Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000333516
Ethics application status
Approved
Date submitted
28/02/2024
Date registered
26/03/2024
Date last updated
26/03/2024
Date data sharing statement initially provided
26/03/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
SCIP RHD: Subcutaneous injection of benzathine Penicillin G (BPG) in people with rheumatic fever
Scientific title
Safety, tolerability and acceptability of high dose, subcutaneous injection of benzathine penicillin G (Bicillin® L-A) in children and young adults with rheumatic fever
Secondary ID [1] 311624 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record
This study is linked to ACTRN12622000916741

Health condition
Health condition(s) or problem(s) studied:
rheumatic fever 333057 0
rheumatic heart disease 333058 0
Condition category
Condition code
Cardiovascular 329739 329739 0 0
Other cardiovascular diseases
Infection 329740 329740 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.

Intervention code [1] 328080 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 337527 0
To measure adherence to long-term (18 months) high dose Bicillin® L-A administered by subcutaneous injection.
Timepoint [1] 337527 0
18 months post-baseline
Primary outcome [2] 337528 0
To measure the time (in days) that penicillin concentrations remain above the minimum inhibitory concentration (0.02mg/mL) for Streptococcus pyogenes following high dose Bicillin® L-A administered by subcutaneous injection.
Timepoint [2] 337528 0
Every 70-91 days across an 18-month period post baseline.
Secondary outcome [1] 432219 0
To compare prior adherence to intramuscular BPG to adherence to subcutaneous injection of BPG.
Timepoint [1] 432219 0
One year prior to starting subcutaneous injections and one year of being on subcutaneous injections.

Eligibility
Key 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.
Minimum age
6 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/06/2023
Date of last participant enrolment
Anticipated
31/08/2025
Actual
Date of last data collection
Anticipated
28/02/2027
Actual
Sample size
Target
65
Accrual to date
20
Final
Recruitment outside Australia
Country [1] 26179 0
New Zealand
State/province [1] 26179 0

Funding & Sponsors
Funding source category [1] 315946 0
Charities/Societies/Foundations
Name [1] 315946 0
Te Niwha
Country [1] 315946 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Country
New Zealand
Secondary sponsor category [1] 318084 0
None
Name [1] 318084 0
Address [1] 318084 0
Country [1] 318084 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314777 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 314777 0
https://ethics.health.govt.nz/about/southern-health-and-disability-ethics-committee/
Ethics committee country [1] 314777 0
New Zealand
Date submitted for ethics approval [1] 314777 0
08/05/2023
Approval date [1] 314777 0
25/05/2023
Ethics approval number [1] 314777 0

Summary
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).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132690 0
Dr Julie Bennett
Address 132690 0
University of Otago, 23A Mein Street, Newtown, Wellington 6021
Country 132690 0
New Zealand
Phone 132690 0
+64 21321993
Fax 132690 0
Email 132690 0
julie.bennett@otago.ac.nz
Contact person for public queries
Name 132691 0
Julie Bennett
Address 132691 0
University of Otago, 23A Mein Street, Newtown, Wellington 6021
Country 132691 0
New Zealand
Phone 132691 0
+64 21321993
Fax 132691 0
Email 132691 0
julie.bennett@otago.ac.nz
Contact person for scientific queries
Name 132692 0
Julie Bennett
Address 132692 0
University of Otago, 23A Mein Street, Newtown, Wellington 6021
Country 132692 0
New Zealand
Phone 132692 0
+64 21321993
Fax 132692 0
Email 132692 0
julie.bennett@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will not be made publicly available.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.