Doxycycline Intervention for Bacterial STI ChemoprOphylaxis (DISCO)

Sponsor
Jonathan Troy Grennan (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT04762134
Collaborator
Canadian Institutes of Health Research (CIHR) (Other)
447
3
48

Study Details

Study Description

Brief Summary

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 definitively assess the efficacy, safety, antimicrobial resistance profiles and costs associated with doxycycline-based STI prevention

Condition or Disease Intervention/Treatment Phase
  • Drug: Doxycycline Hyclate
Phase 2/Phase 3

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) and STI PEP (200mg doxycycline after exposure event) versus standard-of-care 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 Design

Study Type:
Interventional
Anticipated Enrollment :
447 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomization with a 1:1:1 ratioRandomization with a 1:1:1 ratio
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
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)
Anticipated Study Start Date :
Apr 1, 2021
Anticipated Primary Completion Date :
Mar 31, 2025
Anticipated Study Completion Date :
Mar 31, 2025

Arms and Interventions

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

No Intervention: Control/Standard of care arm

routine STI screening and care, which for sexually active gbMSM would not include any chemoprophylaxis for STI, as no clinical guidelines currently recommend its use

Outcome Measures

Primary Outcome Measures

  1. Plasma doxycycyline levels to determine efficacy of doxycycline chemoprophylaxis [60 weeks]

    To determine the efficacy of doxycycline chemoprophylaxis in preventing incident bacterial STI cases (syphilis, gonorrhea, and/or chlamydia, including LGV)

Secondary Outcome Measures

  1. Frequency of STIs over time [60 weeks]

    To describe frequency of syphilis, gonorrhea, and chlamydia incident infections among participants over the study period

  2. 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 [60 weeks]

    To determine the tolerability and safety of doxycycline chemoprophylaxis

  3. Proportion of participants who report acceptability, community norms and partner attitudes of STI PrEP and PEP based on responses from questionnaires [60 weeks]

    To determine the acceptability of doxycycline chemoprophylaxis

  4. Change in self-reported sexual activity defined as increases in condomless sexual acts and number of sexual partners based on responses from questionnaires [60 weeks]

    To evaluate the change in sexual behaviour reported by participants over the study period

  5. Proportion of individuals with evidence of tetracycline class resistance in common flora (Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae) at 24 and 48 weeks. [Over 48 weeks]

    To evaluate antimicrobial resistance in bacterial STIs and common commensal pathogens over study period

  6. 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. [Over 48 weeks]

    To evaluate antimicrobial resistance in bacterial STIs and common commensal pathogens over study period

  7. Proportion of individuals with adverse event-related study drug discontinuation in each study arm [Over 60 weeks]

    To determine the tolerability and safety of doxycycline chemoprophylaxis

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Jonathan Troy Grennan
  • Canadian Institutes of Health Research (CIHR)

Investigators

  • Principal Investigator: Troy Grennan, MD, University of British Columbia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Jonathan Troy Grennan, Principal Investigator, British Columbia Centre for Disease Control
ClinicalTrials.gov Identifier:
NCT04762134
Other Study ID Numbers:
  • BritishCCDC3
First Posted:
Feb 21, 2021
Last Update Posted:
Feb 21, 2021
Last Verified:
Feb 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Jonathan Troy Grennan, Principal Investigator, British Columbia Centre for Disease Control
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 21, 2021