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

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

Study Overview

• Status: Recruiting
• Conditions: HIV/AIDS; Pregnancy; Cost-effectiveness; Antenatal Care; Chlamydia Trachomatis; Vaginal Microbiome; Birth Outcomes; Sexually Transmitted Infection; Neisseria Gonorrhoeae; Trichomonas Vaginalis
• Intervention / Treatment: Diagnostic test: First antenatal care + test-of-cure; Diagnostic test: First antenatal care + week 30-34 gestation (no test-of-cure)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 2500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrew Medina-Marino, PhD, MPH; Phone Number: +27 43 726 7538; Email: AndrewM@foundation.co.za
• Study Contact Backup: Name: Jeffrey Klausner, MD, MPH; Phone Number: +1 323-442-1100; Email: jdklausner@med.usc.edu

Study Locations

• South Africa
  • Eastern Cape
    • East London, Eastern Cape, South Africa, 5217
      • Recruiting
      • Buffalo City Metro
      • Contact: Andrew Medina-Marino, PhD, MPH; Phone Number: +27 43 726 7538; Email: AndrewM@foundation.co.za
      • Principal Investigator: Andrew Medina-Marino, PhD, MPH
      • Principal Investigator: Jeffrey Klausner, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test at 1st ANC + Test-of-Cure (Treatment 1); Single point-in-time diagnostic screening plus test-of-cure three weeks post-treatment	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.
Experimental: Test at 1st ANC + 30-34 gestation (Treatment 2); Repeated diagnostic screening at first antenatal care and 30-34 weeks gestation	Diagnostic test: 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.
No Intervention: Syndromic Management (Control); Syndromic management (standard of care) at every antenatal care visit per South African National Guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Foundation for Professional Development (Pty) Ltd
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); University of Alabama at Birmingham; National Institutes of Health (NIH); University of Southern California; Louisiana State University Health Sciences Center in New Orleans; University of Cape Town
• Investigators: Principal Investigator: Andrew Medina-Marino, PhD, MPH, Foundation for Professional Development; Principal Investigator: Jeffrey Klausner, MD, MPH, USC Keck School of Medicine - University of Southern California

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2021
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): April 30, 2025

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 25, 2020

Study Record Updates

• Last Update Posted (Estimate): January 6, 2023
• Last Update Submitted That Met QC Criteria: January 4, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Pregnancy; Sexually transmitted infection; South Africa; HIV/AIDS; Antenatal care; Chlamydia trachomatis; Neisseria gonorrhoeae; Birth outcomes; Vaginal microbiome; Trichomonas vaginalis; Diagnostic testing
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Parasitic Diseases; Protozoan Infections; Slow Virus Diseases; Neisseriaceae Infections; Chlamydiaceae Infections; Sexually Transmitted Diseases, Bacterial; HIV Infections; Acquired Immunodeficiency Syndrome; Chlamydia Infections; Gonorrhea; Sexually Transmitted Diseases; Trichomonas Infections
• Other Study ID Numbers: R01AI149339 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Access Criteria: Based on contractual agreement
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No