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

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if doxycycline taken as 200mg daily for 14 days is effective to treat early stage syphilis. This is different from how doxycycline is typically used for syphilis because the full doxycycline dose will be taken at the same time of day, rather than split up into a twice daily regimen. Lab data support that taking the medication as a single daily dose should be effective as treatment, but it has not been studied clinically. The main question this study aims to answer is: Is doxycycline taken as a single daily dose of 200mg for 14 days an effective treatment for early syphilis based on a combined outcome of clinical improvement and blood test improvement? Participants will: 1. Take doxycycline 200mg daily for 14 days 2. Submit oral and rectal swabs that test for syphilis bacteria every other day for 2 weeks, returned by mail 3. Complete 2 brief online surveys over the first 2 weeks 4. Return to the clinic for an interview and blood draw every 3 months for a maximum of 3 study visits, including the first visit The investigators will compare the percentage of participants in the study who have response to treatment by 6 months to that of persons who have received standard (CDC-recommended) regimens. To do this, the investigators will calculate response percentage estimates following a shot of long-acting penicillin or 14 days of doxycycline 100mg twice daily from 60-person samples from the sexual health program's records.

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 doxycycline an effective drug for treating syphilis?

Doxycycline is considered a good alternative to penicillin for treating syphilis, especially when penicillin is not an option. Studies show that it has high success rates in treating early stages of syphilis, although it may be less effective for late latent syphilis compared to penicillin. ^{1 2 3 4 5}

Is doxycycline safe for treating syphilis?

Doxycycline is generally safe for treating syphilis, with few notable side effects. Some patients may experience mild stomach discomfort, but serious side effects are rare. Enteric-coated formulations can reduce stomach-related issues. ^{1 4 6 7 8}

How does the drug doxycycline differ from other treatments for syphilis?

Doxycycline is an oral antibiotic used as a second-line treatment for syphilis, especially when penicillin cannot be used. It is taken in pill form, which can be more convenient than the intramuscular injection required for penicillin, but it may have a slightly lower success rate, particularly in late-stage syphilis. ^{1 2 3 4 9}

Research Team

Travis Hunt, MD

Principal Investigator

University of Washington

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Doxycycline compared with benzathine penicillin for the treatment of early syphilis. [2013]

2. Croatia pubmed.ncbi.nlm.nih.gov

Comparison of Doxycycline and Benzathine Penicillin G for the Treatment of Early Syphilis. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Analysis of serological treatment response to doxycycline versus benzathine penicillin in syphilis infections, a retrospective single-center study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Doxycycline in the Treatment of Syphilis. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Oral doxycycline for treatment of neurosyphilis in two patients infected with human immunodeficiency virus. [2022]

6. England pubmed.ncbi.nlm.nih.gov

The use and safety of doxycycline hyclate and other second-generation tetracyclines. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

Enteric Coating Reduces Upper Gastrointestinal Adverse Reactions to Doxycycline. [2018]

9. United States 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. [2022]