Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000428167p
Ethics application status
Submitted, not yet approved
Date submitted
28/02/2019
Date registered
15/03/2019
Date last updated
15/03/2019
Date data sharing statement initially provided
15/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Can a painkiller for nerve damage (pregabalin) prevent chronic pain after open heart surgery?
Scientific title
Pregabalin for the prevention of chronic pain after cardiac surgery: a randomised, double-blind, placebo-controlled trial
Secondary ID [1] 296680 0
None
Universal Trial Number (UTN)
Trial acronym
PRACS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic post-surgical pain 310540 0
Condition category
Condition code
Anaesthesiology 309250 309250 0 0
Pain management
Surgery 309251 309251 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pregabalin (oral)
150mg capsule 2 hours before surgery
75mg capsule 12-hourly for 48 hours after surgery

Medication to be administered under direct observation by treating nurse
Intervention code [1] 313007 0
Treatment: Drugs
Comparator / control treatment
Matching placebo (oral)
Placebo before surgery
Placebo 12-hourly for 48 hours after surgery

Placebo composed of microcrystalline cellulose with gelatin capsule
Control group
Placebo

Outcomes
Primary outcome [1] 308226 0
Chronic post-surgical pain (CPSP)

The incidence of CPSP will be reported by the patient at telephone follow-up. CPSP will be defined as pain experienced in the area of the index surgery, with onset after surgery, and persisting for 3 or more months. Presence of CPSP assessed via the Chronic Pain Grade (CPG) questionnaire.
Timepoint [1] 308226 0
3 months post-surgery (primary timepoint)
6 months post-surgery
Secondary outcome [1] 354289 0
Analgesic use

Type, dose, route and time of delivery to recorded. Opioids will be converted to morphine-equivalent units.
Inpatient analgesic use to be assessed via patient medication charts.
Outpatient analgesic use to be assessed via study-specific questionnaire completed by the patient.
Timepoint [1] 354289 0
Time of surgery to discharge, 3 and 6 months after surgery
Secondary outcome [2] 354290 0
Acute pain
Assessed using an 11-point numerical rating scale (0=no pain, 10=worst possible pain).
Timepoint [2] 354290 0
Every 4-8 hours from time of surgery to discharge
Secondary outcome [3] 354291 0
Sedation
Sedation is a common side-effect of pregabalin, it will be assessed using the Richmond Agitation-Sedation Scale (RASS) (Sessler et al., 2002).
Timepoint [3] 354291 0
Every 4-8 hours from time of surgery to discharge
Secondary outcome [4] 354294 0
Blood pressure

Assessed during surgery using anaesthetic observation chart
Assessed during hospital admission using inpatient observation chart
Timepoint [4] 354294 0
During surgery and time of surgery to discharge
Secondary outcome [5] 354295 0
Nausea
Assessed on a 4-point scale (no/mild/moderate/severe nausea)
Timepoint [5] 354295 0
Every 4-8 hours from time of surgery to discharge
Secondary outcome [6] 354296 0
Dizziness
Assessed on a 4-point scale (no/mild/moderate/severe nausea)
Timepoint [6] 354296 0
Every 4-8 hours from time of surgery to discharge
Secondary outcome [7] 354303 0
Confusion
Confusion is a common side-effect of pregabalin, it will be assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) (Ely et al., 2001).
Timepoint [7] 354303 0
Every 4-8 hours from time of surgery to discharge
Secondary outcome [8] 368030 0
Heart rate

Assessed during surgery using anaesthetic observation chart
Assessed during hospital admission using inpatient observation chart
Timepoint [8] 368030 0
During surgery and time of surgery to discharge

Eligibility
Key inclusion criteria
All adult patients undergoing open-cardiac surgery via sternotomy (e.g. coronary artery bypass grafting, valve replacement)
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Salvage surgery;
Endovascular surgery;
Patients receiving renal dialysis;
Patients taking antiepileptic agents;
Patients taking chronic opioids or non-steroidal anti-inflammatory drugs (NSAIDs);
Patients taking psychotropic medications for a known chronic psychiatric condition;
Patients with Parkinson’s disease; and
Patients with dementia (diagnosed reduction in cognitive function).

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)
Randomisation using sealed opaque envelopes
Allocation schedule held off-site by third-party (Monash Health clinical trials)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated randomisation sequence
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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The proposed sample size for this study is 200 patients with 100 in each arm. Four recent studies report the incidence of chronic postoperative pain after cardiac surgery between 35.3-43.0% with a cumulative incidence rate (2071 patients) of 40%.

We calculated that 81 patients in each group, 162 in total, are required to achieve a clinically significant reduction in the incidence of chronic postoperative pain from 40% to 20% on the Chronic Pain Grade questionnaire (grade 0 = no pain, grade I-IV = chronic pain). All calculations are based on an 80% chance of detecting a difference at the 5% level of significance (power= 0.8, a=0.05). Accounting for a 20% (n=32) attrition rate at the 3-month mark, we determined that 200 patients are necessary to detect a statistically significant difference.

Results will be analysed after data extraction with dedicated statistical software (GraphPad Prism 8, MedCalc 18, SPSS 23). Data will be expressed as frequencies, percentages, mean ± SD and median (range), as indicated. The D’Agostino-Pearson test will be used to evaluate the normal distribution of continuous variables. Unpaired Student’s T, Mann-Whitney U, Chi-squared or Fisher’s exact test will be used where appropriate to identify differences between the groups for continuous or categorical variables. Subgroup analysis for duration of anaesthesia and different types of surgical procedures will be conducted.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2019
Actual
Date of last participant enrolment
Anticipated
1/04/2020
Actual
Date of last data collection
Anticipated
1/10/2020
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12518 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 24899 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 301259 0
Hospital
Name [1] 301259 0
Department of Anaesthesia and Department of Critical Care, Monash Health
Country [1] 301259 0
Australia
Primary sponsor type
Individual
Name
Professor Yahya Shehabi
Address
School of Clinical Sciences at Monash Health
Level 5, E Block, Monash Medical Centre
246 Clayton Road
Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 300917 0
None
Name [1] 300917 0
Address [1] 300917 0
Country [1] 300917 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 302000 0
Monash Health HREC
Ethics committee address [1] 302000 0
Research Support Services
Level 2, i Block,
Monash Medical Centre
246 Clayton Road
CLAYTON VIC 3168
Ethics committee country [1] 302000 0
Australia
Date submitted for ethics approval [1] 302000 0
14/11/2018
Approval date [1] 302000 0
Ethics approval number [1] 302000 0

Summary
Brief summary
Chronic pain (3 months) occurs in up to two-thirds of patients after open-cardiac surgery. This is predominantly neuropathic pain; a consequence of nerve damage during instrumentation. Previous studies have shown pregabalin effectively reduces acute pain after cardiac surgery. There is, however, a lack of research regarding chronic pain.

The PRACS (pregabalin for the prevention of chronic pain after open-cardiac surgery) trial aims to reduce chronic pain and improve quality of life for cardiac patients. This randomised, double-blind, placebo-controlled trial is a collaboration between anaesthetics, ICU and cardiothoracic surgery at Monash Medical Centre. We aim commence the trial in early 2019 with a target sample of 200 patients. The intervention group will receive active pregabalin (150mg before surgery and 75mg 12-hourly for 48 hours after surgery) while the control group will receive matching placebo. Participants will be monitored in hospital and at the 3 and 6 month mark
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88814 0
Prof Yahya Shehabi
Address 88814 0
School of Clinical Sciences at Monash Health
Level 5, E Block, Monash Medical Centre
246 Clayton Road
Clayton VIC 3168
Country 88814 0
Australia
Phone 88814 0
+613 9594 5610
Fax 88814 0
Email 88814 0
[email protected]
Contact person for public queries
Name 88815 0
Prof Yahya Shehabi
Address 88815 0
School of Clinical Sciences at Monash Health
Level 5, E Block, Monash Medical Centre
246 Clayton Road
Clayton VIC 3168
Country 88815 0
Australia
Phone 88815 0
+613 9594 5610
Fax 88815 0
Email 88815 0
[email protected]
Contact person for scientific queries
Name 88816 0
Prof Yahya Shehabi
Address 88816 0
School of Clinical Sciences at Monash Health
Level 5, E Block, Monash Medical Centre
246 Clayton Road
Clayton VIC 3168
Country 88816 0
Australia
Phone 88816 0
+613 9594 5610
Fax 88816 0
Email 88816 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
n line with our ethics approval, participant data will be made anonymous and will be aggregated for the purpose of statistical analyses. Findings will be reported at the group/condition level rather than the individual participant level.


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.