None listed
Conditions
Brief summary
Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) almost exclusively affect Indigenous Maori and Pacific children and young adults living in socio-economically deprived areas of the North Island in Aotearoa, New Zealand. Across the Tasman, the associated morbidity from RHD is the leading driver of cardiovascular inequality for Indigenous Australians. For 70 years, the only proven way to prevent ARF progression has been benzathine penicillin G (BPG), given as a monthly intramuscular (IM) injection. The effectiveness of this approach is limited by pain and the frequency of injection which leads to sub-optimal adherence. There is an urgent need to improve penicillin formulations for all children living with ARF/RHD. Based on previous work we have shown that penicillin can be delivered as an ‘implant’ if given as a high-dose subcutaneous (SC) infusion, which allows for sustained penicillin concentrations (>3 months). This approach fulfils the ideal product characteristics for the next generation of long-acting penicillin. Our Phase I trial (ACTRN12621000135819) showed that SCIP was tolerable and provided sustained penicillin concentrations in healthy adults and our Phase II trial (ACTRN12622000916741) has shown that children and young adults who are currently receiving monthly BPG injections for their ARF/RHD, prefer to have Bicillin ®L-A delivered by subcutaneous injection every 70/91 days (depending on weight). This study will follow a cohort of children and young adults who wish to remain on Bicillin ®L-A delivered by subcutaneous injection across an extended timeframe (minimum one-year).
Interventions
This is a Phase II trial to test the safety, tolerability, acceptance, and pharmaco-equivalence of high dose subcutaneous Bicillin® L-A in children and young adults living with rheumatic fever and regularly receiving intramuscular benzathine penicillin G (BPG) injections. 70 to 91 days after the participants have taken part in ACTRN12622000916741, they will be offered the opportunity to remain on high dose (11.5mL/13.8MIU-20.7mL/10.8MIU) subcutaneous injection of Bicillin® L-A as an alternative
This is a Phase II trial to test the safety, tolerability, acceptance, and pharmaco-equivalence of high dose subcutaneous Bicillin® L-A in children and young adults living with rheumatic fever and regularly receiving intramuscular benzathine penicillin G (BPG) injections. 70 to 91 days after the participants have taken part in ACTRN12622000916741, they will be offered the opportunity to remain on high dose (11.5mL/13.8MIU-20.7mL/10.8MIU) subcutaneous injection of Bicillin® L-A as an alternative to their regular monthly intramuscular BPG injection. Subcutaneous injection of high dose Bicillin, will be administered by the study nurse every 70-91 days for a period of 18 months. Electronic medical records will be utilised to monitor adherence to the high dose Bicillin.
Sponsors
University of Otago
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Aged 6 years of age or older with a prior diagnosis of rheumatic fever or rheumatic heart disease. Currently on secondary prophylaxis. No prior documented allergy to penicillin, cephalosporin antibiotics. Normally reside in New Zealand.
Exclusion criteria
History of adverse drug reaction or hypersensitivity. Planned absence from their usual place of residence during the study trial. History within the last 12 months of intramuscular, or subcutaneous injection of the abdominal wall, or history of surgery to the buttocks, abdomen or abdominal wall within the last 12 months. Pregnancy. Scarring or superficial changes on the abdomen. Dermatological conditions that affect the abdomen.
Outcome results
None listed