Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000557831
Ethics application status
Approved
Date submitted
22/09/2020
Date registered
12/05/2021
Date last updated
13/04/2022
Date data sharing statement initially provided
12/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial of dexmedetomidine compared to placebo to reduce pain after spinal fusion surgery
Scientific title
A randomised controlled trial of dexmedetomidine compared to placebo to reduce pain after spinal fusion surgery
Secondary ID [1] 301131 0
None
Universal Trial Number (UTN)
U1111-1258-5772
Trial acronym
The SPADE trial
Linked study record
Not applicable

Health condition
Health condition(s) or problem(s) studied:
Pain 317240 0
Spinal fusion surgery 317241 0
Condition category
Condition code
Anaesthesiology 315375 315375 0 0
Anaesthetics
Neurological 318261 318261 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dexmedetomidine by intravenous infusion started immediately after intubation, dosed as a loading dose of 0.5microg/kg over 10 minutes, followed by an infusion of 0.5microg/kg/hr ceased at the start of skin suturing (the functional end of the operation).

Protocol adherence will be audited in each case to ensure adequate compliance with the protocol.
Intervention code [1] 317439 0
Treatment: Drugs
Comparator / control treatment
0.9% NaCl placebo given by intravenous infusion, dosed as a loading dose of 0.5ml/kg over 10 minutes, followed by an infusion of 0.5ml/kg/hr ceased at the start of skin suturing (the functional end of the operation).
Control group
Placebo

Outcomes
Primary outcome [1] 323624 0
Pain, as reported by the patient using the Numerical Rating Scale (NRS)
Timepoint [1] 323624 0
At 1 hour after arriving in the Post Anaesthetic Care Unit
Secondary outcome [1] 382411 0
Patient-reported NRS pain score.
Timepoint [1] 382411 0
On admission to PACU, 24 hours after arrival to PACU. Also at 3 months after surgery via telephone call, the worst and best NRS over the past week as well as the NRS at the time of interview.
Secondary outcome [2] 382412 0
Total opioid dose in oral morphine equivalents. This outcome will be collected from the electronic medical record.
Timepoint [2] 382412 0
During anaesthesia and surgery
Secondary outcome [3] 382413 0
Total opioid dose in oral morphine equivalents. This outcome will be collected from the electronic medical record.
Timepoint [3] 382413 0
In the first 24 hours from arrival to PACU.
Secondary outcome [4] 382414 0
Postoperative disability measured using the WHODAS 2.0 score.
Timepoint [4] 382414 0
At 3 months post surgery (via telephone call)
Secondary outcome [5] 382415 0
Intra-operative side-effects after commencement of study drug:
i. Episode of bradycardia (HR <50 bpm), hypotension SBP <90 mmHg, or hypertension (SBP >90 mmHg) will be ascertained by audit of anaesthetic records via the hospital's electronic medical record that captures data directly from the anaesthetic machine at 20-second intervals.
Timepoint [5] 382415 0
During anaesthesia and surgery
Secondary outcome [6] 382416 0
i. Episode of bradycardia (HR <50 bpm), hypotension SBP <90 mmHg, or hypertension (SBP >90 mmHg) obtained by audit of the electronic medical record.
Timepoint [6] 382416 0
During the patient's stay in the post-anaesthetic care unit (PACU)
Secondary outcome [7] 382417 0
Episode of medical emergency team (MET) call triggered for first 24 hours post-operatively from arrival to PACU according to RMH policy.
Timepoint [7] 382417 0
In the first 24 post operative hours, obtained by audit of the electronic medical record.
Secondary outcome [8] 390713 0
ii. Use of vasopressors (e.g. metaraminol, ephedrine, noradrenaline, adrenaline) obtained by audit of the electronic medical record.
Timepoint [8] 390713 0
During anaesthesia and surgery
Secondary outcome [9] 390714 0
iii. Use of anticholinergics (e.g. atropine, glycopyrrolate) excluding when given with reversal of muscle relaxant obtained by audit of the electronic medical record.
Timepoint [9] 390714 0
During anaesthesia and surgery
Secondary outcome [10] 390715 0
iv. Cessation or reduction in study drug due to intra-operative bradycardia or hypotension obtained by audit of the electronic medical record.
Timepoint [10] 390715 0
During anaesthesia and surgery
Secondary outcome [11] 390716 0
ii. Episode of post-operative nausea or vomiting in PACU requiring antiemetic use obtained by audit of the electronic medical record.
Timepoint [11] 390716 0
During the patient's stay in PACU
Secondary outcome [12] 390717 0
iii. Episode of respiratory depression (RR less than 10 breaths/minute) in PACU obtained by audit of the electronic medical record.

Timepoint [12] 390717 0
During the patient's stay in PACU
Secondary outcome [13] 390718 0
iv. Use of rescue analgesic drugs in recovery (e.g. ketamine bolus/infusion) obtained by audit of the electronic medical record.
Timepoint [13] 390718 0
During the patient's stay in PACU
Secondary outcome [14] 395270 0
Time in PACU from admission until ready for discharge to the ward, assessed using timestamps from the Electronic Medical Record
Timepoint [14] 395270 0
During the patient's stay in PACU
Secondary outcome [15] 395271 0
Sedation, measured using the Modified Macintyre sedation score
Timepoint [15] 395271 0
On arrival to PACU and at 1 hour after arrival to PACU

Eligibility
Key inclusion criteria
• Adults 18 years and older having thoracic and/or lumbar spinal fusion surgery using a posterior approach.
• Anticipated to stay at least one post-operative night in hospital.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Unable or unwilling to provide consent or unable to communicate numerical rating scale pain score, including cognitively impaired, planned to remain on mechanical ventilation post-operatively or non-English speaking patients.
• Known diagnosis of significant cardiac conduction disease (second- or third-degree heart block, sick sinus syndrome, atrial fibrillation and atrial flutter) unless a pacemaker is present.
• Known diagnosis of severe ischemic heart disease, valvular heart disease or cardiomyopathy
• Known diagnosis of liver cirrhosis
• Bradycardia (heart rate (HR) < 50 bpm) in theatre suite before surgery
• Hypotension (systolic blood pressure (SBP) < 100 mmHg) in theatre suite before surgery
• Known diagnosis of allergy or hypersensitivity reactions to dexmedetomidine or any of the protocolised anaesthetic drugs.
• Previously enrolled into the SPADE study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will be by using sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The analysis sample will include all participants according to their randomised allocation (intention-to-treat). NRS pain will be analysed using a constrained longitudinal data analysis (cLDA) model assuming a common mean across groups on admission and a different mean for each group at each follow-up time point after arrival to PACU. The response will consist of all pain measurements (scores on admission to PACU, and at 1 hour, 24 hours and 3 months after arrival to PACU) and the model will include factors representing treatment, time (categorical), and treatment-by-time interaction, with the restriction of a common baseline mean across treatment groups. The mean change in NRS pain scores from admission to PACU to each time point after arrival to PACU between groups administered intraoperative dexmedetomidine infusion compared to standard practice will be obtained. The primary hypothesis will be evaluated by obtaining the estimated difference between dexmedetomidine and control groups in mean change in NRS pain score from admission to PACU to 1 hour after arrival to PACU, a two-sided 95% confidence interval and a p-value. Binary and continuous secondary outcomes will be analysed using logistic and linear regression models respectively.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/06/2021
Actual
24/05/2021
Date of last participant enrolment
Anticipated
30/06/2022
Actual
Date of last data collection
Anticipated
30/09/2022
Actual
Sample size
Target
128
Accrual to date
31
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 16577 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 30138 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 305571 0
Hospital
Name [1] 305571 0
The Royal Melbourne Hospital
Country [1] 305571 0
Australia
Primary sponsor type
Hospital
Name
The Royal Melbourne Hospital
Address
300 Grattan St,
Parkville, 3050
Victoria
Country
Australia
Secondary sponsor category [1] 305985 0
None
Name [1] 305985 0
Address [1] 305985 0
Country [1] 305985 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305875 0
Melbourne Health HREC
Ethics committee address [1] 305875 0
Ethics committee country [1] 305875 0
Australia
Date submitted for ethics approval [1] 305875 0
25/03/2020
Approval date [1] 305875 0
24/08/2020
Ethics approval number [1] 305875 0
HREC/61416/MH-2020

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101898 0
Dr Way-Siong (Alex) Koh
Address 101898 0
Department of Anaesthesia and Pain Management
The Royal Melbourne Hospital
300 Grattan St
Parkville 3050
Victoria
Country 101898 0
Australia
Phone 101898 0
+61393427540
Fax 101898 0
Email 101898 0
[email protected]
Contact person for public queries
Name 101899 0
Way-Siong (Alex) Koh
Address 101899 0
Department of Anaesthesia and Pain Management
The Royal Melbourne Hospital
300 Grattan St
Parkville 3050
Victoria
Country 101899 0
Australia
Phone 101899 0
+61 93427000
Fax 101899 0
Email 101899 0
[email protected]
Contact person for scientific queries
Name 101900 0
Way-Siong (Alex) Koh
Address 101900 0
Department of Anaesthesia and Pain Management
The Royal Melbourne Hospital
300 Grattan St
Parkville 3050
Victoria
Country 101900 0
Australia
Phone 101900 0
+61 393427000
Fax 101900 0
Email 101900 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
The authors are open to future proposals regarding data sharing, though while the ethical and legal ramifications of such arrangements remain unresolved the authors will not commit to this process. The authors look forward to the development of robust, widely-accepted agreements and protocols for data sharing emerging from highly resourced institutions and are open to adopting these protocols when they are settled.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.