Investigators: Laurens Manning, Jonathan Carapetis, Joseph Kado, Julie Marsh
External collaborators: Andrew Steer (Menzies School of Health Research), Kevin Batty (Curtin University of Technology), Sam Salman (University of Western Australia), Josh Osowicki (Murdoch Children's Research Institute)
Rheumatic heart disease (RHD) is a global health priority. In Australia, RHD-related death and disability is the leading driver of cardiovascular inequality between Indigenous and non-Indigenous Australians. Guidelines recommend regular injections of benzathine penicillin G (BPG) to prevent Streptococcus pyogenes (Strep A) infections as one of the cornerstones of RHD control. However, due to poor acceptability, under-use of BPG contributes to the ongoing inequitable burden of RHD in Australia. Even with good adherence, BPG does not reliably prevent all episodes of acute rheumatic fever/RHD. Indeed, with standard dosing, penicillin concentrations often fall below the accepted target for more than half the time between injections. There is an urgent need to develop new penicillin formulations that are less painful, less frequent and more effective than BPG.
The CHIPS Trial is a double-blinded, randomised dose-ranging trial designed to determine the minimum effective steady-state penicillin concentrations required to prevent pharyngitis caused by Strep A. This trial will use a world-first fully validated human challenge model for Strep A infection which has been developed in Australia by members of our team as a tool to test different interventions in the fight against acute rheumatic fever (ARF) and RHD. If the CHIPS Trial determines that the minimum concentration required to prevent Strep A pharyngitis is lower than the currently accepted target of 20 ng/mL, this will transform the penicillin reformulation landscape toward a new long acting penicillin implant and provide opportunities to make data-driven changes to recommendations of currently available penicillin preparations used for secondary prophylaxis of ARF and RHD.