The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616000398404
Ethics application status
Approved
Date submitted
13/01/2016
Date registered
29/03/2016
Date last updated
29/03/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Low dose versus standard dose oxytocin in pregnant women undergoing elective caesarean delivery
Scientific title
Effect of 3 units versus 5 units slow intravenous bolus oxytocin on postpartum blood loss in women undergoing elective caesarean delivery
Secondary ID [1] 288307 0
Nil known.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstetric anaesthesia for elective caesarean section 297269 0
Condition category
Condition code
Anaesthesiology 297505 297505 0 0
Anaesthetics
Reproductive Health and Childbirth 297506 297506 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Slow bolus intravenous injection of 3 units oxytocin administered by anaesthetist over 60 seconds at the time of delivery.
Intervention code [1] 293603 0
Prevention
Comparator / control treatment
Slow bolus intravenous injection of 5 units oxytocin administered by anaesthetist over 60 seconds at the time of delivery.
Control group
Dose comparison

Outcomes
Primary outcome [1] 297035 0
Twenty four hour postpartum blood loss (presented as a continuous variable) utilising a gravimetric measurement technique.
Timepoint [1] 297035 0
Cumulative total over 24 hours after delivery
Secondary outcome [1] 319891 0
Uterine tone assessed as adequate or inadequate by an obstetrician
Timepoint [1] 319891 0
3 minutes after oxytocin administration.
Secondary outcome [2] 319892 0
Need for additional uterotonic agents as requested by obstetrician in response to inadequate uterine tone.
Timepoint [2] 319892 0
First 30 minutes after oxytocin administration.
Secondary outcome [3] 319893 0
Cumulative phenylephrine dose is documented by research nurse on case report form.
Timepoint [3] 319893 0
First 30 minutes after oxytocin administration.
Secondary outcome [4] 319894 0
Vomiting (defined as the ejection of stomach content)
Timepoint [4] 319894 0
First 30 minutes after oxytocin administration.
Secondary outcome [5] 319895 0
Hypotension defined as a mean arterial pressure (MAP) less than 65 mmHg using non-invasive blood pressure monitoring.
Timepoint [5] 319895 0
First 10 minutes after oxytocin administration

Eligibility
Key inclusion criteria
ASA I –II, term pregnancy (>38 weeks), aged 18 to 40 years and scheduled for elective caesarean delivery.
Minimum age
18 Years
Maximum age
40 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Clinical history of hypertensive disorders (pre eclampsia; chronic hypertension), haemodynamic instability (systolic blood pressure < 100 mmHg), bleeding diastasis (thrombocytopenia, coagulopathies) and history of uterine atony causing post-partum haemorrhage.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Nil
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Decision regarding treatment allocation was left to the treating anaesthesiologist who were instructed not to select the dose based on specific patient characteristics.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size calculations were based on blood loss data from Sheehan et al (mean +/- SD, 843 +/-487 ml) and an inferiority margin of 300 ml deemed as clinically significant. With beta = 0.20 and alpha = 0.05, 33 patients were required for each group to ensure that the upper limit of a one-sided 95% confidence interval would be below the non-inferiority limit of 300ml.

Descriptive statistics of the study groups at baseline; means and standard deviations or 95 % confidence intervals (95% CI) will be presented except where indicated. Geometric means and standard error of the mean (SEM) will be presented for skewed outcomes. Group differences will be assessed using the two sample equal-variance t-test and chi-squared or Fisher exact tests where required.
The primary outcome will be regressed on oxytocin dose (3IU vs 5IU) adjusted for BMI, pre-delivery vasopressor dose, parity and the presence of a uterine atony risk factor. A logarithmic transformation of the outcome variable will be performed after assessment of model residuals, back-transformed (geometric) means and 95% confidence intervals will be presented, and these limits will be used to assess non-inferiority.
Propensity weighting will be used in all regression models to adjust for the non-random allocation of participants to treatment groups. A logistic regression model with the covariates; age, weight, previous caesarean section, seniority of obstetrician, seniority of anaesthetist, will be used to generate propensity weights.
All models will be checked for violation of model assumptions. A p-value of 0.05 will be considered significant.

Recruitment
Recruitment status
Completed
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)
TAS
Recruitment hospital [1] 5031 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 12518 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 292682 0
Charities/Societies/Foundations
Name [1] 292682 0
High Blood Pressure Research Council of Australia
Address [1] 292682 0
4, 184 Main St, Lilydale, VIC, 3140
Country [1] 292682 0
Australia
Primary sponsor type
Hospital
Name
Royal Hobart Hospital
Address
48 Liverpool Street, Hobart, Tasmania, 7000
Country
Australia
Secondary sponsor category [1] 291402 0
None
Name [1] 291402 0
NA
Address [1] 291402 0
NA
Country [1] 291402 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294151 0
Tasmania Health & Medical Human Research Ethics Committee (EC00337)
Ethics committee address [1] 294151 0
301 Sandy Bay Road, Sandy Bay,Hobart, TAS, 7001
Ethics committee country [1] 294151 0
Australia
Date submitted for ethics approval [1] 294151 0
28/02/2011
Approval date [1] 294151 0
30/05/2011
Ethics approval number [1] 294151 0
H11695

Summary
Brief summary
This study sought to determine whether 3IU oxytocin was comparable to standard 5IU regarding postpartum blood loss in pregnant women undergoing elective caesarean delivery under spinal anaesthetic, but could reduce blood pressure elevating medication (vasopressor) requirements and adverse events. We hypothesized that patients receiving 3IU oxytocin would be non-inferior to 5IU regarding postpartum blood loss and superior regarding uterine tone, incidence of low blood pressure (hypotension), blood pressure elevating medication (vasopressor) requirements and adverse events.
Trial website
Trial related presentations / publications
The study was presented at the 2015 Australian and New Zealand College of Anaesthetists (ANZCA) and Faculty of Pain Medicine (FPM) Annual Scientific Meeting (ASM) Adelaide, May 2 - 5, 2015.
Public notes

Contacts
Principal investigator
Name 62714 0
Dr Nico Terblanche
Address 62714 0
Department of Anaesthesia and Perioperative Medicine, Royal Hobart Hospital
48 Liverpool St, Hobart, 7001, Tasmania, Australia
Country 62714 0
Australia
Phone 62714 0
+61 3 62227866
Fax 62714 0
Email 62714 0
nico.terblanche@ths.tas.gov.au
Contact person for public queries
Name 62715 0
Dr Nico Terblanche
Address 62715 0
Department of Anaesthesia and Perioperative Medicine, Royal Hobart Hospital
48 Liverpool St, Hobart, 7001, Tasmania, Australia
Country 62715 0
Australia
Phone 62715 0
+61 3 62227866
Fax 62715 0
Email 62715 0
nico.terblanche@ths.tas.gov.au
Contact person for scientific queries
Name 62716 0
Dr Nico Terblanche
Address 62716 0
Department of Anaesthesia and Perioperative Medicine, Royal Hobart Hospital
48 Liverpool St, Hobart, 7001, Tasmania, Australia
Country 62716 0
Australia
Phone 62716 0
+61 3 62227866
Fax 62716 0
Email 62716 0
nico.terblanche@ths.tas.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary