Clinical Trial of Doxycycline VS BPG for Early Syphilis (SY-DOXY)
Status:
Not yet recruiting
Trial end date:
2023-11-01
Target enrollment:
Participant gender:
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.