A Randomized Controlled Trial of Doxycycline Post Exposure Prophylaxis to Prevent Incident Bacterial STIs Among Women in the United States

The bacterial sexually transmitted infections (STIs) chlamydia, gonorrhea, and syphilis cause multiple adverse outcomes in women, and prevention strategies are critically needed. This project will determine the efficacy of doxycycline post-exposure prophylaxis (doxy PEP) to prevent STIs among women through a phase IV, open-label, randomized controlled trial.

Study Overview

• Status: Not yet recruiting
• Conditions: Prevention; Prophylaxis; Adherence; Syphilis Female; Gonorrhea Female; Chlamydia Females
• Intervention / Treatment: Drug: Doxycycline; Other: Standard of Care (SOC)

Detailed Description

The bacterial sexually transmitted infections (STIs) chlamydia (CT), gonorrhea, and syphilis cause multiple adverse outcomes in women, and rates of these infections have increased dramatically over the past two decades. Prevention of these infections is now possible with the use of doxycycline post-exposure prophylaxis (doxy PEP), which has demonstrated efficacy in multiple studies conducted among men from high prevalence groups. However, only one trial of the use of doxy PEP (dPEP Kenya) has been conducted among women, and unfortunately this study had a null result. Our proposed project seeks to evaluate doxy PEP efficacy among women in the United States through an open-label, randomized controlled trial (RCT) conducted in three jurisdictions (New Orleans, LA; Birmingham, AL; Chicago, IL) with high STI prevalence. Close adherence monitoring is critical given that the dPEP Kenya study's null result was likely related to poor medication adherence; thus, this trial will monitor and reinforce doxycycline adherence throughout the study using a novel PCheck app developed by our team, test urines for doxycycline levels on all participants, and hair on a nested cohort. The study's aim to conduct an RCT in 519 sexually active, non-pregnant women aged 18-35, randomizing 2:1 to better evaluate adverse events related to doxy PEP, powering the study on CT as the most commonly anticipated STI; sensitivity analyses will compare CT rates based on adherence measured by doxycycline levels in urine and by self-reported pill-taking. To execute these aims, we have assembled a multidisciplinary team with extensive expertise in the conduct of clinical trials, bioinformatics, biostatistics, infectious diseases epidemiology, STI prevention, the vaginal microbiome, behavioral health interventions, and qualitative science. MPIs Clement, Kissinger, and Muzny collectively have decades of collaborative experience enrolling priority populations in large clinical trials aimed to improve sexual health outcomes. Ultimately, this trial has the potential to have substantial public health impact, leading to a novel bacterial STI prevention intervention to reduce the undue burden of incident bacterial STIs among women.

• Study Type: Interventional
• Enrollment (Estimated): 519
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female
• Aged 18-35

• Reporting condomless vaginal sex with men AND least one of the following:

  1. diagnosis of CT, gonorrhea, syphilis, or trichomonas in the past year
  2. reporting 2 or more sexual partners in the past 6 months
• Plan to continue to be sexually active over the next year
• Have smartphone and be willing to engage with an app
• If HIV+: Viral load<200 copies/ml and CD4 count >200 cells/mm3

Exclusion Criteria:

• Pregnant, nursing, or intending to become pregnant
• Reported allergy to tetracyclines
• Liver disease or end-stage renal disease
• Non-English Speaking
• Taking concomitant medications which may impact doxycycline metabolism (e.g., systemic retinoids, antacids, barbiturates, carbamazepine, phenytoin, iron, warfarin, rifampin)
• Not willing to take doxy PEP or comply with study procedures
• Unable to provide informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; 200 mg oral doxy PEP (N=346)	Drug: Doxycycline; Enrolled participants will be randomized 2:1 to receive 200 mg of doxy PEP taken within 24 hours of condomless sex versus standard of care. Only one trial of the use of doxy PEP (dPEP Kenya) has been conducted among women, and unfortunately this study had a null result.; Other Names: Doxy PEP
Active Comparator: Control; Standard of care (i.e. no doxy PEP, N=173)	Other: Standard of Care (SOC); Enrolled participants will be randomized 2:1 to receive 200 mg of doxy PEP taken within 24 hours of condomless sex versus standard of care. Only one trial of the use of doxy PEP (dPEP Kenya) has been conducted among women, and unfortunately this study had a null result.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
chlamydia incidence	The primary outcome will be the number of CT infections over person-time (incidence rate).	Participants will be evaluated at baseline and quarterly for 48 weeks with STI testing at each visit.

Collaborators and Investigators

• Sponsor: Tulane University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); University of Alabama at Birmingham; Louisiana State University Health Sciences Center in New Orleans

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): April 1, 2032

Study Registration Dates

• First Submitted: July 10, 2026
• First Submitted That Met QC Criteria: July 10, 2026
• First Posted (Actual): July 15, 2026

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Health Services Administration; Health Care Quality, Access, and Evaluation; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Quality of Health Care; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Quality Indicators, Health Care; Naphthacenes; Tetracyclines; Doxycycline; Standard of Care
• Other Study ID Numbers: R01AI196614

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: STI lab tests results, surveys results from baseline and quarterly visits, app data, doxycycline drug levels by urinalysis, doxycycline hair levels
• IPD Sharing Access Criteria: Data will be shared in dedicated data repositories. The selected repositories will provide a persistent unique identifier for the datasets such as a Digital Object Identifier (DOI) or accession number. The unique identifiers will be included in associated publications. Dataset submission will be populated with keywords to maximize findability of the datasets. Access to the shared data will be free and unrestricted. Persons who wish to access raw data will need to send a written request to the MPIs (Drs. Kissinger, Muzny, and Clement), providing them with an explanation of the reason for the request. This request will be reviewed by the MPIs and, if deemed appropriate, submitted to the IRB of record for approval.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes