High dose, subcutaneous injections of benzathine penicillin G (SCIP) to prevent rheumatic fever: A single arm, phase IIa trial of safety and pharmacokinetics — ASN Events
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  2. Plenary 5 - Interventions for Prevention
  3. High dose, subcutaneous injections of benzathine penicillin G (SCIP) to prevent rheumatic fever: A single arm, phase IIa trial of safety and pharmacokinetics

High dose, subcutaneous injections of benzathine penicillin G (SCIP) to prevent rheumatic fever: A single arm, phase IIa trial of safety and pharmacokinetics (116419)

Julie Bennett 1 , Sam Salman 2 , Dhevindri Moodley 1 , Hazel Dobinson 3 , Erik Andersen 3 , Anneka Anderson 4 , Brioni Moore 5 , Madhu Page-Sharp 5 , Kevin Batty 5 , Jonathan R Carapetis 6 , Michael G Baker 1 , Joesph H Kado 6 , Laurens H Manning 6
  1. Department of Public Health, University of Otago, Wellington, New Zealand
  2. Internal Medicine, University of Western Australia, Perth, Western Australia, Australia
  3. Department of Paediatrics, Te Whatu Ora - Capital, Coast and Hutt Valley, Wellington, New Zealand
  4. Te Kupenga Hauroa Maori, University of Auckland, Auckland, New Zealand
  5. Curtin Medical School, Curtin University, Perth, Western Australia, Australia
  6. The Kids Research Institute Australia, Perth, Western Australia, Australia

Since the 1950s, benzathine penicillin G (BPG) has been administered as four-weekly intramuscular (IM) injections in patients with acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Penicillin concentrations remain detectable between injections to protect against Group A Streptococcal (GAS) infections and RHD progression. Pain, fear, and injection frequency are common reasons for poor adherence. To improve adherence and prevent progression, there is an urgent need for new secondary prevention strategies. This Phase-IIa trial evaluates the safety and pharmacokinetics of high-dose, 10-weekly subcutaneous penicillin (SCIP) in young people with ARF/RHD.

Participants received 7.2-10.8MU (13.8-20.7 mL) of Bicillin-LA® via SCIP in Wellington, New Zealand. A subset underwent intensive safety monitoring and serial dried blood spot collection for penicillin assay. Penicillin concentrations informed a population pharmacokinetic model based on 169 data points from 31 participants. Proportion of time penicillin concentrations remained above a range of plausible target pharmacological correlates of protection (10-20 ng/mL) was estimated for SCIP and compared with IM BPG.

Fifty-five participants, aged 7-44 years, received SCIP at least once, totaling 182 doses. SCIP was well tolerated, with one mild adverse event and no recurrent ARF or breakthrough GAS throat infections. SCIP outperformed IM BPG in simulations across nearly all targets. SCIP performed even more favorably when considering modified weight-based dosing or missed IM BPG injections.

SCIP (Bicillin-LA®) is safe and well tolerated, demonstrating favorable penicillin exposure for most individuals. Future research should explore the effectiveness of SCIP over longer periods and in diverse populations and settings including powdered formulations.

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