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Trial registered on ANZCTR


Registration number
ACTRN12620000203954
Ethics application status
Approved
Date submitted
27/01/2020
Date registered
20/02/2020
Date last updated
20/02/2020
Date data sharing statement initially provided
20/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Lignocaine for the prevention of chronic pain after caesarean section
Scientific title
Lignocaine for the prevention of chronic postsurgical pain in women undergoing caesarean section (Feasibility and safety study)
Secondary ID [1] 300367 0
None
Universal Trial Number (UTN)
U1111-1247-2893
Trial acronym
The I-Caesar Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
pregnancy 315980 0
postoperative pain 315981 0
chronic pain 315982 0
caesarean section 315983 0
Condition category
Condition code
Anaesthesiology 314259 314259 0 0
Pain management
Reproductive Health and Childbirth 314260 314260 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intravenous lignocaine: Women allocated to the intravenous lignocaine group (intervention group) will receive a lignocaine bolus of 1.0 mg/kg over 15 minutes followed by a lignocaine infusion of 1.5 mg/kg/hour (based on their current day of surgery weight). The bolus dose will commence immediately after the spinal anaesthetic injection at the same time as the prophylactic phenylephrine intravenous infusion is commenced (routine care). The infusion will be ceased immediately prior to transfer from the operating table to the participants bed in the operating theatre (prior to transfer to the post-anaesthesia recovery area). A study investigator will ensure that randomised participants receive the infusion. In the post-anaesthesia care unit blood samples will be taken to measure the intravenous concentration of the intervention (lignocaine)
Intervention code [1] 316649 0
Prevention
Intervention code [2] 316775 0
Treatment: Drugs
Comparator / control treatment
Intravenous 0.9% saline
Women allocated to the intravenous saline group (placebo group) will receive a bolus of 0.9% normal saline which has been calculated as though it were the active intervention (i.e. 1.0mg/kg of 1% lignocaine) over 15 minutes followed by a saline infusion calculated as per 1% lignocaine at 1.5 mg/kg/hour (based on their current day of surgery weight). This is to ensure the same volumes are used in both groups to maintain blinding. The bolus dose will commence immediately after the spinal anaesthetic injection at the same time as the prophylactic phenylephrine intravenous infusion is commenced (routine care). The infusion will be ceased immediately prior to transfer from the operating table to the participants bed in the operating theatre (prior to transfer to the post-anaesthesia recovery area).
Control group
Placebo

Outcomes
Primary outcome [1] 322649 0
The incidence (proportion (standard deviation and 95% confidence interval)) of chronic postsurgical pain (CPSP) at three months in women undergoing elective caesarean section surgery in the control/placebo group
Timepoint [1] 322649 0
Measured at 3 months after caesarean section surgery using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale
Primary outcome [2] 322779 0
The proportion of eligible participants who agree to be part of the study
Timepoint [2] 322779 0
At three months after study commencement study records will be reviewed to assess the proportion of eligible participants who agreed to being part of the study
Primary outcome [3] 322780 0
The number and proportion of participants who are followed-up at the three month review
Timepoint [3] 322780 0
Six months after study commencement study records will be reviewed to assess the number and proportion of participants who were followed-up at the three month review
Secondary outcome [1] 379177 0
Maternal plasma lignocaine concentration within one hour of cessation of intravenous infusion
Timepoint [1] 379177 0
Within one hour of cessation of intravenous infusion- Measured from a venous blood sample collected at that time and sent to specialist laboratory
Secondary outcome [2] 380096 0
Neonatal (umbilical vein and artery) plasma lignocaine concentration immediately after birth
Timepoint [2] 380096 0
Within 5 minutes of birth measured from a venous and arterial umbilical cord blood sample collected at that time and sent to specialist laboratory
Secondary outcome [3] 380097 0
The number of participants who adhere to the randomised controlled trial (RCT) protocol
Timepoint [3] 380097 0
Measured at 3 months are recruitment by examining study records documenting protocol adherence or non-adherence
Secondary outcome [4] 380098 0
The average time (in minutes) it takes to perform the follow-up consultation
Timepoint [4] 380098 0
Measured at the time of follow-up consultation using a timer activated at the start of the consultation and deactivated at the end of the consultation

Eligibility
Key inclusion criteria
Pregnant people. Age 18 years or greater, age 50 years or less; Gestational age 36 weeks; or greater Undergoing elective caesarean section surgery under neuraxial anaesthesia (spinal anaesthesia); Weight (on day of caesarean section surgery) 50 kg or greater, 120 kg or less
Minimum age
18 Years
Maximum age
50 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
American Society of Anesthesiology (ASA) class III, IV; Preoperative opioid therapy in the seven days prior to surgery; History of recreational drug use in the last 12 months prior to surgery; Allergies to local anaesthetics, morphine, fentanyl, paracetamol; Allergy or adverse reaction to non-steroidal anti-inflammatory drugs (NSAIDs); Body mass index (on day of caesarean section surgery) 45 kg/m¬2 or less.; Renal or liver impairment; Placental adhesive disorder defined on ultrasound and/or MRI; Known uterine fibroids.

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)
Group allocation will be placed in sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation with a computer-generated random number sequence will be used
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 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Two key aims are to determine the endpoint of baseline CPSP at three months and determine the safety of an intravenous lignocaine protocol. The first of these aims can be determined from the placebo group and the second can be determined from the intervention group. However, in order to answer feasibility questions, we need to conduct a RCT. We have therefore based the sample size calculation for this study on the endpoint of CPSP at three months. We have assumed that approximately 20% of the population will have CPSP at three months. The minimum sample size in the placebo group that would be expected to achieve the required accuracy (95% confidence interval within +/- 10% of the point estimate) is 61 women [SE(p) = v(p(100-p)/n)]. With a sample of 122 women safety data and the optimal bolus and infusion protocol can also be obtained. Therefore, the sample size for both the placebo and intervention groups is 61, To account for potential protocol deviations and sampling issues and participant dropouts we have increased the sample size to 65 women in each group ie. 130 women
We are also including another control group of 65 women undergoing emergency caesarean section surgery with epidural anaesthesia, and 65 women undergoing emergency caesarean section surgery with spinal anaesthesia to determine in that group the baseline CPSP incidence. These women will not be involved in the RCT but instead will be recruited in a prospective manner after their caesarean section. As there is no discrimination in the literature between women undergoing between elective or emergency caesarean-section surgery and CPSP rates we have made the same assumptions regarding the sample size as we made for the women undergoing elective caesarean section surgery. Study investigators will screen potential participants’ medical records to determine eligibility and then approach women after their caesarean section on the postnatal wards to discuss the study with them. The total sample size for the whole study is 260 women.

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)
VIC
Recruitment hospital [1] 15690 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 29110 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 304792 0
Hospital
Name [1] 304792 0
Royal Women's Hospital
Address [1] 304792 0
Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville, Victoria, Australia 3052
Country [1] 304792 0
Australia
Primary sponsor type
Hospital
Name
Royal Women's Hospital
Address
Locked Bag 300, corner Flemington Road and Grattan Street, Parkville, Victoria, Australia 3052
Country
Australia
Secondary sponsor category [1] 305111 0
None
Name [1] 305111 0
Address [1] 305111 0
Country [1] 305111 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305206 0
Royal Women's Hospital Human Research Ethics Committee EC00259
Ethics committee address [1] 305206 0
Locked Bag 300, Corner Flemington Road and Grattan Street, Parkville, Victoria, Australia 3052
Ethics committee country [1] 305206 0
Australia
Date submitted for ethics approval [1] 305206 0
28/10/2019
Approval date [1] 305206 0
17/01/2020
Ethics approval number [1] 305206 0
19_32

Summary
Brief summary
Chronic postsurgical pain (CPSP) after caesarean section surgery occurs in approximately one in five women. In Australia about one-third of women who give birth have caesarean section surgery. This means that in Australia over the next five years nearly 105,000 young women will be affected by CPSP. The impacts of this condition are significant with reduction in quality of life, reduced maternal-baby bonding, decreased mobility, and social isolation, and present an added burden for women facing the physical and emotional challenges of motherhood.

The problem of chronic pain also has other complications including the risk of dependence on morphine-based medications, poor mental health and loss of work productivity. Due to the far-reaching implications of chronic pain, there is an ongoing search for ways to prevent this. Data suggests that different types of anaesthesia and management around the time of surgery may minimise the risk of patients developing chronic pain following surgery.

A local anaesthetic drug, lignocaine, which has a long history of use and is safe in pregnancy and breastfeeding, has shown promising benefits in reducing chronic pain when it is given with an anaesthetic during other types of abdominal surgery. It has not been used in caesarean section surgery however we hope that it could be used in this surgery to reduce CPSP.

Before conducting a large study in this area, we need to collect information about the safety of lignocaine in women having caesarean section, information about whether a study is feasible on a large scale, and what the rate of CPSP is in women in contemporary Australia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99606 0
A/Prof Alicia Dennis
Address 99606 0
The Royal Women's Hospital, Locked Bag 300, Corner Flemington Road and Grattan Street, Parkville, Victoria, Australia 3052
Country 99606 0
Australia
Phone 99606 0
+61407685054
Fax 99606 0
Email 99606 0
alicia.dennis@thewomens.org.au
Contact person for public queries
Name 99607 0
Ms Liz Leeton
Address 99607 0
The Royal Women's Hospital, Locked Bag 300, Corner Flemington Road and Grattan Street, Parkville, Victoria, Australia 3052
Country 99607 0
Australia
Phone 99607 0
+61 38345 2000
Fax 99607 0
Email 99607 0
liz.Leeton@thewomens.org.au
Contact person for scientific queries
Name 99608 0
Ms Liz Leeton
Address 99608 0
The Royal Women's Hospital, Locked Bag 300, Corner Flemington Road and Grattan Street, Parkville, Victoria, Australia 3052
Country 99608 0
Australia
Phone 99608 0
+61 38345 2000
Fax 99608 0
Email 99608 0
liz.Leeton@thewomens.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results