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Trial registered on ANZCTR


Registration number
ACTRN12616000016437
Ethics application status
Approved
Date submitted
22/12/2015
Date registered
13/01/2016
Date last updated
14/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pregabalin for dural puncture headache
Scientific title
Pregabalin for the management of post-dural puncture headache after unintentional dural puncture in obstetric patients: a randomised, double-blind, placebo-controlled trial
Secondary ID [1] 288213 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
headache 297122 0
Condition category
Condition code
Anaesthesiology 297358 297358 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Prophylactic administration of oral pregabalin capsule twice daily. Dose 75 mg/75 mg for 2 days then 75 mg/150 mg for 2 days
Arm 2: Prophylactic administration of oral plabebo capsules twice daily

Total number of study drug capsules consumed will be recorded
Intervention code [1] 293507 0
Prevention
Intervention code [2] 293508 0
Treatment: Drugs
Comparator / control treatment
Comparator is a placebo capsule matched for each 75 mg active drug capsule
Control group
Placebo

Outcomes
Primary outcome [1] 296910 0
Severity of headache as assessed by incidence of "severe' rating at presentation and by 0-72 hour area-under-curve 1-10 intensity score
Timepoint [1] 296910 0
At onset of post-dural puncture headache, if presents
Secondary outcome [1] 319680 0
Incidence of post-dural puncture headache, as determined by confirmation of clinical diagnosis by anaesthesiologist after patient reporting of headache or on questioning at daily clinical review or interview (for 4 days and again at one week after commencing study drug)
Timepoint [1] 319680 0
Within 4 days of accidental dural puncture

Eligibility
Key inclusion criteria

1. Obstetric women aged 18 years and over
2. An unintentional dural puncture at the time of epidural analgesia for labour and delivery, confirmed by observation of efflux of cerebrospinal fluid from the needle or catheter; by identification of CSF from an epidural catheter; or by positive test-dosing for subarachnoid placement.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria

1. Attempted postpartum prevention of PDPH using any therapy other than intrathecal epidural catheter placement, including prophylactic epidural blood patch.
2. Onset of PDPH prior to study drug administration
3. Renal impairment
4. Contraindication to use or exposure to pregabalin within past 72 hours
5. ASA 4 status
6. Women planning to breastfeed a premature baby
7. Concurrent administration of drugs that may possibly impact on the severity of PDPH, namely oral tablets of or intravenous caffeine, triptans, hydrocortisone, oral theophylline or intravenous aminophylline, epidural morphine.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization sequence for each site, stratified for size of epidural needle (16 vs 17 or 18 gauge)
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
Efficacy
Statistical methods / analysis
The primary endpoints are the severity of PDPH, as measured by the incidence in each group of a rating of ‘severe’ at 24 hours after commencing treatment; and the AUC 0-72 h for pain (headache) scores. Previous data suggests that approximately 70% of women will develop a PDPH after unintentional dural puncture with an epidural needle and 40% of women will rate their headache as severe initially.
Using the severity of pain as a primary endpoint will require a sample size of approx. 85 per group or total 170 to test for a 50% reduction in the treatment group. To allow for those who do not develop a PDPH (0.7 x N = 170) plus withdrawals and loss to follow-up, this will be increased to 150 per group (300 patients).
There are few data on AUC in this situation, but in different populations and using the drug as treatment, women start around the 7-8/10 and have reduced to 2-4/10 after 3-4 days of pregabalin. Based on women in the placebo group starting on pain scores of 8, reducing to 6 on day 2 and 4 on day 3, a rough estimation of 72 h AUC would be ~430 (8x24h + 6x24h + 4x24h). Using a conservative estimate of standard deviation ~340 (representing 80% AUC), the sample size of 300 women would have > 90% power to show a 30% reduction in 0-72 hour AUC PDPH score in the active treatment group and a one-quarter reduction in the need for epidural blood patch, assuming an incidence of 60% in the control group.

An intention to treat analysis will be performed. Descriptive statistics will be median, interquartile range (IQR) and range or mean (standard deviation [SD]) as appropriate and categorical outcomes will be summarized using frequency distributions. The Chi-square test or Fisher exact tests will be used for comparisons of categorical outcomes between groups. Comparisons of continuous outcomes between groups will be based on Mann-Whitney tests, assuming lack of normality. P-values of < 0.05 will be considered statistically significant.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/02/2016
Actual
9/07/2016
Date of last participant enrolment
Anticipated
29/02/2020
Actual
22/07/2016
Date of last data collection
Anticipated
6/03/2020
Actual
29/07/2016
Sample size
Target
300
Accrual to date
Final
2
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 4989 0
King Edward Memorial Hospital - Subiaco
Recruitment postcode(s) [1] 12476 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 7485 0
United States of America
State/province [1] 7485 0
North Carolina

Funding & Sponsors
Funding source category [1] 292600 0
Charities/Societies/Foundations
Name [1] 292600 0
ANZCA Foundation
Country [1] 292600 0
Australia
Primary sponsor type
Hospital
Name
King Edward Memorial Hospital for Women
Address
374 Bagot Rd, Subiaco WA 6008
Country
Australia
Secondary sponsor category [1] 291317 0
None
Name [1] 291317 0
Address [1] 291317 0
Country [1] 291317 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294081 0
Women and Newborn Health Service
Ethics committee address [1] 294081 0
374 Bagot Rd Subiaco WA 6008
Ethics committee country [1] 294081 0
Australia
Date submitted for ethics approval [1] 294081 0
12/06/2015
Approval date [1] 294081 0
04/08/2015
Ethics approval number [1] 294081 0
2015132EW

Summary
Brief summary
The aim of this study is to investigate the efficacy of pregabalin against headache resulting from unintentional dural puncture in obstetric patients having epidural analgesia for labour and delivery.
The primary question addressed is “Does pregabalin reduce the severity of post-dural puncture headache in postpartum women after unintentional dural puncture?” Our hypothesis is that oral pregabalin will significantly reduce the severity of post-dural puncture headache in postpartum women experiencing the complication of unintentional dural puncture. The question is addressed by conduct of a randomized, double-blind, placebo-controlled, parallel-group, superiority clinical trial. The study drugs will be commenced after unintentional dural puncture and patients followed for one week, with the incidence and severity of headache important outcomes showing whether pregablin is effective compared with a placebo.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62378 0
Prof Michael Paech
Address 62378 0
Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, 374 Bagot Rd., Subiaco WA 6008
Country 62378 0
Australia
Phone 62378 0
+61893402222
Fax 62378 0
+61893402227
Email 62378 0
[email protected]
Contact person for public queries
Name 62379 0
Michael Paech
Address 62379 0
Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, 374 Bagot Rd., Subiaco WA 6008
Country 62379 0
Australia
Phone 62379 0
+61893402222
Fax 62379 0
+61893402227
Email 62379 0
[email protected]
Contact person for scientific queries
Name 62380 0
Michael Paech
Address 62380 0
Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, 374 Bagot Rd., Subiaco WA 6008
Country 62380 0
Australia
Phone 62380 0
+61893402222
Fax 62380 0
+61893402227
Email 62380 0
[email protected]

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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