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

Sponsor

Foundation for Professional Development (Pty) Ltd (Other)

Overall Status

Recruiting

CT.gov ID

NCT04446611

Collaborator

University of Southern California (Other), National Institutes of Health (NIH) (NIH), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), University of Cape Town (Other), University of Alabama at Birmingham (Other), Louisiana State University Health Sciences Center in New Orleans (Other)

2,500

Enrollment

Location

Arms

44.1

Anticipated Duration (Months)

56.7

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Sexually Transmitted Infection HIV/AIDS Cost-effectiveness Birth Outcomes Vaginal Microbiome Neisseria Gonorrhoeae Chlamydia Trachomatis Trichomonas Vaginalis Antenatal Care Pregnancy	Diagnostic Test: First antenatal care + test-of-cure Diagnostic Test: First antenatal care + week 30-34 gestation (no test-of-cure)	N/A

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:

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

Study Aim 3 will recruit STI positive pregnant women to investigate the relationship between the vaginal microbiome and persistent chlamydial infection in pregnant women. Specifically, the investigators aim to:

Determine the impact of the vaginal microbiota on chlamydial treatment outcomes.
Explore the natural history of the vaginal microbiome in the context of antibiotic treatment for CT infections.

This is a case-control (1:2) study of chlamydia-infected pregnant women in South Africa using vaginal specimens collected at the first antenatal care (ANC) visit and daily thereafter for 3 weeks or longer if the follow-up test-of-cure result is positive.

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 Design

Study Type:

Interventional

Anticipated Enrollment :

2500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Masking Description:

The allocation of study arm is concealed to study staff during randomization

Primary Purpose:

Screening

Official Title:

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

Actual Study Start Date :

Mar 29, 2021

Anticipated Primary Completion Date :

Nov 30, 2023

Anticipated Study Completion Date :

Nov 30, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Frequency of adverse birth outcomes among study arms [At delivery]
Adverse birth outcomes as defined by a composite measure of low birth weight and pre-term delivery as recorded in maternity case records
Change in STI prevalence between baseline (first antenatal care) and birth outcome among study arms [Change in STI between baseline (<20 weeks gestation) and delivery (approx 38-42 gestation) up to 2 weeks postdelivery]
To calculate the change in CT, NG, and TV prevalence by subtracting the prevalence at delivery from the prevalence at baseline. Generalized estimating equations to test for variation among study arms with regard to change in prevalence of CT/NG/TV between baseline and delivery will be done, adjusting for potential effect modifiers and confounding variables.
To determine the association of Bacterial vaginosis-associated CSTs and chlamydial treatment outcomes [Through study completion, an average of 1 month]
Chlamydia treatment outcomes as measured by a positive or negative chlamydial test result

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria for pregnant women:

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

Gestational age will be confirmed via ultrasound

Exclusion Criteria:

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

Inclusion criteria for Neonates:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Buffalo City Metro	East London	Eastern Cape	South Africa	5217

Sponsors and Collaborators

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

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