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Trial registered on ANZCTR


Registration number
ACTRN12618001762246p
Ethics application status
Not yet submitted
Date submitted
21/10/2018
Date registered
25/10/2018
Date last updated
25/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pregabalin versus gabapentin in chronic neuropathic pain
Scientific title
A pilot series of n-of-1 randomised controlled trials to compare pregabalin and gabapentin in persistent neuropathic pain.
Secondary ID [1] 296379 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic neuropathic pain
310129 0
Condition category
Condition code
Anaesthesiology 308874 308874 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will undergo a 12-week trial comprising three 4-week treatment cycles. Each cycle will consist of a 2-week gabapentin block and a 2-week pregabalin block in an individually randomised order. During each block, participants will take their respective medication orally three times daily, with doses derived from the participant's existing neuropathic pain treatment dose. Throughout the trial, participants will complete a daily patient diary, reporting on relevant neuropathic pain symptoms such as daily pain, sleep interference, and functional limitation.

At the end of each block, participants will return their unused medications and finished patient diaries. After the 12-week trial, participants will complete a review appointment with their treating physician, in which the results of the trial will be presented to facilitate an informed and long-term treatment decision. Participants and physicians will additionally provide feedback on their experiences with the trial, as well as suggestions for further improvement.
Intervention code [1] 312716 0
Treatment: Drugs
Comparator / control treatment
In this trial, pregabalin will be compared against gabapentin in individual patients with neuropathic pain. There is no explicit control.
Control group
Active

Outcomes
Primary outcome [1] 307847 0
Difference in average pain intensity over the last 24 hours between each treatment block, as measured on a Visual Analogue Scale
Timepoint [1] 307847 0
At the end of each 4-week treatment cycle and at the end of the 12-week trial
Secondary outcome [1] 353142 0
Difference in sleep interference due to pain between each treatment block, as measured on a Visual Analogue Scale
Timepoint [1] 353142 0
At the end of each 4-week treatment cycle and at the end of the 12-week trial
Secondary outcome [2] 353143 0
Difference in functional ability between each treatment block, as measured by the Patient-Specific Function Scale
Timepoint [2] 353143 0
At the end of each 4-week treatment cycle and at the end of the 12-week trial
Secondary outcome [3] 353144 0
Difference in mental state between each treatment block, as measured by the Depression Anxiety Stress Scale 21
Timepoint [3] 353144 0
At the end of each 4-week treatment cycle and at the end of the 12-week trial
Secondary outcome [4] 353145 0
Patient's final medication preference (either pregabalin or gabapentin), as measured in binary form during the end-of-trial review
Timepoint [4] 353145 0
At the end of the 12-week trial
Secondary outcome [5] 353146 0
Feasibility composite outcome::
1) Enrolment rate, measured as participants enrolled per month
2) Proportion of screened patients able to be recruited for full trial
3) Patient compliance, assessed via unused medication counts and diary completion rates
4) Qualitative feedback regarding trial logistics and overall patient satisfaction, as collected from the patient and physician transcript during the end-of-trial review
Timepoint [5] 353146 0
At the end of the 12-week trial

Eligibility
Key inclusion criteria
1. Existing patient at Port Kembla Hospital
2. Age 18 years or greater
3. Existing diagnosis of chronic and stable neuropathic pain.
4. Currently prescribed gabapentin for neuropathic pain.
5. Willingness to maintain pain medications and treatments throughout the trial.
6. Capable English speaker
7. Able to be reliably contacted by telephone.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Currently breastfeeding or pregnant
2. Gabapentin or pregabalin allergy or intolerance
3. Active or past history of seizures
4. Creatinine clearance under 30 mL/min.
5. Likelihood of surgery during the trial
6. Inability to attend review visits

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)
Block randomization, with a block size of 2, will be used to generate random sequences for allocation to recruited participants. Randomization will be conducted by a statistician from the University of Queensland.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Crossover
Other design features
Phase
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Appropriate statistical analyses will be used to evaluate individual N-of-1 trial data. Data will also be aggregated from all trials to facilitate a meta-analysis of pregabalin versus gabapentin for neuropathic pain.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 12226 0
Port Kembla Hospital - Warrawong
Recruitment postcode(s) [1] 24405 0
2502 - Warrawong

Funding & Sponsors
Funding source category [1] 300986 0
Hospital
Name [1] 300986 0
Department of Rehabilitation Medicine, Port Kembla Hospital
Address [1] 300986 0
89-91 Cowper St, Warrawong, New South Wales 2502
Country [1] 300986 0
Australia
Primary sponsor type
Hospital
Name
Department of Rehabilitation Medicine Port Kembla Hospital
Address
89-91 Cowper St, Warrawong, New South Wales 2502
Country
Australia
Secondary sponsor category [1] 300571 0
None
Name [1] 300571 0
Address [1] 300571 0
Country [1] 300571 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 301746 0
Ethics committee address [1] 301746 0
Ethics committee country [1] 301746 0
Date submitted for ethics approval [1] 301746 0
01/01/2019
Approval date [1] 301746 0
Ethics approval number [1] 301746 0

Summary
Brief summary
Pregabalin and gabapentin are two medications commonly used to treat neuropathic pain. While both are moderately effective, there is significant variation between individuals, with patients often responding to one medication but not the other. N-of-1 trials are clinical trials that study a single patient, facilitating personalized data collection and reporting. We hypothesize that N-of-1 trials are a feasible method of comparing between pregabalin and gabapentin for individual patients with neuropathic pain.
Trial website
Trial related presentations / publications
Public notes
Gabapentin and Pregabalin are commonly used medications for neuropathic pain. They have similar mechanisms of action and adverse effects. In the Australian public health system, a significant cost differential exists between the two, with pregabalin being more expensive. The Illawarra-Shoalhaven Chronic Pain Service (I-SCPS) adopted strict open label prescribing criteria to limit Pregabalin to a second line medication, but this failed to prevent a rapid expansion in use. Head-to-head scientific evidence on this issue is of poor quality and contradictory. NICE recommendations for pregabalin use as first line are based on costings that are European based and dated. The local drug committee sought reassurance from the I-SCPS that clinical benefits were accruing from expenditure on Pregabalin over Gabapentin in individuals with neuropathic pain.

N-of-1 trials are randomized, double blind, multiple crossover trials in an individual patient. They help control for placebo effects, secondary effects, natural history, expectations of patients and clinicians, and the interactions of uncontrolled interventions such as over-the-counter medications in making a precise clinical decisions.

Contacts
Principal investigator
Name 87966 0
Dr Jane Nikles
Address 87966 0
University of Queensland Centre for Clinical Research
Building 71/918 RBWH Herston
Brisbane City QLD 4029
Country 87966 0
Australia
Phone 87966 0
+61 7 3374 3898
Fax 87966 0
Email 87966 0
catherine.nikles@uq.edu.au
Contact person for public queries
Name 87967 0
Dr Jane Nikles
Address 87967 0
University of Queensland Centre for Clinical Research
Building 71/918 RBWH Herston
Brisbane City QLD 4029
Country 87967 0
Australia
Phone 87967 0
+61 7 3374 3898
Fax 87967 0
Email 87967 0
catherine.nikles@uq.edu.au
Contact person for scientific queries
Name 87968 0
Dr Jane Nikles
Address 87968 0
University of Queensland Centre for Clinical Research
Building 71/918 RBWH Herston
Brisbane City QLD 4029
Country 87968 0
Australia
Phone 87968 0
+61 7 3374 3898
Fax 87968 0
Email 87968 0
catherine.nikles@uq.edu.au

No data has been provided for results reporting
Summary results
Not applicable