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

Pregnancy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04446611
• Other study ID #: R01AI149339
• Secondary ID: R01AI149339
• Status: Recruiting
• Phase: N/A
• Start date: March 29, 2021
• Est. completion date: April 30, 2025

Study information

• Verified date: January 2023
• Source: Foundation for Professional Development (Pty) Ltd
• Contact: Andrew Medina-Marino, PhD, MPH
• Phone: +27 43 726 7538
• Email: AndrewM[@]foundation.co.za
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 2500
• Est. completion date: April 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Antenatal Care
• Birth Outcomes
• Chlamydia Infections
• Chlamydia Trachomatis
• Cost-effectiveness
• Gonorrhea
• HIV Infections
• HIV/AIDS
• Neisseria Gonorrhoeae
• Pregnancy
• Sexually Transmitted Diseases
• Sexually Transmitted Infection
• Trichomonas Infections
• Trichomonas Vaginalis
• Vaginal Microbiome

Intervention

Diagnostic Test:
• First antenatal care + test-of-cure
Single point-in-time molecular point-of-care diagnostic screening and treatment for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis at first antenatal care visit and infection-specific test-of-cure 3 weeks post-treatment. Women with a positive test-of-cure will be re-treated. As CT/NG is a combined Xpert test, women who present with an incident infection (newly diagnosed infection) will be treated and managed accordingly.
• First antenatal care + week 30-34 gestation (no test-of-cure)
Repeated molecular point-of-care diagnostic screening and treatment for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis at first antenatal care visit and at week 30-34 gestation. No test-of-cure will be conducted for women with positive test results; however, additional treatment will be provided to women with persistent/recurrent vaginal discharge.

Locations

Country	Name	City	State
South Africa	Buffalo City Metro	East London	Eastern Cape

Sponsors (7)

Lead Sponsor	Collaborator
Foundation for Professional Development (Pty) Ltd	Louisiana State University Health Sciences Center in New Orleans, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), University of Alabama at Birmingham, University of Cape Town, University of Southern California

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse birth outcomes among study arms	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	Recorded within 2 weeks of delivery
Secondary	Change in STI prevalence (a) between baseline visit and delivery within the experimental arms and (b) between the experimental and control arms by 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	Between baseline (first antenatal visit <27 weeks' gestation) and delivery outcome (collected within 2 weeks post-delivery)
Secondary	Correlation between Bacterial vaginosis-associated vaginal community state types and clearance of Chlamydia infection	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.	Assessed through study completion
Secondary	Incidence of Preterm birth among study arms	The frequency of live births before 37 weeks' gestation, as validated by ultrasound dating at first antenatal visit	At delivery
Secondary	Incidence of Low birthweight infants among study arms	The frequency of live births with birth weight < 2500g, as recorded in the maternity case records	Within 2 weeks post-delivery
Secondary	Incidence of STI in infants exposed to infection in their mothers	Frequency of Chlamydia, Gonorrhoeae, and/or Trichomonas infection among infants born to a mother in whom infection is detected post-delivery	STI testing in mother and infants within 2 weeks post-delivery to a maximum of 6 weeks post-delivery
Secondary	Frequency of fetal loss (miscarriage or stillbirth) among study arms	Composite frequency of miscarriage (<28 weeks' gestation) or stillbirth (> 28 weeks' gestation) and the individual components, as indicated in the maternal case records	Assessed through study completion