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Clinical Study of STI Screening to Prevent Adverse Birth and New-born Outcomes

Not Applicable
Completed
Conditions
Birth Outcomes
HIV/AIDS
Vaginal Microbiome
Trichomonas Vaginalis
Pregnancy
Sexually Transmitted Infection
Cost-effectiveness
Chlamydia Trachomatis
Neisseria Gonorrhoeae
Antenatal Care
Interventions
Diagnostic Test: First antenatal care + test-of-cure
Diagnostic Test: First antenatal care + week 30-34 gestation (no test-of-cure)
Registration Number
NCT04446611
Lead Sponsor
Foundation for Professional Development (Pty) Ltd
Brief Summary

This study aims to evaluate different screening strategies to decrease the burden of Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV) among pregnant women, and reduce adverse birth outcomes. In turn it aims to evaluate the cost per pregnant woman screened and treated, cost of adverse birth outcomes, and cost-effectiveness per sexually transmitted infection (STI) and disability-adjusted life-year (DALY) averted. Furthermore, this study will incorporate a vaginal microbiome sub-study aimed to investigate the relationship between the vaginal microbiome and persistent Chlamydial infections in pregnant women.

Aim 1 and 2: The intervention includes diagnostic testing at a woman's first antenatal care visit using the Xpert® platform with same-day treatment for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis infection with either a test-of-cure three weeks post-treatment (arm 1) or a repeat test at 30-34 weeks gestation (arm 2) compared to the standard of care, i.e. syndromic management (arm 3).

Aim 3: Case-control study to investigate role vaginal microbiome in STI treatment outcomes

Detailed Description

Prevalence of STIs is high among pregnant women in South Africa and most infections remain untreated. Untreated infections impact on pregnancy and birth outcomes. Good diagnostic and point-of-care (POC) tests are available, such as the GeneXpert platform. The health impact, cost-effectiveness and approaches to optimization of STI diagnostic screening during pregnancy are unknown.

In order to 1) identify optimal, cost-effective screening strategies that decrease the burden of STIs during pregnancy and reduce adverse birth outcomes, 2) informs evidence to WHO's guidelines to introduce aetiologic STI screening globally and 3) elucidate the role of the vaginal microbiome in STI treatment outcomes, the investigators propose three Specific Aims:

1. Evaluate different screening strategies to decrease the burden of Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis among pregnant women and reduce adverse birth outcomes

2. Evaluate cost per pregnant woman screened and treated, cost of adverse birth outcomes, and cost-effectiveness per STI and disability-adjusted life-year (DALY) averted

3. Investigate the relationship between the vaginal microbiome and persistent Chlamydial infections in pregnant women

STI screening and treatment for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis will be offered to HIV-infected and non-infected women (age \>18 years) whom present for first antenatal care services. An effectiveness-implementation hybrid type 1 three-arm (1:1:1) randomized controlled trial (RCT), will be employed to evaluate different screening strategies to decrease the burden of Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis among pregnant women, and reduce adverse birth outcomes.

The costs of the different STI screening strategies relative to control will be estimated based on literature review and performance/implementation characteristics and compared, in addition to the costs of managing adverse birth outcomes. Decision analytic modelling will estimate the cost-effectiveness per STI, and DALY averted (Aim 2).

Depending on the randomization arm, participants will be scheduled to be seen various times throughout pregnancy by the study team; antenatal care visits will be conducted in line with national policy. All post-partum mothers and infants will be asked to be seen at the first post-delivery clinic visit.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
2247
Inclusion Criteria

Not provided

Exclusion Criteria
  1. Planning to relocate during pregnancy or deliver in an MOU outside of BCM
  2. Unknown HIV status (e.g. refusal, invalid test result)
  3. Currently participating in another ANC/HIV study
  4. When the ultrasound confirms ≥20 weeks gestation at first ANC

Inclusion criteria for Neonates:

  1. born to mothers that provided informed consent to participate in study, 2) provision of updated verbal consent by mother to collect and test specimens for STIs

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Test at 1st ANC + Test-of-Cure (Treatment 1)First antenatal care + test-of-cureSingle point-in-time diagnostic screening plus test-of-cure three weeks post-treatment
Test at 1st ANC + 30-34 gestation (Treatment 2)First antenatal care + week 30-34 gestation (no test-of-cure)Repeated diagnostic screening at first antenatal care and 30-34 weeks gestation
Primary Outcome Measures
NameTimeMethod
Frequency of adverse birth outcomes among study armsRecorded within 2 weeks of delivery

Adverse birth outcomes as defined by a composite measure of preterm birth (born alive before 370/7 weeks gestation) or low birth weight (less than 2500g) as recorded in the maternity case records

Secondary Outcome Measures
NameTimeMethod
Incidence of Preterm birth among study armsAt delivery

The frequency of live births before 37 weeks' gestation, as validated by ultrasound dating at first antenatal visit

Incidence of STI in infants exposed to infection in their mothersSTI testing in mother and infants within 2 weeks post-delivery to a maximum of 6 weeks post-delivery

Frequency of Chlamydia, Gonorrhoeae, and/or Trichomonas infection among infants born to a mother in whom infection is detected post-delivery

Change in STI prevalence (a) between baseline visit and delivery within the experimental arms and (b) between the experimental and control arms by delivery.Between baseline (first antenatal visit <27 weeks' gestation) and delivery outcome (collected within 2 weeks post-delivery)

To calculate the relative and absolute change in Chlamydia, Gonorrhea, and Trichomoniasis prevalence. Additionally, generalized estimating equations to test for variation in STI prevalence among study arms will be done, adjusting for potential effect modifiers and confounding variables

Correlation between Bacterial vaginosis-associated vaginal community state types and clearance of Chlamydia infectionAssessed through study completion

To determine the correlation between Bacterial vaginosis-associated vaginal community state types and chlamydial infection clearance as measured by a positive or negative chlamydial test result no less than three weeks after treatment and thence weekly until a negative Chlamydia test result is recorded.

Frequency of fetal loss (miscarriage or stillbirth) among study armsAssessed through study completion

Composite frequency of miscarriage (\<28 weeks' gestation) or stillbirth (\> 28 weeks' gestation) and the individual components, as indicated in the maternal case records

Incidence of Low birthweight infants among study armsWithin 2 weeks post-delivery

The frequency of live births with birth weight \< 2500g, as recorded in the maternity case records

Trial Locations

Locations (1)

Buffalo City Metro

🇿🇦

East London, Eastern Cape, South Africa

Buffalo City Metro
🇿🇦East London, Eastern Cape, South Africa
Andrew Medina-Marino, PhD, MPH
Principal Investigator
Jeffrey Klausner, MD, MPH
Principal Investigator
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