Clinical trial NCT04446611: Clinical Study of STI Screening to Prevent Adverse Birth and New-born Outcomes
Official title: Clinical Study of STI Screening to Prevent Adverse Birth and New-born Outcomes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sexually Transmitted Infection
HIV/AIDS
Cost-effectiveness
Birth Outcomes
Vaginal Microbiome
Neisseria Gonorrhoeae
Chlamydia Trachomatis
Trichomonas Vaginalis
Antenatal Care
Pregnancy
Keywords: Sexually transmitted infection
Neisseria gonorrhoeae
Chlamydia trachomatis
Trichomonas vaginalis
Antenatal care
HIV/AIDS
Birth outcomes
South Africa
Vaginal microbiome
Pregnancy
Diagnostic testing
Lead sponsor: Foundation for Professional Development (Pty) Ltd
Sponsor class: OTHER
Collaborators: name: University of Southern California
name: National Institutes of Health (NIH)
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: University of Cape Town
name: University of Alabama at Birmingham
name: Louisiana State University Health Sciences Center in New Orleans
First posted: 2020-06-25
Enrollment: 2247
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The intervention will incorporate diagnostic testing using the Xpert® platform with same-day treatment for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis infection at first ANC (aim 1 and 2) with either a test-of-cure (arm 1) or 30 weeks repeat testing as follow-up (arm 2) compared to the standard of care (arm 3), i.e. syndromic management as per the South African guidelines. It is thus a 3-arm (1:1:1) control trial with additional components of vaginal microbiome analysis, economic evaluation and qualitative insights.
Primary purpose: SCREENING

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.

Eligibility criteria: Inclusion Criteria for pregnant women:

1. Age≥18 years
2. Currently pregnant based on positive urine pregnancy test
3. Attending first ANC visit for current pregnancy
4. Gestational age \<20 weeks
5. Agreeing to nurse-collected specimens
6. Resident in Buffalo City Municipality (BCM)
7. Intent to deliver in one of the four midwife obstetric units (MOUs) in BCM

Gestational age will be confirmed via ultrasound

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

Primary outcomes:
measure: Frequency of adverse birth outcomes among study arms
timeFrame: Recorded within 2 weeks of delivery
Secondary outcomes:
measure: Change in STI prevalence (a) between baseline visit and delivery within the experimental arms and (b) between the experimental and control arms by delivery.
timeFrame: Between baseline (first antenatal visit <27 weeks' gestation) and delivery outcome (collected within 2 weeks post-delivery)
measure: Correlation between Bacterial vaginosis-associated vaginal community state types and clearance of Chlamydia infection
timeFrame: Assessed through study completion
measure: Incidence of Preterm birth among study arms
timeFrame: At delivery
measure: Incidence of Low birthweight infants among study arms
timeFrame: Within 2 weeks post-delivery
measure: Incidence of STI in infants exposed to infection in their mothers
timeFrame: STI testing in mother and infants within 2 weeks post-delivery to a maximum of 6 weeks post-delivery
measure: Frequency of fetal loss (miscarriage or stillbirth) among study arms
timeFrame: Assessed through study completion
Other outcomes:
Locations:
city: East London
country: South Africa
facility: Buffalo City Metro
state: Eastern Cape
Study officials:
affiliation: Foundation for Professional Development
name: Andrew Medina-Marino, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: USC Keck School of Medicine - University of Southern California
name: Jeffrey Klausner, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Medina-Marino A, Cleary S, Muzny CA, Taylor C, Tamhane A, Ngwepe P, Bezuidenhout C, Facente SN, Mlisana K, Peters RPH, Klausner JD. Sexually transmitted infection screening to prevent adverse birth and newborn outcomes: study protocol for a randomized-controlled hybrid-effectiveness trial. Trials. 2022 May 24;23(1):441. doi: 10.1186/s13063-022-06400-y.