One injection vs. three': Clinical evaluation of a single, high dose subcutaneous infusion of benzathine penicillin G for treatment of syphilis (SCIP Syphilis)

Australia is currently in the midst of a syphilis epidemic which began a decade ago. Benzathine penicillin G (BPG) is the treatment of choice for non-CNS syphilis infections. Primary, secondary or early latent syphilis is treated with 2.4 million units (MU) of BPG, while late latent syphilis requires 2.4 MU weekly for 3 weeks in total. BPG is typically administered by IM injection which is associated with significant pain and distress in the recipient. This has been shown to negatively impact adherence, especially where multiple doses are indicated. Subcutaneous (SC) administration of BPG is a potentially more efficacious alternative to IM injection. Prior work done by our group in healthy adult volunteers have demonstrated acceptable tolerability and a superior pharmacokinetic profile. Our study aims to demonstrate the safety and tolerability of a single 7.2MU dose of BPG given as a subcutaneous infusion for treatment of syphilis. Secondary objectives are to demonstrate efficacy of SC BPG and estimate duration that plasma penicillin concentrations remain above the target of 18mg/mL. Primary outcome is the assessment of safety and tolerability including serious adverse events or reactions. Secondary outcomes are the change in nontreponemal specific serology titre at 6 months, plasma penicillin concentrations at 3 weeks and proportion of patients with treatment failure requiring re-treatment at 6 months. We will recruit 40 adult patients with confirmed syphilis infection from those referred to the sexual health service at Fremantle Hospital. The study will also incorporate a qualitative component exploring patient's experience and perception of receiving subcutaneous infusion. Participants will be followed up for 6 months from day of treatment. If we are successful in demonstrating safety, tolerability and efficacy of SC high dose penicillin in non-CNS syphilis infections, this has the potential to radically transform the treatment paradigm.