Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001705178
Ethics application status
Approved
Date submitted
26/11/2019
Date registered
4/12/2019
Date last updated
16/01/2024
Date data sharing statement initially provided
4/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Cefazolin v Placebo for pre-incision prophylaxis in very low-risk women undergoing elective caesarean section: A Feasibility Study.
Scientific title
Intravenous Cefazolin v Placebo for pre-incision prophylaxis in very low-risk women undergoing elective caesarean section: RCT Pilot Feasibility Study.
Secondary ID [1] 299915 0
None
Universal Trial Number (UTN)
U1111-1244-5557
Trial acronym
ASCENT (Allergic Symptoms after CaesarEaN SecTion) Trial
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Immune system 315341 0
Wound infection post caesarean section 315342 0
Atopic disease in infancy 315419 0
Condition category
Condition code
Inflammatory and Immune System 313641 313641 0 0
Allergies
Infection 313642 313642 0 0
Other infectious diseases
Reproductive Health and Childbirth 313715 313715 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single intravenous pre-operative dose. 2 grams of cefazolin will be prepared in 100 mL of normal saline, with opaque labelling such that the contents of the bag cannot be visualized, exactly the same as the placebo. After administration over 1-2 minutes, it will be “flushed through” with a second 100 ml bag of labelled normal saline 0.9%.
The intervention will be administered within 30 minutes of skin incision.
Nurse notes will document preparation (unblinded nurse)
Intervention code [1] 316188 0
Prevention
Comparator / control treatment
Single intravenous pre-operative dose. 100 ml of 0.9% (normal) saline (Placebo) will be prepared with opaque labelling such that the contents of the bag cannot be visualized. After administration over 1-2 minutes, it will be “flushed through” with a second 100 ml bag of labelled normal saline 0.9%.

The placebo will be administered within 30 minutes of skin incision.
Nurse notes will document preparation (unblinded nurse)
Control group
Placebo

Outcomes
Primary outcome [1] 322079 0
Incidence of infant allergic disease, composite outcome, (atopic dermatitis, food allergy and recurrent wheeze) assessed by parental questionnaire.

Presence of atopic dermatitis will be identified according to the definitions of the UK Working Party or the presence of parent-report of doctor-diagnosed atopic dermatitis/eczema during the first 12 months of life

Presence of food allergy will be defined as parent-report of doctor-diagnosed food allergy in the first 12 months of life

Presence of recurrent wheeze will be defined as greater than or equal to 3 episodes of wheeze in the first 12 months of life
Timepoint [1] 322079 0
Assessed when the infant is 12 months of age.
Secondary outcome [1] 377247 0
Rate of recruitment – assessed as number of women approached and number accepted, over the time-course of recruitment. This will include rate of obtaining consent and also proportion of exclusions/drop-outs for other reasons (for example: consent obtained, but delivered early by emergency caesarean section).

Number of women approached, number consented, number commencing study, over the period of time
Timepoint [1] 377247 0
At recruitment
Secondary outcome [2] 377248 0
Reasons for non-participation - assessed by verbal report from participant at time of recruitment
Timepoint [2] 377248 0
Assessed at time of recruitment
Secondary outcome [3] 377249 0
Ability to standardize operating room processes for all patients.
A process checklist will be used: elements to be standardised:
• Skin preparation with alcoholic chlorhexidine solution
• Pre-incision antibiotic/placebo
• Uterine incision – lower segment uterine incisions only
• Spontaneous separation of placenta
• Wound closure (sutures not staples)
• No wound drain
• Wound dressing:
Timepoint [3] 377249 0
Assessed on Day 1 by observation.
Secondary outcome [4] 377250 0
Participant experience assessed by 5-point Likert scales.
Timepoint [4] 377250 0
Day 30 (Day 1 is day of surgery)
Secondary outcome [5] 377252 0
Practicality and adequacy of randomizing and blinding procedures. Assessed using clinician survey.
Bang's and James' Blinding Indices will be used. These are previously validated surveys.
Timepoint [5] 377252 0
The treating anaesthetist will be surveyed at the time of administration, Day 1. The treating obstetrician will be surveyed on Day 2.
Secondary outcome [6] 377253 0
Accessibility to required maternal clinical outcome data from clinical database
Timepoint [6] 377253 0
Day 1-30 Day 1 is day of surgery
Assessed daily from Day 1 to discharge
Assessed weekly from discharge until Day 30
Secondary outcome [7] 377254 0
Maternal blood sampling (10 mLs each) obtained prior to administration of the study drug (taken from the intravenous cannula) and after closure of the wound.Exploratory outcome: Inflammatory markers
Timepoint [7] 377254 0
Day 1 (Day 1 is day of surgery)
Secondary outcome [8] 377255 0
Maternal vaginal swabs for microbiological analysis obtained before and after administration of study drug, exploratory outcome.
Timepoint [8] 377255 0
Day 1 (Day 1 is Day of surgery)
Secondary outcome [9] 377256 0
Amniotic fluid sample obtained for exploratory analysis of immunomodulatory proteins.
Timepoint [9] 377256 0
Day 1 (Day 1 is Day of surgery)
Secondary outcome [10] 377258 0
Infant faecal samples for exploratory microbiology assessments
Timepoint [10] 377258 0
Day 90 (Day 1 is day of surgery)
Secondary outcome [11] 377259 0
Maternal breast milk for exploratory immunological analysis
Timepoint [11] 377259 0
Day 14, 30, 60 (Day 1 is day of surgery)
Secondary outcome [12] 377260 0
Infectious complications outcomes based on CDC definitions of surgical site infection. Assessed by clinician examination and diagnosis using CDC checklist.
Timepoint [12] 377260 0
Day 1-30 (Day 1 is Day of surgery)
Secondary outcome [13] 377261 0
PROMIS Global 10 Health Scale – Short Form 10a
Timepoint [13] 377261 0
Day 8, 21, 14, 90 (Day 1 is day of surgery)
Secondary outcome [14] 377450 0
Infant faecal samples for exploratory immunology assessments
Timepoint [14] 377450 0
Day 90 (Day 1 is Day of surgery)
Secondary outcome [15] 377451 0
Accessibility to neonatal outcome data, from database
Timepoint [15] 377451 0
Day 1-3-, day 1 is day of surgery
Secondary outcome [16] 394268 0
Allergic disease composite end-point:

Presence of atopic dermatitis will be identified according to the definitions of the UK Working Party21 or the presence of parent-report of doctor-diagnosed atopic dermatitis/eczema during the first 12 months of life

Presence of food allergy will be defined as parent-report of doctor-diagnosed food allergy in the first 12 months of life

Presence of recurrent wheeze will be defined as greater than or equal to 3 episodes of wheeze in the first 12 months of life
Timepoint [16] 394268 0
12 months following the day of surgery
Secondary outcome [17] 394269 0
Patient experience survey via email

Assessed by an adaptation of a previously validated research participant experience survey tool. Participant self-reports on a series of statements answered using 5-point Likert scales. Adapted to include “Medical-technical aspects”, “Interpersonal aspects”, “Organizational aspects” and “Follow up communication”.
Timepoint [17] 394269 0
Day 360 (Day 1 is day of surgery)

Eligibility
Key inclusion criteria
Scheduled for elective caesarean section. Age < 40 years and greater than or equal to 18 years, gestation greater than 37 weeks, membranes intact, body mass index less than 25, not in labour, non-smoking, haemoglobin greater than 110g/L, non-diabetic, (Type 1, Type 2 or gestational diabetes) American Society of Anesthesiologists score (ASA score) = 2. (The ASA score is classification of physical status: 1 being a healthy patient, 5 being a moribund patient and 6 being an organ donor. Pregnancy is classified as a minimum score of 2.)
Minimum age
18 Years
Maximum age
39 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Allergy to cephalosporin antibiotics, allergy to chlorhexidine, conditions pre-disposing to haemorrhage (anticoagulation, thrombocytopaenia, abnormal placentation) conditions pre-disposing to infection (immunosuppression, autoimmune disorders, steroid use), complex cardiac or respiratory disease, classical uterine incision (vertical), use of a wound drain, manual removal of placenta.

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)
Allocation concealment will be by central randomization
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
REDCAP randomization facility
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
Safety/efficacy
Statistical methods / analysis
As a pilot study, it will not be powered to analyze the difference in incidence between the two groups. Undertaking this pilot study allows us to assess the feasibility of undertaking the study on a larger scale. The primary analysis will be a comparison of the incidence rate of the composite primary outcome between the treatment and placebo group using a likelihood ratio test. Each of the individual components will also be analysed separately. The results will be used to determine the sample size required to power the future clinical trial. Conducting the pilot study for 6 months should be sufficiently long to implement the protocol and highlight any issues in the logistics of running the trial, and to evaluate the recruitment, blinding and data collection procedures. The progress of the trial will be continually monitored by the trial team and approximately half-way through the enrolment the team will meet to review issues and potentially implement changes that can be evaluated in the second half of the trial. In terms of infection risk, at this time the investigator team and the Data Safety Monitoring Board will review the number and severity of infections and decide whether or not to proceed.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Other reasons/comments
Other reasons
Recruitment ceased after 30 patients randomised. Proved non-feasible. However adequate biological samples were obtained to provide robust statistical comparisons of microbiome.
Date of first participant enrolment
Anticipated
31/05/2021
Actual
12/08/2021
Date of last participant enrolment
Anticipated
3/04/2023
Actual
22/06/2023
Date of last data collection
Anticipated
29/12/2023
Actual
Sample size
Target
50
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 15337 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 28647 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 304375 0
Hospital
Name [1] 304375 0
Royal Brisbane and Women's Hospital
Country [1] 304375 0
Australia
Funding source category [2] 315598 0
Commercial sector/Industry
Name [2] 315598 0
Ferring Pharmaceuticals
Country [2] 315598 0
Australia
Funding source category [3] 315599 0
Hospital
Name [3] 315599 0
Metro North Health
Country [3] 315599 0
Australia
Funding source category [4] 315600 0
Charities/Societies/Foundations
Name [4] 315600 0
Children's Hospital Foundation
Country [4] 315600 0
Australia
Primary sponsor type
Hospital
Name
Royal Brisbane and Women's Hospital
Address
Butterfield St
Herston 4006
QLD
Australia
Country
Australia
Secondary sponsor category [1] 304628 0
None
Name [1] 304628 0
Address [1] 304628 0
Country [1] 304628 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304814 0
Royal Brisbane and Women's Hospital
Ethics committee address [1] 304814 0
Ethics committee country [1] 304814 0
Australia
Date submitted for ethics approval [1] 304814 0
28/01/2020
Approval date [1] 304814 0
09/03/2020
Ethics approval number [1] 304814 0
HREC/2020/QRBW/58840

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98294 0
A/Prof Victoria Eley
Address 98294 0
RBWH
Butterfield St
Herston 4006
QLD
Country 98294 0
Australia
Phone 98294 0
+61 438127616
Fax 98294 0
Email 98294 0
[email protected]
Contact person for public queries
Name 98295 0
Victoria Eley
Address 98295 0
RBWH
Butterfield St
Herston 4006
QLD
Country 98295 0
Australia
Phone 98295 0
+61 438127616
Fax 98295 0
Email 98295 0
[email protected]
Contact person for scientific queries
Name 98296 0
Victoria Eley
Address 98296 0
RBWH
Butterfield St
Herston 4006
QLD
Country 98296 0
Australia
Phone 98296 0
+61 438127616
Fax 98296 0
Email 98296 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethical approval was not obtained to cover this disclosure.


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.