None listed
Conditions
Brief summary
Preterm birth (PTB) is a major problem of global importance. Although it has been known for some time that PTBs at the very early gestational ages are often associated with intrauterine inflammation and infection, clinical strategies to treat the infection have largely been unsuccessful. This study aims to undertake a prospective, open-label, randomised clinical trial of a ‘screen and treat’ program aimed at preventing infection-driven spontaneous PTB (sPTB). The design is built upon an earlier European trial which achieved a 40% overall reduction in sPTB rate, and we have added improved efficacy in risk-identification and treatment strategies. The single centre, multi-site study will recruit women with singleton pregnancies, asymptomatic for vaginal infection, attending antenatal clinics at 14-20 weeks’ gestation in two public hospitals within the Perth metropolitan area. A total of 6174 women will be recruited over a 2 year period, randomised after recruitment to either a control or intervention group (n=3087/group). Participants will self-collect a vaginal swab to be screened for microbial risk factors using a unique DNA-based assay. Participants in the control group will receive normal care and results of the tests will not available until after the pregnancy is completed. Intervention group participants will be informed of their result and mailed their antimicrobial therapy plus a vaginal probiotic to reduce relapse rates; re-screening will occur at 22-28 weeks’ to assess treatment efficacy. The primary endpoint is reduction in sPTB <37 weeks’ gestation; secondary endpoints included additional delivery outcomes, maternal morbidities and neonatal mortality and morbidities. The trial is conservatively powered to detect a 30% reduction in overall sPTB rate from 4.83 to 3.38% (80% power, alpha=0.05). If this success were to be translated nationally, the reduction in number of PTBs each year would be approximately 4500 cases.
Interventions
Asymptomatic pregnant women will have a self-collected vaginal swab screened using our GLU microbial DNA assay (patent pending). Women who screen GLU+ve will receive oral azithromycin (250 mg for 7 days) and vaginal clindamycin cream (2%) for 7 days. Immediately following antimicrobial treatment, women will commence vaginal probiotic therapy with Canesflor (Bayer). Treatment consists of one vaginal capsule each night for six consecutive days, followed by one capsule per week for four weeks.
GLU
Asymptomatic pregnant women will have a self-collected vaginal swab screened using our GLU microbial DNA assay (patent pending). Women who screen GLU+ve will receive oral azithromycin (250 mg for 7 days) and vaginal clindamycin cream (2%) for 7 days. Immediately following antimicrobial treatment, women will commence vaginal probiotic therapy with Canesflor (Bayer). Treatment consists of one vaginal capsule each night for six consecutive days, followed by one capsule per week for four weeks. GLU +ve participants in the intervention group will be contacted by phone by study research midwives a few days after the medications are mailed out to ensure participants have obtained their prescription and check comprehension and compliance. Women in the intervention group will be asked to take another three vaginal swabs (two COPAN E-swabs and one COPAN UTM swab) at 22-28 weeks (after completion of the 5-week probiotic course) and mail them on the day of collection using a pre-addressed express post envelope to the lab for re-testing. One of the E-swabs will be analysed to evaluate treatment efficacy and the additional swabs will be frozen at -80 degrees C and evaluated by culture should GLU test analysis indicate treatment failure. The purpose of culture analysis will be to isolate the target organisms and ascertain antibiotic MIC values. Follow-up testing will not be conducted until the recruitment and delivery phase of the trial is complete, hence the results will not be provided to the women and will be of no relevance to their obstetric care as they will have already given birth to their child. A questionnaire on medication compliance and feedback will also be returned at the time of follow-up swab collection. GLU -ve women will not receive any antimicrobial treatment and will continue to receive standard of care for the remainder of their pregnancy, same as in the control group.
Sponsors
University of Western Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Prevention
Masking
Blinded (masking used) (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
16 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Singleton pregnancy and ultrasound-confirmed gestation.
Exclusion criteria
Multiple pregnancies, symptomatic vaginal infections, vaginal bleeding, rupture of membranes, active contractions, antimicrobial therapy within 14 days prior to recruitment.
Outcome results
None listed