Superiority of On-demand PrEP Versus PEP on Using Doxycycline for Preventing STI in MSM

Superiority of On-demand Pre-exposure Prophylaxis Versus Post-exposure Prophylaxis on Using Doxycycline for Preventing Sexually Transmitted Infections in Men Who Have Sex With Men

The goal of this clinical trial is to compare the effectiveness of doxycycline taken for on-demand pre-exposure prophylaxis (DoxyODPrEP) and its post-exposure use (DoxyPEP) in preventing bacterial sexually transmitted infections (STI), including chlamydia, gonorrhoea, and syphilis among men who have sex with men (MSM). The main questions it aims to answer are:

1. Is DoxyODPrEP superior to DoxyPEP?
2. Are both regimens safe?
3. Does the MSM community accept the use of doxycycline to prevent bacterial STI?

Participants will be asked to take doxycycline according to the study arm they are randomly assigned to, and attend regular clinical follow-ups during the 2-year observation period. Researchers will compare the bacterial STI incidences between the two groups to see if DoxyODPrEP is superior to DoxyPEP.

Study Overview

• Status: Active, not recruiting
• Conditions: Chlamydia; Gonorrhea; Sexually Transmitted Diseases, Bacterial; Syphilis
• Intervention / Treatment: Drug: DoxyODPrEP; Drug: DoxyPEP

Detailed Description

Participants would be randomly assigned to either DoxyODPrEP or DoxyPEP arm, and be instructed to take doxycycline with the respective dosing schedule. They would be followed up for 24 months for nucleic acid amplification test (NAAT) and antibody tests against bacterial STI, namely chlamydia, gonorrhoea, and syphilis. The subjects and investigators would not be blinded due to its open-label nature, as the two arms' dosing schedules are different. Participants in the DoxyODPrEP arm would be instructed to take two doxycycline hyclate 100mg capsules orally 2-24 hours before sex, and one 100mg capsule each 24 and 48 hours after loading dose. If they have sex within 48 hours after the loading dose, they would be asked to continue a daily 100mg until two days after the last sex. Participants in the DoxyPEP arm would be instructed to take two doxycycline hyclate 100mg capsules orally within 24 hours and up to 72 hours after each sex. At each clinic visit, urine, and pharyngeal and rectal swabs would be self-collected on-site by the participants following instructions. Pill count would be performed for each follow-up visit.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • Stanley Ho Centre for Emerging Infectious Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• has had sex with another male in the past six months
• normally reside in Hong Kong
• can communicate in written and spoken Chinese or English
• willing and able to give written informed consent
• being willing and able to attend scheduled study clinic visits
• at risk of STI (had condomless sex with more than one man in the past 12 months, history of STI diagnosis in the past 12 months, inclination to have condomless sex, and other HIV-PrEP-eligible criteria)

Exclusion Criteria:

• Being allergic to tetracycline class medicines
• Currently taking medications that are contraindicated with doxycycline
• Using antibiotics for more than 14 days in the month preceding enrolment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DoxyODPrEP; Participants in the DoxyODPrEP arm would be instructed to take two doxycycline hyclate 100mg capsules orally 2-24 hours before sex, and one 100mg capsule each 24 and 48 hours after loading dose. If they have sex within 48 hours after the loading dose, they would be asked to continue a daily 100mg until two days after the last sex.	Drug: DoxyODPrEP; Participants in the DoxyODPrEP arm would be instructed to take two doxycycline hyclate 100mg capsules orally 2-24 hours before sex, and one 100mg capsule each 24 and 48 hours after loading dose. If they have sex within 48 hours after the loading dose, they would be asked to continue a daily 100mg until two days after the last sex; Other Names: doxycycline on demand PrEP
Active Comparator: DoxyPEP; Participants in the DoxyPEP arm would be instructed to take two doxycycline hyclate 100mg capsules orally within 24 hours and up to 72 hours after each sex.	Drug: DoxyPEP; Participants in the DoxyPEP arm would be instructed to take two doxycycline hyclate 100mg capsules orally within 24 hours and up to 72 hours after each sex.; Other Names: doxycycline PEP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the first episode of gonorrhoea after the enrolment visit	Time to the first episode of gonorrhoea after the enrolment visit	Months 1 to 24
Time to the first episode of chlamydia after the enrolment visit	Time to the first episode of chlamydia after the enrolment visit	Months 1 to 24
Time to the first episode of syphilis after the enrolment visit	Time to the first episode of syphilis after the enrolment visit	Months 1 to 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile	Percentage of participants experiencing adverse events and the associated grades	Months 1 to 24
Acceptability of regimens	Percentage of participants accepted the regimen	Months 1 to 24
Retention	Percentage of participants remained during the follow-up period	Months 1 to 24
Time to the first episode of HIV after the enrolment visit	Time to the first episode of HIV after the enrolment visit	Months 1 to 24

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Tsz Ho Kwan, PhD, Jockey Club School of Public Health and Primary Care

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: December 18, 2023
• First Submitted That Met QC Criteria: December 18, 2023
• First Posted (Actual): January 3, 2024

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: men who have sex with men; doxycycline; sexually transmitted infections
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Chlamydiaceae Infections; Neisseriaceae Infections; Treponemal Infections; Pathological Conditions, Signs and Symptoms; Behavior; Sexual Behavior; Sexuality; Sexually Transmitted Diseases; Sexually Transmitted Diseases, Bacterial; Chlamydia Infections; Gonorrhea; Syphilis; Homosexuality; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Doxycycline
• Other Study ID Numbers: 23220262

Drug and device information, study documents

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