Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000447651
Ethics application status
Approved
Date submitted
28/03/2014
Date registered
30/04/2014
Date last updated
26/10/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Transfer of gabapentin and pregabalin in to breast milk
Scientific title
In lactating women immediately post delivery, when given a single dose of gabapentin or pregabalin, how much drug transfers in to breast milk?
Secondary ID [1] 284046 0
Nil
Universal Trial Number (UTN)
Trial acronym
GRAB-MILK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
1. To describe the transfer of gabapentin and pregabalin in to breast milk in lactating women immediately post-partum. 291103 0
Condition category
Condition code
Reproductive Health and Childbirth 291445 291445 0 0
Breast feeding
Anaesthesiology 291993 291993 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will look at the transfer of gabapentin and pregabalin in to the breast milk of women who will not be breastfeeding in the immediate post-partum period (days 1-4 following childbirth).

Arm 1: participants assigned to receive an oral dose of gabapentin 300mg will have drug levels measured from one venous blood sample and four breast milk samples over the subsequent 24 hours.

Arm 2: participants assigned to receive an oral dose of pregabalin 150mg will have drug levels measured from one venous blood sample and four breast milk samples over the subsequent 24 hours.

The assigned drug will be administered at 07.00am with venous and breast milk samples taken over the subsequent 24 hours. The assigned drug may be administered on any one of the days 1-4 following childbirth).
Intervention code [1] 288739 0
Treatment: Drugs
Comparator / control treatment
There are two separate groups being evaluated (gabapentin and pregabalin) but there will be no comparison made between these two groups (ie. there is no "active control")
There is no inactive control group.
The study is an uncontrolled single group trial for gabapentin and an uncontrolled single group trial for pregabalin being done in parallel.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291428 0
Quantitative analysis of gabapentin and pregabalin levels in breast milk and maternal plasma for pharmacokinetic modelling.
Timepoint [1] 291428 0
Analysis will occur on four breast milk samples over the 24 hours following drug administration (the four samples will be randomly selected from eight possible time periods: 0.5-1 hour, 1-2 hours, 2-4 hours, 4-6 hours, 6-9 hours, 9-12 hours, 12-18 hours, 18-24 hours). One maternal plasma sample will be randomly allocated to coincide with a breast milk sample to provide a milk:plasma ratio.
Secondary outcome [1] 306748 0
nil
Timepoint [1] 306748 0
nil

Eligibility
Key inclusion criteria
1. ASA 1 or 2
2. Post-partum
3. Not planning to breast feed or unable to breast feed initially (eg unwell neonate)
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Current use of other neuropathic analgesia or anti-epileptic drugs.
2. Contraindication to either study medication (eg obstructive sleep apnoea)
3. History of epilepsy
4. Severe pre-eclampsia with renal impairment

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)
Women delivering at the King Edward Memorial Hospital, but who will not be breast feeding in the immediate post-partum period, will be invited to participate in the study.
Those that meet the relevant inclusion/exclusion criteria and consent to particpation in the study will be assigned to receive a single dose of either gabapentin or pregabalin. Allocation to the gabapentin or pregabalin group will be unblinded as there is no control group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
Simulations within NONMEM (non-linear mixed effects modelling) were used to determine the study sample size of 80 particpants (40 participants assigned to each arm). Pharmacokinetic data on gabapentin and pregabalin were used in these simulations with an expected milk to plasma ratio = 1.

Measured data will be analysed using population pharmacokinetic methods within NONMEN - this will allow estimates to be made of the absolute and relative infant dose.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2016
Actual
Date of last participant enrolment
Anticipated
1/01/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 2057 0
King Edward Memorial Hospital - Subiaco
Recruitment postcode(s) [1] 7753 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 288674 0
Charities/Societies/Foundations
Name [1] 288674 0
Australia and New Zealand College of Anaesthetists Research Grant
Country [1] 288674 0
Australia
Primary sponsor type
Hospital
Name
King Edward Memorial Hospital
Address
374 Bagot Rd
Subiaco WA 6008
Country
Australia
Secondary sponsor category [1] 287382 0
None
Name [1] 287382 0
Address [1] 287382 0
Country [1] 287382 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290524 0
Womens and Newborn Health Service Ethics Committee
Ethics committee address [1] 290524 0
Ethics Office
Level 1
Children's Clinical Research Facility
Princess Margaret Hospital
GPO Box D184
Perth WA 6840
Ethics committee country [1] 290524 0
Australia
Date submitted for ethics approval [1] 290524 0
17/02/2014
Approval date [1] 290524 0
11/08/2014
Ethics approval number [1] 290524 0

Summary
Brief summary
Gabapentin and pregabalin are anticonvulsants used in the management of both acute and chronic pain. They offer a potentially useful analgesic adjunct to women in the
post-partum period. However, there is limited information about the transfer of these drugs in to breast milk which has lead to safety concerns over their use in breastfeeding mothers.

By assigning post-partum mothers not intending to breastfeed to receive a dose of either gabapentin or pregabalin, measurements of plasma and breast milk concentrations can be made without risk of drug transfer to the newborn.

This data will then be used to create pharmacokinetic models to estimate absolute and relative infant doses if used in breastfeeding mothers.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 46086 0
A/Prof Nolan McDonnell
Address 46086 0
Department of Anaesthesia
King Edward Memorial Hospital
374 Bagot Rd
Subiaco WA 6008
Country 46086 0
Australia
Phone 46086 0
+61 8 93402222
Fax 46086 0
Email 46086 0
[email protected]
Contact person for public queries
Name 46087 0
A/Prof Nolan McDonnell
Address 46087 0
Department of Anaesthesia
King Edward Memorial Hospital
374 Bagot Rd
Subiaco WA 6008
Country 46087 0
Australia
Phone 46087 0
+61 8 93402222
Fax 46087 0
Email 46087 0
[email protected]
Contact person for scientific queries
Name 46088 0
A/Prof Nolan McDonnell
Address 46088 0
Department of Anaesthesia
King Edward Memorial Hospital
374 Bagot Rd
Subiaco WA 6008
Country 46088 0
Australia
Phone 46088 0
+61 8 93402222
Fax 46088 0
Email 46088 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

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

Documents added automatically
No additional documents have been identified.