Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000960550
Ethics application status
Approved
Date submitted
2/04/2024
Date registered
7/08/2024
Date last updated
7/08/2024
Date data sharing statement initially provided
7/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
ASAPP Pilot Trial: Efficacy of Azithromycin for Short cervix and Amniotic fluid sludge for the Prevention of Preterm birth
Scientific title
ASAPP: Efficacy of Azithromycin for Short cervix and Amniotic fluid sludge for the Prevention of Preterm birth, a pilot randomised controlled trial
Secondary ID [1] 311722 0
nil known
Universal Trial Number (UTN)
Trial acronym
ASAPP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preterm birth 333203 0
Short Cervical Length 333204 0
Intra-amniotic Infection 333205 0
Amniotic fluid sludge 333206 0
Pregnancy 333207 0
Vaginal dysbiosis 333208 0
Condition category
Condition code
Reproductive Health and Childbirth 329890 329890 0 0
Fetal medicine and complications of pregnancy
Reproductive Health and Childbirth 329891 329891 0 0
Complications of newborn
Reproductive Health and Childbirth 329892 329892 0 0
Antenatal care
Infection 329893 329893 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention in this pilot study is the use of oral Azithromycin tablets (6 x 250mg). Patients randomised to receive the investigational product will take two 250mg tablets on day one, followed by a 250mg tablet daily on days two-five. To monitor adherence to the intervention, participants will be asked to keep a medication diary and to bring their empty packaging or any unused tablets back to the research staff members.
Intervention code [1] 328187 0
Treatment: Drugs
Comparator / control treatment
The control treatment in this study is the use of placebo according to 1:1 randomisation. Patients randomised to receive placebo will take two 250mg placebo tablets on day one followed by a 250mg placebo tablet daily on days two-five. Pharmacologically inactive placebo tablets will be manufactured in accordance with any applicable GMP. The exact composition will be determined by the supplier.
Control group
Placebo

Outcomes
Primary outcome [1] 337660 0
The primary outcome for this pilot study is the presence of amniotic fluid sludge (AFS) visible on ultrasound, 2 weeks after the course of the treatment.
Timepoint [1] 337660 0
Two weeks post-randomisation.
Secondary outcome [1] 432733 0
Change in cervical length two weeks after randomisation and at 26+0 weeks’ gestation, relative to baseline.
Timepoint [1] 432733 0
Baseline, two weeks post-randomisation, 26+0 weeks’ gestation.
Secondary outcome [2] 432734 0
Change in high vaginal swab (HVS): microscopy or culture and sensitivity (this will be assessed as a composite outcome).
Timepoint [2] 432734 0
Baseline, two-weeks post-randomisation, 26 weeks’ gestation.
Secondary outcome [3] 432735 0
Maternal mortality.
Timepoint [3] 432735 0
Between time of randomisation and discharge from hospital following delivery.
Secondary outcome [4] 432736 0
Maternal infection.
Timepoint [4] 432736 0
Discharge from hospital following delivery.
Secondary outcome [5] 432737 0
Preterm premature rupture of membranes (PPROM).Rupture of membranes prior to the onset of labour before 37 completed weeks gestation.
Timepoint [5] 432737 0
Spontaneous premature rupture of membranes between randomisation and before onset of labour prior to 37 weeks gestation.
Secondary outcome [6] 432738 0
Pre labour rupture of membranes (PROM)
Timepoint [6] 432738 0
Prelabour rupture of membranes prior to the onset of labour at term (after 37 completed weeks gestation).
Secondary outcome [7] 432739 0
Maternal adverse effects from azithromycin.
Timepoint [7] 432739 0
Two weeks after randomisation.
Secondary outcome [8] 432740 0
Gestational age at birth.
Timepoint [8] 432740 0
At birth.
Secondary outcome [9] 433182 0
Birth weight.
Timepoint [9] 433182 0
At birth.
Secondary outcome [10] 433183 0
Perinatal mortality.
Timepoint [10] 433183 0
Fetal death at any stage following randomisation and prior to birth. Neonatal death up to 28 days following birth.
Secondary outcome [11] 433184 0
Early neurodevelopmental morbidity.
Timepoint [11] 433184 0
Up until hospital discharge following birth.
Secondary outcome [12] 433185 0
Gastrointestinal morbidity due to necrotising enterocolitis.
Timepoint [12] 433185 0
Up until hospital discharge following birth.
Secondary outcome [13] 433186 0
Infection.
Timepoint [13] 433186 0
Up until hospital discharge following birth.
Secondary outcome [14] 433187 0
Respiratory morbidity.
Timepoint [14] 433187 0
Up until hospital discharge following birth.
Secondary outcome [15] 433492 0
Feasibility.
Timepoint [15] 433492 0
Proportion of eligible patients who consent to randomisation will be assessed at the time of randomisation.
the proportion of consented participants who complete all trial procedures will be assessed at the conclusion of study.
Secondary outcome [16] 434048 0
Change in maternal microbiome composition.
Timepoint [16] 434048 0
Baseline, two-weeks post-randomisation, 26 weeks’ gestation.

Eligibility
Key inclusion criteria
Pregnant women from 13 weeks 0 days gestation to 24 weeks 0 days gestation, with cervical length less than or equal to 25.0mm, sonographic appearance of amniotic fluid sludge and absence of symptoms suggestive of labour at randomisation.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Multiple gestation, major or lethal fetal congenital abnormality, placenta praevia/vasa praevia, PPROM, clinical signs suggestive of chorioamnionitis, indicated preterm delivery at time of randomisation, known allergy to Azithromycin, use of medications likely to prolong QT interval, history of cardiac disease, known hepatic impairment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be performed centrally via web based randomisation. Participants will be allocated a numbered container containing the investigational product. All containers will look identical apart from the container number which will correspond to the concealed randomisation sequence. The active and placebo medications inside the bottle will appear identical.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified 1:1 randomisation with computerised sequence generation.
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 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All outcomes will be compared between the intervention and control groups using an intention-to-treat analysis. The proportion of women with sonographic appearances of AFS in both the treatment and control groups will be compared at 2 weeks following randomisation (primary endpoint) and at 26+0 weeks’ gestation (secondary endpoint) using the Chi squared statistic, as this represents categorical data. The mean cervical length in both the treatment and control groups will be compared at 2 weeks following randomisation and at 26+0 weeks’ gestation using the Mann-Whitney U test (assuming the cervical lengths will not be normally distributed), as this represents metric data.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2024
Actual
Date of last participant enrolment
Anticipated
1/07/2027
Actual
Date of last data collection
Anticipated
1/02/2028
Actual
Sample size
Target
84
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26302 0
Joan Kirner Women’s and Children’s Hospital - St Albans
Recruitment hospital [2] 26303 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 26304 0
The Royal Women's Hospital - Parkville
Recruitment hospital [4] 26305 0
Eastern Health - Box Hill
Recruitment postcode(s) [1] 42274 0
3021 - St Albans
Recruitment postcode(s) [2] 42275 0
3168 - Clayton
Recruitment postcode(s) [3] 42276 0
3052 - Parkville
Recruitment postcode(s) [4] 42277 0
3128 - Box Hill

Funding & Sponsors
Funding source category [1] 316052 0
Government body
Name [1] 316052 0
Department of Jobs, Skills, Industry and Regions - Victorian Medical Research Acceleration Fund
Country [1] 316052 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 318311 0
None
Name [1] 318311 0
Address [1] 318311 0
Country [1] 318311 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314872 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 314872 0
Ethics committee country [1] 314872 0
Australia
Date submitted for ethics approval [1] 314872 0
13/12/2023
Approval date [1] 314872 0
20/12/2023
Ethics approval number [1] 314872 0
HREC/92838/MH-2023-405816(v2)

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

Contacts
Principal investigator
Name 133006 0
Prof Joanne Said
Address 133006 0
Sunshine Hospital, 176 Furlong Rd, St Albans, Victoria 3021
Country 133006 0
Australia
Phone 133006 0
+61 411 460 940
Fax 133006 0
Email 133006 0
[email protected]
Contact person for public queries
Name 133007 0
Joanne Said
Address 133007 0
Sunshine Hospital, 176 Furlong Rd, St Albans, Victoria 3021
Country 133007 0
Australia
Phone 133007 0
+61 3 9055 2400
Fax 133007 0
Email 133007 0
[email protected]
Contact person for scientific queries
Name 133008 0
Joanne Said
Address 133008 0
Sunshine Hospital, 176 Furlong Rd, St Albans, Victoria 3021
Country 133008 0
Australia
Phone 133008 0
+61 3 9055 2400
Fax 133008 0
Email 133008 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual, deidentified participant data underlying published results will be available.
When will data be available (start and end dates)?
Beginning 12 months after publication up until 5 years after publication.
Available to whom?
Researchers who provide a methodologically sound proposal at the discretion of the Principal Investigator and Sponsor.
Available for what types of analyses?
IPD Meta-analyses.
How or where can data be obtained?
By request to the Principal Investigator (email [email protected]).


What supporting documents are/will be available?




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.