Doxycycline Intervention for Bacterial STI ChemoprOphylaxis (DISCO)

A Randomized Trial of Doxycycline Chemoprophylaxis for the Prevention of Sexually Transmitted Infections in Gay, Bisexual and Other Men Who Have Sex With Men (gbMSM)

There is a growing epidemic of the bacterial sexually transmitted infections (STIs) syphilis, chlamydia and gonorrhea worldwide; similarly concerning trends have been noted in Canada, where increases of over 160% have been seen in bacterial STIs over the last decade. In Canada, gay, bisexual, and other men who have sex with men (gbMSM) - including those living with HIV - are disproportionately impacted by bacterial STIs5,6These dramatic increases in bacterial STIs, the potential development of serious complications including AMR, and waning effectiveness of the promotion of conventional STI prevention tools (e.g. condoms), signals the need for novel STI prevention strategies and tools to mitigate STI-related complications. A rigorous randomized controlled trial will be conducted to compare STI PrEP vs. STI PEP and definitively assess the efficacy, safety, antimicrobial resistance profiles and costs associated with doxycycline-based STI prevention.

Study Overview

• Status: Recruiting
• Conditions: Bacterial Sexually Transmitted Diseases
• Intervention / Treatment: Drug: Doxycycline Hyclate

Detailed Description

With the rising rates of STIs among gbMSM populations in Canada, there is an urgent need for novel interventions to prevent significant sequelae (e.g. neurosyphilis) and onward transmission of untreated infections. Despite longstanding public health efforts to encourage conventional strategies of STI prevention, gbMSM continue to bear the burden of syphilis which poses synergistic effects in the transmission of HIV. This study will add to this field through providing the first methodologically rigorous, prospective multicentre, open-label randomized controlled trial (RCT) of doxycycline-based STI PrEP (daily 100mg doxycycline) versus STI PEP (200mg doxycycline after exposure event) for the prevention of bacterial STIs among gbMSM over 15 months (60 weeks) of follow-up with adequate power to address drug efficacy in the prevention of bacterial STIs. Beyond the determination of efficacy, our trial will provide insight to the unique challenges of medication adherence through assessing the acceptability, tolerability and safety of therapy with doxycycline. This study aims to provide health care providers one additional tool to address the burden of STIs in populations with an increased likelihood of infection.

• Study Type: Interventional
• Enrollment (Estimated): 560
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Saira Mohammed; Phone Number: 6047542171; Email: smohammed@bccfe.ca
• Study Contact Backup: Name: Troy Grennan; Phone Number: 6047075606; Email: troy.grennan@bccdc.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • Sheldon Chumir Centre
      • Contact: Grace Kwon; Email: disco@ucalgary.ca
      • Principal Investigator: Caley Shukalek, MD
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z4R4
      • Recruiting
      • BC Centre for Disease Control
      • Contact: Ramin Azmin; Phone Number: 6047075617
  • Ontario
    • Hamilton, Ontario, Canada
      • Not yet recruiting
      • St. Joseph's Healthcare Hamilton
      • Contact: Kelly Waters
      • Principal Investigator: Kevin Woodward, MD
    • Ottawa, Ontario, Canada
      • Not yet recruiting
      • The Ottawa Hospital
      • Contact: TBA
      • Principal Investigator: Paul MacPherson, MD
    • Toronto, Ontario, Canada
      • Recruiting
      • St. Michael's Hospital
      • Contact: Reva Persaud; Email: optionslab@unityhealth.to
      • Contact: Stanley Onyegbule; Email: optionslab@unityhealth.to
      • Principal Investigator: Darrell Tan, MD
  • Quebec
    • Montréal, Quebec, Canada
      • Recruiting
      • McGill University Health Centre
      • Contact: Nathalie Paisible; Email: nathalie.paisible@muhc.mcgill.ca
      • Contact: Turna Hortoglu; Email: turna.hortoglu@muhc.mcgill.ca
      • Principal Investigator: Joseph Cox, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males, ≥ 18 years of age;
2. Any sexual activity (i.e. oral sex, insertive or receptive anal sex, with or without a condom) with more than one male partner in the preceding 12 months;
3. Intention to remain sexually active with more than one male partner in the next 12 months;
4. At least one prior episode of a previously diagnosed and adequately treated syphilis, gonorrhea or chlamydia infection within 12 months prior to screening.

Exclusion Criteria:

1. Known allergy to doxycycline or tetracyclines;
2. Existing chronic or intermittent tetracycline or doxycycline use (e.g. for chronic osteomyelitis, acne).
3. Use of medications which could lower doxycycline levels, including barbiturates, phenytoin and carbamazepine.
4. Individuals currently using isotretinoin;
5. Any individual capable of becoming pregnant.

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
Experimental: STI PrEP arm; doxycycline capsules 100mg orally daily for 12 months. Though the usual treatment dose of doxycycline is 100mg twice daily	Drug: Doxycycline Hyclate; STI PrEP arm: doxycycline capsules 100mg orally daily for 12 months STI PEP arm: doxycycline 200mg orally once within 24-72 hours following each sexual encounter deemed at risk (i.e. condomless anal or oral sex), to a maximum of six pills (i.e. 600 mg total) per week
Experimental: STI PEP arm; doxycycline 200mg orally once within 24-72 hours following each sexual encounter deemed at risk (i.e. condomless anal or oral sex), to a maximum of six pills (i.e. 600 mg total) per week	Drug: Doxycycline Hyclate; STI PrEP arm: doxycycline capsules 100mg orally daily for 12 months STI PEP arm: doxycycline 200mg orally once within 24-72 hours following each sexual encounter deemed at risk (i.e. condomless anal or oral sex), to a maximum of six pills (i.e. 600 mg total) per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma doxycycyline levels to determine efficacy of doxycycline chemoprophylaxis	To determine the efficacy of doxycycline chemoprophylaxis in preventing incident bacterial STI cases (syphilis, gonorrhea, and/or chlamydia, including LGV)	60 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of STIs over time	To describe frequency of syphilis, gonorrhea, and chlamydia incident infections among participants over the study period	60 weeks
Proportion of individuals reporting grade 3 or 4 adverse events in each study arm as assessed by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events	To determine the tolerability and safety of doxycycline chemoprophylaxis	60 weeks
Proportion of participants who report acceptability, community norms and partner attitudes of STI PrEP and PEP based on responses from questionnaires	To determine the acceptability of doxycycline chemoprophylaxis	60 weeks
Change in self-reported sexual activity defined as increases in condomless sexual acts and number of sexual partners based on responses from questionnaires	To evaluate the change in sexual behaviour reported by participants over the study period	60 weeks
Proportion of individuals with evidence of tetracycline class resistance in common flora (Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae) at 24 and 48 weeks.	To evaluate antimicrobial resistance in bacterial STIs and common commensal pathogens over study period	Over 48 weeks
Proportion of cases with resistance to penicillins, tetracyclines or macrolides in syphilis, and tetracycline resistance in gonorrhea and chlamydia isolates taken from the anus, oral cavity or urethra.	To evaluate antimicrobial resistance in bacterial STIs and common commensal pathogens over study period	Over 48 weeks
Proportion of individuals with adverse event-related study drug discontinuation in each study arm	To determine the tolerability and safety of doxycycline chemoprophylaxis	Over 60 weeks
Rate of adherence to study treatment (STI PrEP vs. PEP) by participants.	To assess for superiority of doxycycline PrEP over PEP (if non-inferiority is shown)	Over 48 weeks

Collaborators and Investigators

• Sponsor: Jonathan Troy Grennan
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Troy Grennan, MD, University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): August 5, 2024
• Last Update Submitted That Met QC Criteria: August 1, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Doxycycline; Pre-exposure prophylaxis (PrEP); Sexually transmitted infections (STIs); Post-exposure prophylaxis (PEP); Gay, bisexual, men who have sex with other men (gbMSM)
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Communicable Diseases; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Urogenital Diseases; Genital Diseases; Sexually Transmitted Diseases; Sexually Transmitted Diseases, Bacterial; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: BritishCCDC3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Our results will be targeted to four main groups of stakeholders: clinicians, public health, researchers, and community.The Community-Based Research Centre for Gay Men's Health, the Canadian AIDS Treatment Information Exchange (CATIE), and the AIDS Committee of Toronto will help facilitate KTE locally and nationally. We will disseminate our findings to a large, international audience of clinicians and public-health professionals by publishing in high-impact peer-reviewed journals.

Drug and device information, study documents

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