone fragments, disc and other material. decision of whether surgery is required, Specifics including the number of levels decompressed, approach (anterior vs. posterior) and use of instrumentation will be left to the treating orthopaedic surgeons and/or neurosurgeons. Procedure duration averages between 2 and 4 hours and varies depending upon the extent of injury.
Intervention code [1] 295399 0
Treatment: Other
Intervention code [2] 295540 0
Treatment: Surgery
Comparator / control treatment
Study data will be compared to historical injuries and concurrent patients with cervical SCI treated at the Alfred Hospital since 2010. Control patient information will be collected by retrospective medical record review.
Control group
Historical

Outcomes
Primary outcome [1] 299046 0
Proportion of patients with vertebral fracture and/or dislocation injuries undergoing decompression within 8 hours following acute cervical SCI, will be assessed by medical record review.
Timepoint [1] 299046 0
8 hours post-injury
Primary outcome [2] 299047 0
Proportion of patients with acute central cord syndrome undergoing decompression within 18 hours following injury, will be assessed by medical record review.
Timepoint [2] 299047 0
18 hours post-injury
Secondary outcome [1] 325990 0
Proportion of patients achieving decompression within target time frames and hypothermia as per protocol will be assessed by medical record review.
Timepoint [1] 325990 0
24 hours post-injury
Secondary outcome [2] 325991 0
Proportion of patients achieving target core temperature 33-34 degrees Celsius will be assessed by medical record review.
Timepoint [2] 325991 0
Time patient temperature reaches 33-34 degrees Celsius
Secondary outcome [3] 325992 0
Time from injury to 35.0 degrees Celsius or below will be assessed by medical record review
Timepoint [3] 325992 0
Time patient temperature reaches 35.0 degrees Celsius or below
Secondary outcome [4] 325993 0
Time from injury to the target core temperature of 33-34 degrees Celsius will be assessed by medical record review.
Timepoint [4] 325993 0
Time patient reaches target core temperature of 33-34 degrees Celsius
Secondary outcome [5] 325994 0
Temperature profile over the period of cooling and temperature management. Core temperature will be monitored by a thermistor within the intravascular catheter. If cooling is performed using a surface temperature management system, a bladder thermometer will be used to monitor core temperature.
Timepoint [5] 325994 0
Hourly measurements of temperature from initiation of cooling through to the end of temperature controlled management
Secondary outcome [6] 325995 0
Temperature reduction achieved by paramedics will be assessed by medical record review.
Timepoint [6] 325995 0
From time of paramedic initiation of cooling until patient admission to hospital.
Secondary outcome [7] 325996 0
Time of initiation of cooling by paramedics will be assessed by medical record review.
Timepoint [7] 325996 0
From time of paramedic initiation of cooling until patient admission to hospital.
Secondary outcome [8] 325997 0
The incidence of moderate and severe pneumonia within 14 days of injury will be assessed by medical record review.
Timepoint [8] 325997 0
From initiation of cooling until 14 days post-injury
Secondary outcome [9] 325998 0
The incidence of other respiratory complications, for example pulmonary oedema (fluid accumulation in the lungs), and atelectasis (partial lung collapse), will be assessed clinically using defined criteria and by imaging including chest X-ray and chest CT where necessary. The incidence of adverse events such as urinary tract infection or surgical site infection will be assessed clinically using defined criteria and pathology testing of blood/urine/sputum samples.
Timepoint [9] 325998 0
From initiation of cooling until 6 months post-injury (+/- 1 month)
Secondary outcome [10] 325999 0
Incidence of shivering and need for anti-shivering measures will be assessed by medical record review
Timepoint [10] 325999 0
From initiation of cooling until the end of temperature controlled management
Secondary outcome [11] 326000 0
The incidence of administration of Fresh Frozen Plasma, Cryoprecipitate or Prothrombin X will be assessed by medical record review.
Timepoint [11] 326000 0
Period of hospital admission
Secondary outcome [12] 326001 0
Length of intubation will be assessed by medical record review
Timepoint [12] 326001 0
Period from intubation until extubation
Secondary outcome [13] 326002 0
ICU length of stay will be assessed by medical record review
Timepoint [13] 326002 0
Period of ICU admission until discharge
Secondary outcome [14] 326003 0
International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) grading of injury and motor score will be performed by a trained assessor.
Timepoint [14] 326003 0
6 months post-injury (+/- 1 month)
Secondary outcome [15] 326004 0
Spinal Cord Independence Measure (SCIM) questionnaire (self-care and mobility sections only)
Timepoint [15] 326004 0
6 months post-injury (+/- 1 month)
Secondary outcome [16] 326005 0
Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) test of grip strength and prehension
Timepoint [16] 326005 0
6 months post-injury (+/- 1 month)
Secondary outcome [17] 326006 0
Lower limb motor function will be assessed using the 10-meter walk test
Timepoint [17] 326006 0
6 months post-injury (+/- 1 month)
Secondary outcome [18] 326101 0
Grip strength (myometry)
Timepoint [18] 326101 0
6 months post-injury (+/- 1 month)
Secondary outcome [19] 326584 0
The volume of fluid infused by paramedics will be assessed by medical record review.
Timepoint [19] 326584 0
From time of paramedic initiation of cooling until patient admission to hospital.

Eligibility
Key inclusion criteria
Cervical vertebral column trauma
Less than 2 hours post-injury
Able to participate in the Spinal Emergency Evaluation of Deficits (SPEED) neurological assessment
Neurological deficits in all 4 limbs: Flicker or no ankle or toe movement bilaterally (SPEED motor score of 0-2) and weak or no hand grip on SPEED neurological assessment
Planned transport to the participating study hospital

Additional criterion for potential central cord syndrome patients: Less than 4 hours post-injury with definite foot movement (SPEED motor of 2-4), weak or no hand movement and American Spinal Injury Association Impairment Scale (AIS) motor examination score less than or equal to 50/100
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to commence induction of hypothermia within 2 hours post-injury (or within 4 hours post-injury for central cord syndrome patients)
Unable to follow commands due to significant head injury, drug or alcohol intoxication, mental or hearing impairment
Glasgow coma score <13
Suspected multiple traumatic injuries with significant blood loss (due to likely trauma to the chest, abdomen, pelvis or long bone fractures)
Known or obvious pregnancy
Cardiac arrest at scene
Pre-injury major neurological deficit (e.g. stroke, Parkinson’s disease or dementia)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Fisher’s exact test will be used to analyse the primary outcome and to detect differences in the proportion of hypothermic patients. Fisher’s exact test will also be used to detect differences in the proportion of patients experiencing respiratory and other complications. Continuous measures will be compared by analysis of variance (ANOVA) with Tukey HSD (honestly significant difference) post-hoc error correction. Six-month outcomes will be compared by ANOVA with Tukey HSD post-hoc error correction for continuous measures and the Kruskal-Wallis test for ranked data.

Sample size was calculated using historical data of 8% of patients with vertebral fracture and/or dislocation injuries undergo decompression within 8 hours following injury, while 6% of patients with acute central cord syndrome undergo decompression within 18 hours following injury (Victorian data). To determine the feasibility of undertaking early surgery in 80% of patients within these time frames, 9 patients with cervical spinal cord injury as a result vertebral fracture and/or dislocation injuries and 9 patients with acute central cord injuries will be required for adequate statistical power (using Fisher’s exact test to detect a difference in proportion between 8% and 80%, a=0.05 and beta=0.2).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2016
Actual
10/04/2017
Date of last participant enrolment
Anticipated
2/11/2019
Actual
10/02/2019
Date of last data collection
Anticipated
Actual
18/03/2020
Sample size
Target
18
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 6268 0
The Alfred - Prahran
Recruitment postcode(s) [1] 13704 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 294148 0
Government body
Name [1] 294148 0
NHMRC
Country [1] 294148 0
Australia
Funding source category [2] 294149 0
Government body
Name [2] 294149 0
Institute for Safety, Compensation and Recovery Research (ISCRR)
Country [2] 294149 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Parkville, VIC 3010
Country
Australia
Secondary sponsor category [1] 292979 0
None
Name [1] 292979 0
Address [1] 292979 0
Country [1] 292979 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295559 0
Alfred Health Human Research Ethics Committee
Ethics committee address [1] 295559 0
55 Commercial Rd, Melbourne, VIC 3004
Ethics committee country [1] 295559 0
Australia
Date submitted for ethics approval [1] 295559 0
03/08/2016
Approval date [1] 295559 0
22/12/2016
Ethics approval number [1] 295559 0

Summary
Brief summary
In young patients, traumatic injury to the cervical spinal cord generally results from vertebral fracture and dislocation of vertebra, with injury to the spinal cord occurring not just at the time of impact, but also from compression of the spinal cord as a consequence of the displaced vertebra. Traumatic central cord syndrome differs from traumatic SCI in that the general mechanism is hyper-extension of the spine, causing acute severe canal restriction, in a patient with pre-existing narrowing of the cervical canal. Compression of the spinal cord as a result of canal stenosis and cord swelling usually occurs soon after injury.
Animal and preliminary human data demonstrate that urgent relief of compression appears to greatly improve outcome. However, urgent decompression in humans is difficult to achieve because of the time occupied by transportation, investigation, and stabilisation of the patient as well as the organisation of surgery. Pre-clinical data demonstrate that hypothermia can suspend the progressive damage caused to the spinal cord by compression thereby allowing decompressive surgery to be performed in a clinically achievable time frame (Batchelor et al. 2010).

The primary purpose of the ICED study is to determine whether the combination of hypothermia and early decompression is able to improve outcomes in patients with severe spinal cord injuries of the neck. Selected patients will be cooled by paramedics or emergency physicians immediately following injury and then rapidly transported to theatre to undergo surgical decompression and stabilisation of the spinal cord. Cooling will be maintained for 24 hours and then patients will be slowly rewarmed and monitored over the next 72 hours.

The ICED safety and feasibility study will determine whether it is possible to cool patients with spinal cord injuries resulting from vertebral trauma in the neck in the first hours after injury. This study will also determine whether it is feasible to operate on patients very early after injury. As well as determining whether these interventions can be performed, the incidence and severity of complications will be monitored to determine whether these interventions are safe.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67678 0
Dr Peter Batchelor
Address 67678 0
Level 6, Alfred Centre, 99 Commercial Road Melbourne VIC 3004
Country 67678 0
Australia
Phone 67678 0
+61 3 9903 0884
Fax 67678 0
Email 67678 0
[email protected]
Contact person for public queries
Name 67679 0
Peter Batchelor
Address 67679 0
Level 6, Alfred Centre, 99 Commercial Road Melbourne VIC 3004
Country 67679 0
Australia
Phone 67679 0
+61 3 9903 0884
Fax 67679 0
Email 67679 0
[email protected]
Contact person for scientific queries
Name 67680 0
Peter Batchelor
Address 67680 0
Level 6, Alfred Centre, 99 Commercial Road Melbourne VIC 3004
Country 67680 0
Australia
Phone 67680 0
+61 3 9903 0884
Fax 67680 0
Email 67680 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Other filesNo Australian & New Zealand Spinal Cord Society Annua... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseImmediate Cooling and Early Decompression for the Treatment of Cervical Spinal Cord Injury: A Safety and Feasibility Study.2023https://dx.doi.org/10.1089/ther.2022.0046
N.B. These documents automatically identified may not have been verified by the study sponsor.