Chlamydia trachomatis is a common infection that can be contracted through sexual activity. Doctors typically use a medication called doxycycline to treat it, but some prefer azithromycin because it's easier to take. The aim of this study is to investigate whether a shorter duration of doxycycline treatment (3 days) is just as effective as the longer duration (7 days). If this shorter duration of treatment is found to be as effective as the standard 7-day treatment, it is anticipated that uptake of doxycycline for treatment of chlamydia will become more widespread. This will lead to better individual and public health outcomes compared to the current widespread use of azithromycin at a lower cost with more judicious antibiotic use than a 7-day doxycycline treatment duration.

The study will take place in the United States and Kenya and approximately 664 participants will take part in the study across these different locations. The study will recruit potential participants utilizing in-person outreach by staff members in our Community Section, which handles recruitment and retention activities for the Pwani Research Centre.  Community Section staff will conduct recruitment activities in collaboration with our Community Advisory Board. Potential participants will be invited to the site for consenting purposes. Once informed consent is obtained, participants’ demographic data will be collected. Visit procedures such as medical history, physical exams, laboratory samples (urine, vaginal and rectal swabs) will be collected. Thereafter, those who qualify to join the study will be randomly assigned to either the short course treatment or the longer course treatment. Participants will be followed up for one month. Those who will receive the 3-day treatment will also get placebo pills for 4 days, allowing blinding of both participants and investigators to the treatment arm. Participants who are eligible take part in the study will be required to adhere to all visit procedures and visit schedules if they wish to participate. Those who are not eligible will end the study at that point.

This study may bring about minor inconvenience or discomfort for participants. Collecting samples might cause temporary discomfort, and asking about sexual history might induce mild stress. Participating might involve sacrificing some privacy, but the study team will prioritize keeping information confidential. Participants' personal information that may identify them won't be disclosed in any study reports, documents, or to unauthorized personnel. If the 3-day treatment turns out to be less effective than the 7-day treatment, individuals in the 3-day group might still have some remaining infection that could worsen. However, the study team will closely monitor this possibility and provide the standard of care treatment (7 days longer course treatment) in the event of treatment failure.

Participants may receive additional medical care and tests as part of the study including extra checks for symptoms and counseling on risk reduction for acquisition and transmission of sexually transmitted infections (STIs) and HIV. This study will contribute to our understanding of better ways to treat this infection and use antibiotics wisely, benefiting society as a whole.

The study was expected to begin in late 2023, with each participant involved for about 29 days. The entire study will take around 25 months. Currently we expect to start the study in March 2024.

The 2021 revised Center for Disease and Control (CDC) sexually transmitted infection (STI) treatment guidelines recommend doxycycline as the preferred treatment for chlamydia trachomatis (CT) in most populations. The extent to which this recommendation will be translated into practice remains to be seen since many clinicians prefer to use azithromycin due to the relative ease of a single dose treatment. The rationale for studying a 3-day course (100 mg oral twice daily) as an alternate treatment is that this length of therapy is likely to provide sufficient treatment based on what is known about the life cycle of CT and pharmacokinetics (PK) of doxycycline, as well as preliminary clinical data. The CT life cycle is 48-72 hours, and the serum half-life of doxycycline is 18-22 hours. Thus, a 3-day course (72 hours) should provide sufficient coverage to eliminate CT. A small RCT compared the 3-day versus 7- day course of doxycycline for CT (N=73) in women with chlamydial cervicitis in the mid-1990s (Reedy et al., 1997). In that study, the proportion of women who cleared their chlamydial infection was nearly identical among women randomized to 3-day (94.3% cure) versus 7-day (94.7% cure) doxycycline.

This is a non-inferiority study design, which is a study that tests whether a new treatment is no worse than the standard-of-care treatment to which it is being compared. In this study we will test whether a shorter course of treatment for CT (100 mg doxycycline twice daily for 3 days) is no worse than the current standard-of-care (100 mg doxycycline twice daily for 7 days). Participants randomized to 3-days of doxycycline will receive 4 days of placebo pills (the medication will be labeled so that participants will take the active medication on days 1-3 and placebo on days 4-7). Placebo pills will be included for this arm so that participants are blinded to the arm to which they were randomized, thereby minimizing the likelihood that participants randomized to the 3-day arm will systematically resume sexual activity sooner than those randomized to the 7-day arm. There is no arm that will receive only placebo since a safe and effective treatment for CT already exists.

This study will examine the non-inferiority of a 3-day regimen of doxycycline compared to the recommended 7-day regimen. If this shorter regimen is found to be non-inferior to the standard 7-day regimen, it is anticipated that uptake of doxycycline for CT treatment will become more widespread, leading to better individual and public health outcomes compared to widespread use of azithromycin at a lower cost with more judicious antibiotic use than a 7-day doxycycline regimen.