Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001175561
Ethics application status
Approved
Date submitted
14/10/2015
Date registered
2/11/2015
Date last updated
2/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of Pregabalin for peri-operative pain relief in arthroscopic or minimally invasive shoulder surgery – A randomised, double-blind, prospective clinical trial.
Scientific title
Efficacy of Pregabalin plus standard care peri-operative analgesia compared to standard care analgesia in patients aged between 35 and 75 years undergoing arthroscopic or minimally invasive shoulder surgery.
Secondary ID [1] 287472 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rotator cuff tear 296205 0
Condition category
Condition code
Anaesthesiology 296483 296483 0 0
Pain management
Surgery 296484 296484 0 0
Other surgery
Injuries and Accidents 296807 296807 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
75 mg of oral Pregabalin will be self-administered twice daily commencing 5 days before the participant's operation and continuing for 15 days after the operation including operation day. The trial participant receives a total of 42 doses of 75 mg Pregabalin over a total 21 days.

The Pregabalin will be delivered via the oral route in the form of a tablet (size and colour matched placebo will be used). Adherence to the dosing scheme will be monitored via Participant Diaries. These diaries will be checked at all visits (pre-op, operative, post-op).

Adherence to the dosing scheme will also be monitored via a 'calling plan.' Participants will be called 6, 3 and 1 day before their operation to check they are taking their medication appropriately. They will also be called 4, 8 and 12 days after their operation for the same reason. This plan helps to avoid the circumstance of an individual being excluded from the results due to poor compliance. A participant will be considered non compliant if they miss a total of 8 doses or if they miss 4 consecutive doses.
Intervention code [1] 293034 0
Treatment: Drugs
Comparator / control treatment
The control treatment is a placebo drug of the same appearance, colour and size as the Pregabalin drug. It will also be self-administered twice daily from 5 days pre-operation to 15 days post-operation for a total of 42 doses over 21 days.
Control group
Placebo

Outcomes
Primary outcome [1] 296326 0
The primary objective of this trial is to determine the effect of usual care analgesia plus 75 mg twice daily, oral Pregabalin for 5 days pre- and 15 days post-surgery when compared with usual care analgesia plus matching placebo. This comparison will be tested in the treatment of arthroscopic or minimally invasive shoulder surgery, in terms of average rest pain, measured by a VAS Pain score obtained 2 weeks post-operatively.
Timepoint [1] 296326 0
Two weeks post-operation
Secondary outcome [1] 318179 0
The secondary objectives of the trial are to test the effect of usual care analgesia plus 75 mg twice daily, oral Pregabalin for 5 days pre- and 15 days post-surgery when compared with usual care analgesia plus matching placebo, in the treatment of arthroscopic or minimally invasive shoulder surgery, as measured by the following:
VAS Pain score obtained for average pain
Timepoint [1] 318179 0
2, 6, and 12 hours post-operatively, twice daily from day 1 through to day 15 post-operatively, and 6 and 12 weeks post-operatively.
Secondary outcome [2] 318180 0
Oxford Shoulder Score (patient reported questionnaire designed to assess outcomes of surgery)
Timepoint [2] 318180 0
Obtained pre-operatively and at 2, 6, and 12 weeks post-operatively
Secondary outcome [3] 318181 0
Pain-Detect Questionnaire (patient reported questionnaire designed to detect neuropathic pain)
Timepoint [3] 318181 0
Obtained pre-operatively and 2, 6 and 12 weeks post-operatively.
Secondary outcome [4] 318182 0
Active and passive range of movement of the shoulder, measured as forward elevation, abduction, and external rotation of the shoulder using a goniometer. Internal rotation will be measured using a constant scoring based system. This is a composite secondary outcome - looking at the overall range of movement.
Timepoint [4] 318182 0
Obtained at baseline and at 2, 6 and 12 weeks post-operatively.
Secondary outcome [5] 318183 0
The amount of rescue medication (oral Endone in 5 mg doses) and the total intravenous opiate intake required. Total daily Endone doses for the first two post-operative weeks will also be recorded in participant diaries.
Timepoint [5] 318183 0
The first and second 12-hour post-operative periods as well as the total daily Endone doses for the first two post-operative weeks.
Secondary outcome [6] 318184 0
The recording of any side effects experienced (including nausea, dizziness, rash, sedation) in participant diaries
Timepoint [6] 318184 0
Duration of trial medication treatment (5 days pre-operative to 15 days post-operative)

Eligibility
Key inclusion criteria
Patients are eligible to be included in the trial only if they meet all of the following criteria:
[1] Present with a need for rotator cuff repair (for cuff tears diagnosed by ultra-sound or MRI scan) and/or subacromial decompression for impingement syndrome.
[2] Are aged between 35 and 75 years.
[3] Have an educational level and degree of understanding such that they can communicate intelligibly with the investigator and other trial personnel.
[4] Are judged to be reliable and agree to keep all appointments for clinic visits, tests and procedures required by the protocol.
[5] Are capable of giving informed consent.
Minimum age
35 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Patients will be excluded from the trial if they meet any of the following criteria:
[1] Are investigator site personnel directly affiliated with this trial and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. It will be the responsibility of the recruiting surgeon to gather this information and will obviously require trial participants cooperation.
[2] Are Epworth HealthCare employees.
[3] Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this trial.
[4] Are unwilling or unable to comply with the use of a data collection device to directly record data from the subject.
[5] Have massive, irreparable cuff tears. This will be a clinical decision made by the treating surgeon.
[6] Have peripheral neuropathy affecting the upper limbs.
[7] Chronic opiate use (defined as longer than 3 months use).
[8] Are pregnant, or are attempting to conceive.
[9] Have a diagnosed mental illness and are taking medication which may interfere with the trial.
[10] Are taking any anticonvulsant/anti-epileptic medication or have been diagnosed with epilepsy.
[11] Have a cognitive impairment, eg dementia.
[12] Inability to give informed consent.

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 will be concealed by computerised randomisation and generation of opaque numbered envelopes which will be secured in the hospital compounding pharmacy. Only pharmacy staff administering medication will be unblinded. The investigators conducting recruitment will allocate a trial number to be taken to the pharmacy for the random allocation of treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants who meet all criteria for enrolment will be randomised to double-blind treatment at Visit 1, using standard random permuted blocks. The Trial Biostatistician will create a spreadsheet with assignment for each trial participant number. The study coordinator will then be responsible for the physical formation of the trial envelopes, which will be kept within the compounding pharmacy. Therefore, the allocation of "Pregabalin" vs "Placebo" is randomised and each new participant is allocated the next available trial participant number.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size is based on the primary objective: to compare the efficacy of Pregabalin 75 mg twice daily plus standard care analgesia with that of standard care analgesia alone, on the change in pain severity from baseline to 2 weeks in terms of average rest pain two weeks post-operative, as measured on an VAS scale recorded in the participant’s diary.
In regard to the existing literature, Singla et al. (2015), found no statistically significant difference in average pain scores between Pregabalin 150mg and Placebo group, 72 hours post surgery (effect size equal to a difference between means of 0.04 of the pooled standard deviation). On the other hand, Jain et al. (2012), using a self-reported pain measure found an effect size of 1.50 standard deviation difference between Pregabalin and Placebo groups, although the sample sizes were small (20 per group) and so the results may not be typical. A recent review found general group differences to be of the order of half a standard deviation, and so in the interests of conservatism, an effect size of half a standard deviation difference between the post-test (14 days) means for the two groups would be expected. This effect size is equal to a “medium” difference according to the conventional criteria of Cohen (1998).
As specified below, the statistical analysis of pre-test and post-test data will be based on the ANCOVA framework. A statistical power analysis of ANCOVA was therefore performed using the method of Aberson (2010). Assuming no correlation between baseline and post-test (14 days) VAS Pain scores, (functionally equivalent to a simple independent samples t-test between the two treatment groups at post-test), and a 2 tailed p-value of 0.05, a sample size of 70 patients per group would lead to a power of 80%.

The Pearson correlation between baseline and post-test is herein assumed to be the same for both treatment groups. This assumption will be explicitly test for, but there is no clinical or theoretical reason why the correlations would be assumed to be different. As there is little theoretical reason for specifying a particular correlation, we employ the conventional criteria of Cohen (1998), with a baseline – post-test correlation of 0.10 being regarded as “small”, 0.30 as “medium” and 0.50 as “large”.

The power figures associated with these correlations would be 83.7%, 86.6% and 92.9% respectively. Allowing for 10% drop-out or attrition by two-weeks, the resulting figure of 77.8 (70/0.90) can be conservatively rounded to 80, therefore 80 participants per treatment group would be required.

Mean changes from baseline in efficacy measures will be analysed using analysis of covariance (ANCOVA) within a general regression framework such as the multilevel or generalized estimating equation approach to repeated measures. Fisher’s exact test will be used to compare the incidence of Serious Adverse Events, discontinuation due to adverse events and TEAEs in the two treatment groups.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
16/11/2015
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 4440 0
Epworth Richmond - Richmond

Funding & Sponsors
Funding source category [1] 292205 0
Other Collaborative groups
Name [1] 292205 0
Australian Orthopaedic Association
Country [1] 292205 0
Australia
Primary sponsor type
Hospital
Name
Epworth HealthCare
Address
89 Bridge Rd, Richmond VIC 3121
Country
Australia
Secondary sponsor category [1] 290881 0
None
Name [1] 290881 0
Address [1] 290881 0
Country [1] 290881 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293676 0
Epworth HealthCare Human Research Ethics Committee
Ethics committee address [1] 293676 0
Ethics committee country [1] 293676 0
Australia
Date submitted for ethics approval [1] 293676 0
10/07/2015
Approval date [1] 293676 0
05/08/2015
Ethics approval number [1] 293676 0
665-15

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

Contacts
Principal investigator
Name 60338 0
Dr Minoo Patel
Address 60338 0
The Epworth Centre, Suite 5.7
32 Erin Street, Richmond VIC 3121
Country 60338 0
Australia
Phone 60338 0
+61 03 94298084
Fax 60338 0
Email 60338 0
minoo.patel@bigpond.com
Contact person for public queries
Name 60339 0
Donna McCallum
Address 60339 0
Clinical Trials and Research Centre
185-187 Hoddle Street, Richmond VIC 3121
Country 60339 0
Australia
Phone 60339 0
+61 03 99368056
Fax 60339 0
Email 60339 0
donna.mccallum@epworth.org.au
Contact person for scientific queries
Name 60340 0
Minoo Patel
Address 60340 0
The Epworth Centre, Suite 5.7
32 Erin Street, Richmond VIC 3121
Country 60340 0
Australia
Phone 60340 0
+61 03 94298084
Fax 60340 0
Email 60340 0
minoo.patel@bigpond.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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