How does the absorption of benzathine penicillin G (BPG) used for Group A Streptococcus (GAS) treatment and secondary prophylaxis for rheumatic fever (RF) differ when injected into the fat layer compared to injection in the muscle in healthy adult men?
Determining the rate of absorption of intramuscular versus subcutaneous administration of Benzathine Penicillin G (BPG) in healthy adult males using ultrasound guidance in a single -blinded 2x2 crossover trial with a 10-week washout period.
Telethon Kids Institute
15 participants
Sep 2, 2018
Interventional
Conditions
Summary
This study aims to determine if delivering a standard dose of 1,200,000 units of benzathine penicillin G (BPG) into the fat layer rather than the recommended injection deep into the muscle will result in slower absorption of penicillin into the blood stream, and if the slower absorption results in the penicillin lasting longer above the level needed to prevent infection with the bacteria Streptococcus pyogenes that is responsible for the development of sore throats, skin sores, blood stream infections and the delayed autoimmune conditions of glomerulonephritis and rheumatic fever. The healthy male volunteers recruited for the study will received 2 injections of BPG 10-weeks apart; one into the fat layer of the buttock and the other into the muscles of the buttock. The injections will be guided by ultrasound scan. The volunteers will be randomised at first injection, i.e. they will not know or be able to tell if the injection was into muscle or the fat layer. Measuring the blood penicillin levels will be carried out using drops of blood from a finger prick which will be stored on filter paper -dry blood spots (DBS) and analysed together at the end of the study. Pain which is a recognised side effect of the injection into the muscles will assessed along with other unwanted side effects to determine the safety of injecting BPG into the fat layer. A follow up ultrasound of the injection site to look for any changes that are not visible externally will also be conducted to document what happens around the injection site. The objectives of this study will be assessed through DBS collection, pain scores associated with receiving study drug subcutaneously and intramuscularly, adverse events assessments, safety blood collection and physical examination.
Eligibility
Inclusion Criteria5
- (a) Healthy male aged 18 - 65 years at the time of screening.
- (b) BMI between 18.5kg/m2 and 26.0kg/m2.
- (c) No history of chronic renal impairment or significant liver dysfunction.
- (d) Participants who are considered likely to adhere to the trial guidelines for the duration of the trial.
- (e) Sign and dated informed consent
Exclusion Criteria6
- (a) Currently taking penicillin or use of penicillin-based antibiotics from screening to final study visit
- (b) Known penicillin or soy allergy
- (c) History of significant hip or gluteal surgery
- (d) Use of any prescription medication or over-the-counter medication, herbal products, vitamins or minerals within 7 days prior to study drug administration until completion of the final follow up visit
- (e) Participation in another clinical 3 months preceding the trial or planned participation in another clinical trial concurrently
- (f) Histroy of tobacco use within 1 month of screening.
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Interventions
15 healthy adult males will be randomised in a single-blinded 2x2 crossover trial to receive a first dose 1,200,000 Units of BPG administered via the standard deep intramuscular route or the subcutaneous route under ultrasound guidance with a 10-week washout period (sampling will occur for 6 weeks to monitor penicillin levels, pain and adverse effects and follwed by a rest period of 4 weeks before they repeat the cycle using the alternate route of injection for the second dose of 1,200,000 Units of BPG and a further 6 weeks of similar follow up). Blood levels of benzylpenicillin will be measured at pre-determined time intervals around each injection using dry blood spots (13 points) and plasma level (2 points for quality assurance) to determine the rate of absortion, time above the minimum inhibitory concentration (MIC) for Streptococcus pyogenes and duration of measureable benzylpenicllin levels above the limit of quantification of the analyser. Pain and other adverse events will be reported and monitored to determine the safety and adverse effect profile of BPG. Ultrasound will used 4-weeks after each injection to document the number and types of local changes. Summary of study periods: Dosing day Period 1 (IM or SC) --> 6 weeks sampling --> 4 weeks rest --> Dosing Day Period 2 (Alternate route SC or IM) --> 6 weeks sampling --> 2 weeks end of study phone call. Sampling Intervals around each of the injections: Dry blood spot sampling: 0 hours (prre-injection/baseline), 2 hours, 6 hours, 12 hours (+ QC venous PK sample), 24 hours, 48 hours, 72 hours, 5 days, 7 days, 14 days (+ QC venous PK sample), 21 days, 28 days (with ultrasound scan of injection site), 42 days.
Locations(1)
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ACTRN12618001435279