Doxycycline for Syphilis

Overseen By Matthew Golden, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Antiretrovirals, Immunosuppressants, others

Disqualifiers: Neurosyphilis, Tertiary syphilis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether taking doxycycline as a single daily dose can effectively treat early-stage syphilis. Researchers aim to determine if a 200mg dose taken once daily for 14 days is as effective as the standard treatment, which typically involves splitting the dose. Participants will take the medication, perform swab tests at home, complete short surveys, and visit the clinic for follow-ups. Individuals diagnosed with early-stage syphilis, such as those with a recent rash or sore, might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that interact with doxycycline. It's best to discuss your current medications with the study team to see if they might interact.

Is there any evidence suggesting that doxycycline taken as a single daily dose is likely to be safe for humans?

Research shows that patients usually tolerate doxycycline well. Previous studies found that people taking doxycycline for various infections rarely experienced serious side effects. Common mild side effects include nausea and upset stomach, while serious reactions are rare.

Doxycycline is a well-known antibiotic often used to treat infections such as acne, respiratory infections, and urinary tract infections. It is also prescribed for individuals allergic to penicillin to treat early syphilis, typically with a twice-daily dose.

This trial tests doxycycline taken once daily instead of the usual twice-daily regimen. Since the FDA has already approved it for treating syphilis with the twice-daily schedule, it has a good safety record. However, the once-daily regimen has not been extensively studied, so this trial aims to gather more specific information on that approach. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for syphilis?

Unlike the standard of care for syphilis, which typically involves penicillin injections, doxycycline offers an oral alternative that could be more convenient and accessible, especially for those with penicillin allergies. Researchers are excited about doxycycline because it provides a non-invasive treatment option that can be self-administered, reducing the need for clinic visits. Additionally, its effectiveness in treating early syphilis with a straightforward daily pill regimen could improve patient compliance and outcomes.

What evidence suggests that doxycycline might be an effective treatment for early syphilis?

Research has shown that doxycycline effectively treats syphilis, typically administered as 100 mg twice a day for 14 days. Studies have found that about 79.2% of people respond well to this treatment. In this trial, participants will receive 200 mg once a day for 14 days to test if this regimen works just as well. The aim is to determine if this method can successfully treat early-stage syphilis with similar results. ^{6 7 8 9 10}

Who Is on the Research Team?

Travis Hunt, MD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

This trial is for individuals with early stage syphilis. Participants will take a daily dose of doxycycline, submit swabs every other day for two weeks, complete online surveys, and attend up to three clinic visits over six months. Specific eligibility criteria are not provided.

Inclusion Criteria

I have been diagnosed with syphilis.

I have been diagnosed with secondary syphilis confirmed by a positive RPR test.

Laboratory-confirmed diagnosis of early latent syphilis within one month

Exclusion Criteria

Allergy to doxycycline

I am not on any form of immunosuppression.

I am taking medication that interacts with doxycycline.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive doxycycline 200mg daily for 14 days and perform oral and rectal swabs every other day

2 weeks

2 brief online surveys

Follow-up

Participants return to the clinic for an interview and blood draw every 3 months to monitor serological response

6 months

Up to 3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Doxycycline

Trial Overview The study tests if taking doxycycline as a single daily dose of 200mg for 14 days can effectively treat early syphilis. It compares this method's effectiveness based on clinical improvement and blood test results against standard treatments recorded from the sexual health program.

How Is the Trial Designed?

Group I: Doxycycline 200mg daily for 14 days Experimental Treatment 1 Intervention

Participants diagnosed with early syphilis (primary, secondary, or early latent) with an RPR of 1:4 or greater will receive doxycycline 200mg daily to treat syphilis. Exclusions include pregnant persons, persons under 18 years of age, and persons on doxy PEP. During the two weeks of treatment, participants will perform oral and rectal swabs for syphilis, returned at the end of the 2 weeks by mail. Participants will submit brief online surveys twice over the two weeks of treatment. Repeat blood tests for syphilis, reactive plasma reagin (RPR), will be done at follow-up visits at 3 and 6 months to monitor serological response. Participants with response at the 3-month visit will not need to come to a 6-month visit.

Doxycycline is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in European Union as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in Canada as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Approved in Japan as Doxycycline for:

• Acne
• Bacterial infections
• Chlamydia
• Gonorrhea
• Lyme disease
• Malaria
• Pneumonia
• Rosacea
• Urinary tract infections

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

In a study of 34 patients treated with doxycycline for early syphilis, there were no cases of serological failure, suggesting that doxycycline is effective in treating this condition.

Compared to benzathine penicillin G (BPG), which had a 5.5% serological failure rate, doxycycline showed similar median times to successful serological responses, indicating it can be a viable alternative treatment for early syphilis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxycycline compared with benzathine penicillin for the treatment of early syphilis. Ghanem, KG., Erbelding, EJ., Cheng, WW., et al.[2013]

Doxycycline hyclate (DH) has a favorable safety profile, especially in its delayed-release form (Doryx), compared to the standard powder form (Vibramycin), making it a safer option for treating conditions like acne and rosacea.

Despite historical safety concerns associated with tetracyclines, including gastrointestinal issues and effects on tooth development, subantimicrobial dosing of DH has shown to be effective and safe for acne treatment, supporting its continued use in dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use and safety of doxycycline hyclate and other second-generation tetracyclines. Sloan, B., Scheinfeld, N.[2022]

In a study of 81 patients with syphilis treated with oral doxycycline for 28 days, the treatment showed a 100% response rate for primary syphilis and high efficacy rates of 91.7% for early syphilis, indicating that doxycycline is highly effective for these stages of the disease.

The treatment was generally safe, with only mild side effects reported in a few patients, and no significant abnormalities found in laboratory tests, suggesting that doxycycline is a well-tolerated option for syphilis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic effect of oral doxycycline on syphilis (author's transl]. Onoda, Y.[2016]

In a study of 123 HIV-infected patients treated with doxycycline and 271 treated with benzathine penicillin for early syphilis, the serological response rates were similar at both 6 months (63.4% for doxycycline vs. 72.3% for penicillin) and 12 months (65.9% for doxycycline vs. 68.3% for penicillin).

The study found that the stage of syphilis significantly influenced treatment outcomes, with patients having secondary syphilis showing a higher likelihood of achieving a positive serological response, regardless of whether they received doxycycline or penicillin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of serological response to doxycycline versus benzathine penicillin G in the treatment of early syphilis in HIV-infected patients: a multi-center observational study. Tsai, JC., Lin, YH., Lu, PL., et al.[2022]

Two HIV-infected patients with asymptomatic neurosyphilis were successfully treated with high-dose oral doxycycline (200 mg twice daily for 28 days), showing significant improvements in their cerebrospinal fluid (CSF) markers and VDRL titers.

This study suggests that oral doxycycline may be a safe and effective alternative to traditional penicillin treatments for neurosyphilis, potentially allowing for outpatient management without hospitalization, although further prospective trials are needed to confirm its long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral doxycycline for treatment of neurosyphilis in two patients infected with human immunodeficiency virus. Kang-Birken, SL., Castel, U., Prichard, JG.[2022]

In a retrospective study of 163 syphilis patients treated with doxycycline, the serological response rates were high across different stages of syphilis, with 100% in primary, 96.9% in secondary, 91.3% in early latent, and 79.2% in late latent syphilis after 12 months.

The overall serological response rate was 92.4% for patients who completed the treatment and follow-up, indicating that doxycycline is an effective alternative treatment for syphilis, particularly in earlier stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Doxycycline in the Treatment of Syphilis. Dai, T., Qu, R., Liu, J., et al.[2018]

In a study of 82 patients treated for syphilis, doxycycline showed a slightly lower success rate in reducing serological markers compared to benzathine penicillin, particularly in late and indeterminate infections, suggesting that penicillin remains the more effective first-line treatment.

Doxycycline, while a second-line treatment option, may lead to a higher rate of serofast reactions in patients with latent or indeterminate syphilis, indicating potential challenges in achieving complete resolution of the infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of serological treatment response to doxycycline versus benzathine penicillin in syphilis infections, a retrospective single-center study. Zengarini, C., Carpanese, MA., Vara, G., et al.[2022]

In a study of 601 patients with early syphilis, doxycycline was found to be as effective as benzathine penicillin G in achieving serological response at both 6 and 12 months after treatment.

Despite concerns about declining efficacy, the results indicate that doxycycline remains a viable second-line treatment option for early syphilis, with no significant differences in treatment outcomes compared to the standard penicillin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Doxycycline and Benzathine Penicillin G for the Treatment of Early Syphilis. Xiao, H., Liu, D., Li, Z., et al.[2018]

In a study involving 111 healthy volunteers, enteric-coated doxycycline hyclate pellets in capsules were found to cause significantly fewer gastrointestinal adverse reactions compared to doxycycline monohydrate tablets, with only 43% of participants reporting side effects versus 66% for monohydrate.

The new formulation demonstrated improved tolerability, particularly reducing incidents of abdominal pain, nausea, and vomiting, making it a safer option for patients requiring doxycycline therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enteric Coating Reduces Upper Gastrointestinal Adverse Reactions to Doxycycline. Järvinen, A., Nykänen, S., Paasiniemi, L., et al.[2018]

Citations

1. cdc.gov cdc.gov/std/treatment-guidelines/p-and-s-syphilis.htm

P&S Syphilis - STI Treatment Guidelines Doxycycline (100 mg orally 2 times/day for 14 days) (600,601) and tetracycline (500 mg orally 4 times/day for 14 days) have been used for years ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5192147/

Efficacy of Doxycycline in the Treatment of Syphilis - PMC There are few data about doxycycline treatment in late latent syphilis patients. Our study showed that the response rate was 79.2%. Of note ...

3. cdc.gov cdc.gov/std/treatment-guidelines/latent-syphilis.htm

Latent Syphilis - STI Treatment Guidelines The only acceptable alternatives for treating late latent syphilis or syphilis of unknown duration are doxycycline (100 mg orally 2 times/day) ...

4. emedicine.medscape.com emedicine.medscape.com/article/229461-treatment

Syphilis and Treponematosis Treatment & Management Doxycycline is the best alternative for treating early and late latent syphilis. Syphilis associated with HIV infection does not require any enhanced ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27795370/

Efficacy of Doxycycline in the Treatment of Syphilis Our study showed excellent treatment outcomes in patients with different stages of syphilis. Our data, along with those from other reports, ...

6. vionausa.com vionausa.com/wp-content/uploads/2022/03/SDS-Doxycycline-Capsules.pdf

Safety Data Sheet DOXYCYCLINE HYCLATE CAPSULES ... Syphilis – early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks. Syphilis of more ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK555888/

Doxycycline Hyclate - StatPearls - NCBI Bookshelf - NIH This course explores doxycycline's mechanism of action, bioavailability, tissue penetration, and safety profile. The adverse effects and rising ...

8. drugs.com drugs.com/doxycycline.html

Doxycycline: Uses, Dosage, Side Effects, Warnings Doxycycline is used for bacterial infections, including acne, rosacea, urinary and respiratory tract infections, eye infections, gum disease, gonorrhea, ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/050006s082,050007s023,050480s047,050533s038lbl.pdf

69-1680-32-Vibramycin - Calcium (doxycycline calcium oral ... Doxycycline is a light- yellow crystalline powder. Doxycycline hyclate is soluble in water, while doxycycline monohydrate is very slightly soluble in water.

10. mayoclinic.org mayoclinic.org/drugs-supplements/doxycycline-oral-route/description/drg-20068229

Doxycycline (oral route) - Side effects & dosage It works by killing bacteria or preventing their growth. However, this medicine will not work for colds, flu, or other virus infections.