Clinical trial NCT04762134: Doxycycline Intervention for Bacterial STI ChemoprOphylaxis (DISCO)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bacterial Sexually Transmitted Diseases
Keywords: Sexually transmitted infections (STIs)
Doxycycline
Pre-exposure prophylaxis (PrEP)
Post-exposure prophylaxis (PEP)
Gay, bisexual, men who have sex with other men (gbMSM)
Lead sponsor: British Columbia Centre for Disease Control
Sponsor class: OTHER_GOV
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2021-02-21
Enrollment: 560
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization with a 1:1 ratio
Primary purpose: PREVENTION

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 compare STI PrEP vs. STI PEP and definitively assess the efficacy, safety, antimicrobial resistance profiles and costs associated with doxycycline-based STI prevention.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Plasma doxycycyline levels to determine efficacy of doxycycline chemoprophylaxis
timeFrame: 60 weeks
Secondary outcomes:
measure: Frequency of STIs over time
timeFrame: 60 weeks
measure: 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
timeFrame: 60 weeks
measure: Proportion of participants who report acceptability, community norms and partner attitudes of STI PrEP and PEP based on responses from questionnaires
timeFrame: 60 weeks
measure: Change in self-reported sexual activity defined as increases in condomless sexual acts and number of sexual partners based on responses from questionnaires
timeFrame: 60 weeks
measure: Proportion of individuals with evidence of tetracycline class resistance in common flora (Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae) at 24 and 48 weeks.
timeFrame: Over 48 weeks
measure: 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.
timeFrame: Over 48 weeks
measure: Proportion of individuals with adverse event-related study drug discontinuation in each study arm
timeFrame: Over 60 weeks
measure: Rate of adherence to study treatment (STI PrEP vs. PEP) by participants.
timeFrame: Over 48 weeks
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Sheldon Chumir Centre
state: Alberta
city: Vancouver
country: Canada
facility: BC Centre for Disease Control
state: British Columbia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
Study officials:
affiliation: University of British Columbia
name: Troy Grennan, MD
role: PRINCIPAL_INVESTIGATOR
References: