Clinical Trial of Doxycycline VS BPG for Early Syphilis (SY-DOXY)

Summary

According to European and US Centers for Disease Control and Prevention (CDC) guidelines, the recommended treatment for uncomplicated early syphilis in adults (i.e. primary, secondary and early latent) is a single intramuscular injection of 2.4 million units of benzathine benzylpenicillin G (BPG). Recent reviews have also recommended BPG as the first-line treatment of early syphilis, reporting a success rate of more than 90% over a large panel of studies. This form of the drug provides weeks of treponemicidal levels of penicillin in the blood, but does not efficiently cross the blood-brain barrier.

However, despite the use of BPG for almost 70 years and its status as the gold standard treatment for early syphilis, the need to administer this antibiotic parenterally has led to the use of second-line oral antibiotics, including firstgeneration macrolides, and then second-generation macrolides, such as azithromycin. Several African studies have shown 1 g azithromycin bid treatment for one day to be effective against early syphilis, but most authors agree that azithromycin should not generally be used as resistance to this macrolide is highly prevalent in Western countries. Moreover, a recent study by our group showed that more than 80% of the treponemal strains isolated in France harbor the mutation conferring resistance to azithromycin. The use of this alternative would, therefore, be highly unlikely to be effective in France. Tetracycline antibiotics have also been proposed as an alternative in patients with a contraindication for BPG or other forms of penicillin. Doxycycline, at a dose of 100 mg orally twice daily for 14 days, has been endorsed as a preferred alternative treatment, but few data are available concerning its efficacy. This issue is crucial, for two main reasons: there has been a recrudescence of early syphilis in most western countries over the last 20 years, increasing the need for BPG, and two periods of BPG shortage were experienced in 2013 and 2017, leading to the use of alternative treatments due to the temporary unavailability of BPG or its limitation to cases in which no other treatment was possible. Data for the manufacturing and distribution of antibiotics are not publicly available, but reports of limited availability, shortages, and price increases for old antibiotics suggest that the current system is too fragile to provide what should be a given in modern medicine: access to effective treatment for common and potentially severe bacterial infections. The recurrence of BPG shortages over the last five years has created an urgent need to demonstrate that doxycycline is safe, or at least as safe as BPG, for treating early syphilis. The investigators hypothesize that the recommended doxycycline regimen is not inferior to BPG and plan to test this hypothesis in a randomized clinical trial.

Conditions

• Syphilis

Interventions

DRUG

BPG

intramuscular injection of 2.4 million units

DRUG

Doxycycline

Oral: at a dose of 100 mg bid for 14 days

Sponsors & Collaborators

• URC-CIC Paris Descartes Necker Cochin

  collaborator OTHER

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Nicolas DUPIN, PhD & MD · APHP Assistance Publique des Hôpitaux de Paris

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-12-06

Primary Completion

2025-07-23

Completion

2025-07-23

FDA Drug

Yes

Countries

• France

Study Locations