Doxycycline PEP for Prevention of Sexually Transmitted Infections Among Kenyan Women Using HIV PrEP (dPEP-KE)

• ClinicalTrials.gov Identifier: NCT04050540
• Recruitment Status: Active, not recruiting
• First Posted: August 8, 2019
• Last Update Posted: August 9, 2023
• Sponsor: University of Washington
• Collaborators: Kenya Medical Research Institute; Kenya National AIDS & STI Control Programme; University of California, San Francisco; National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): Jared Baeten, University of Washington

Tracking Information

• First Submitted Date: August 6, 2019
• First Posted Date: August 8, 2019
• Last Update Posted Date: August 9, 2023
• Actual Study Start Date: February 5, 2020
• Actual Primary Completion Date: October 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 6, 2019)

Incidence of N. gonorrhoeae, C. trachomatis, or early syphilis infection by laboratory-based diagnosis [ Time Frame: 12 months post enrolment ]

Combined incidence of N. gonorrhoeae, C. trachomatis, or early syphilis infection by by laboratory-based diagnosis (e.g., positive N. gonorrhoeae or C. trachomatis based on NAAT or syphilis based on four-fold increase in non-treponemal titers).

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Doxycycline PEP for Prevention of Sexually Transmitted Infections Among Kenyan Women Using HIV PrEP
• Official Title: PrEP and dPEP: Doxycycline Post-exposure Prophylaxis for Prevention of Sexually Transmitted Infections Among Kenyan Women Using HIV Pre-exposure Prophylaxis
• Brief Summary: This is a randomized clinical trial of doxycycline post-exposure prophylaxis (dPEP) to reduce bacterial STIs among Kenyan women taking pre-exposure prophylaxis (PrEP). The overarching goal is to assess the effectiveness of dPEP on incidence of STIs while also balancing acceptability, cost, and impact on tetracycline resistance to inform public health policy. Participants will be randomized to receive dPEP and standard of care or the standard of care only. Questionnaires, focus group discussions, SMS, and in-depth interviews will be used to study acceptability and changes sexual behavior due to dPEP.

Detailed Description

This study is an open-label 1:1 randomized clinical trial of doxycyline PEP to reduce bacterial STIs - Neisseria gonorrhoeae, Chlamydia trachomatis, and T. pallidum (syphilis) - among Kenyan women taking PrEP. Participants will be counseled about the preliminary effectiveness data from IPERGAY, and the potential for resistance in STIs or other bacteria.

The primary study objectives are to 1) evaluate the effectiveness of doxycycline PEP (dPEP) to reduce STI infections in HIV-uninfected Kenyan women taking HIV PrEP; 2) assess the safety, tolerability, and acceptability of dPEP; 3)assess adherence to dPEP; 4) investigate the impact of dPEP on tetracycline resistance in N. gonorrhoeae and C. trachomatis; 5) measure the cost of dPEP and estimate the cost per case averted, budget impact, and affordability

Subjects will be randomized 1:1 to dPEP versus standard of care; randomization will be done in variable-sized blocks and using opaque envelopes opened at randomization. Participants assigned to dPEP will be instructed to take doxycycline 200 mg (two 100mg capsules) orally within 24 hours and up to 72 hours after each condomless sex act (consistent with IPERGAY) as frequently as daily if indicated but not more than once daily.

At Months 0,3,6 and 9, women randomized to dPEP will receive doxycycline, sufficient for up to daily use for 3 months (i.e., 180 capsules). Unused capsules will be counted at each quarterly follow-up visit and additional doxycycline will be provided. Participants will also be offered single- or multi-dose pill carriers for ease of dosing dPEP following exposures. All participants will receive quarterly visits for standard of care prevention services and collection of clinical and behavioral data, for a total of 12 months of follow-up.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• HIV Infections
• HIV/AIDS
• Neisseria Gonorrheae Infection
• Chlamydia Trachomatis Infection
• Syphilis Infection

Intervention

Drug: Doxycycline

200 mg of doxycycline to be taken orally within 24 hours and up to 72 hours after each condomless sex act

Study Arms

• Experimental: dPEP Intervention Arm
  Participants assigned to dPEP will be instructed to take doxycycline 200 mg (two 100mg capsules) orally within 24 hours and up to 72 hours after each condomless sex act
  Intervention: Drug: Doxycycline
• No Intervention: Standard of Care Arm
  Participants assigned to Standard of Care

• Publications *: Stewart J, Bukusi E, Sesay FA, Oware K, Donnell D, Soge OO, Celum C, Odoyo J, Kwena ZA, Scoville CW, Violette LR, Morrison S, Simoni J, McClelland RS, Barnabas R, Gandhi M, Baeten JM. Doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections among Kenyan women using HIV pre-exposure prophylaxis: study protocol for an open-label randomized trial. Trials. 2022 Jun 16;23(1):495. doi: 10.1186/s13063-022-06458-8.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 1, 2021): 449
• Original Estimated Enrollment (submitted: August 6, 2019): 446
• Estimated Study Completion Date: June 30, 2024
• Actual Primary Completion Date: October 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Willing and able to give written informed consent
• Age ≥18 years and ≤30 years old
• Female sex at birth
• HIV-seronegative at the time of last test within the past month and a current prescription for PrEP according to the national guidelines of Kenya (define PrEP eligibility as: partner of HIV-infected person not on ART or on ART for <6 months, >1 partner of unknown status, transactional sex, recent STI, recurrent HIV PEP use, inconsistent condom use, or injection drug use).

Exclusion Criteria:

• Pregnant
• Breastfeeding a child
• Allergy to tetracycline class
• Current medications which may impact doxycycline metabolism or that are contraindicated with doxycycline, as per the prescribing information. These include systemic retinoids, barbiturates, carbamazepine, phenytoin, and warfarin.
• Recent use of prolonged (more than 14 day course) antibiotics in the month prior to enrollment
• Active, clinically significant medical or psychiatric conditions that would interfere with study participation, at the discretion of the site investigator or designee.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 30 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Kenya

Administrative Information

• NCT Number: NCT04050540
• Other Study ID Numbers: STUDY00007487; R01AI145971 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jared Baeten, University of Washington
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Washington
• Original Study Sponsor: Same as current

Collaborators

• Kenya Medical Research Institute
• Kenya National AIDS & STI Control Programme
• University of California, San Francisco
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Jared Baeten, MD, PhD; University of Washington

• PRS Account: University of Washington
• Verification Date: August 2023