Closed-loop Control of Penicillin Delivery

NCT04053140 | Completed Phase 1

• 1 other identifier: 251161
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an in-house feasibility study of penicillin biosensor technology linked with closed-loop control for the automated delivery of penicillin antibiotics.

Conditions

Healthy Volunteers

Keywords

Pharmacokinetics; Penicillin G; Penicillins; Proof of Concept Study; Clinical Trial, Phase I; Microneedle array

Outcome Measures

Primary Outcomes (2)

• Assessment of the biosensors ability to track benzylpenicillin concentrations compared to observations made by microdialysis and blood sampling.

  Bland-Altman plot to describe agreement between interstitial benzylpenicillin concentrations and microneedle data.

  Up to 12 hours.

• Compare PK-PD target attainment between visits

  Compare time \> MIC between visits

  Up to 12 hours.

Study Arms (3)

Routine intermittent slow bolus

EXPERIMENTAL

The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Benzylpenicillin IV 1200mg administered every 4 hours.

Device: Microneedle array; Drug: Penicillin G_1200mg

Closed-loop control of intermittent slow bolus

EXPERIMENTAL

The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Benzylpenicillin IV administered in intermittent dosing schedule. Dosage to be determined by closed-loop algorithm. Limits set to 2400mg every 4 hours.

Device: Microneedle array and closed-loop control of penicillin delivery; Drug: Penicillin G_2400mg

Closed-loop control of continuous infusion

EXPERIMENTAL

The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Benzylpenicillin IV administered in continuous dosing schedule. Dosage to be determined by closed-loop algorithm. Initial loading dose, and limits set to 600mg/hr.

Device: Microneedle array and closed-loop control of penicillin delivery; Drug: Penicillin G_600mg/hr

Interventions

Microneedle array DEVICE

The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed.

Routine intermittent slow bolus

Microneedle array and closed-loop control of penicillin delivery DEVICE

The microneedle biosensor will be sited peripherally (on the non-dominant arm) for the duration of the study. It will then be removed. Microneedle data will be used to titrate benzylpenicillin dosage according to PK-PD target.

Closed-loop control of continuous infusion; Closed-loop control of intermittent slow bolus

Penicillin G_1200mg DRUG

Benzylpenicillin IV 1200mg administered every 4 hours.

Also known as: Benzylpenicillin

Routine intermittent slow bolus

Penicillin G_2400mg DRUG

Benzylpenicillin IV administered in intermittent dosing schedule. Dosage to be determined by closed-loop algorithm. Limits set to 2400mg every 4 hours.

Also known as: Benzylpenicillin

Closed-loop control of intermittent slow bolus

Penicillin G_600mg/hr DRUG

Benzylpenicillin IV administered in continuous dosing schedule. Dosage to be determined by closed-loop algorithm. Initial loading dose, and limits set to 600mg/hr.

Also known as: Benzylpenicillin

Closed-loop control of continuous infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult \>18 years old.
• Healthy adults, with no evidence of infection.
• Previously received penicillin with no adverse effects.

You may not qualify if:

• \< 18 years old.
• High risk of skin and soft tissue infection or local skin and soft tissue infection near sensor site.
• Hypersensitivity to adhesive strips or active dermatitis.
• Penicillin hypersensitivity or previous adverse event whilst receiving penicillin.
• Anaemia on screening bloods (defined as haemoglobin \<13 g/dL in males and \<12 g/dL in females).
• Renal impairment on screening bloods (defined as a Cockcroft-Gault creatinine clearance \<60mL/min).
• Liver impairment on screening bloods (defined as ALT, ALP or bilirubin 3x ULN).
• Implantable electronic device in-situ if wearing a microneedle array device.
• Pregnant.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

NIHR Imperial CRF

London, W12 0HS, United Kingdom

Location

Related Publications (1)

• Gowers SAN, Freeman DME, Rawson TM, Rogers ML, Wilson RC, Holmes AH, Cass AE, O'Hare D. Development of a Minimally Invasive Microneedle-Based Sensor for Continuous Monitoring of beta-Lactam Antibiotic Concentrations in Vivo. ACS Sens. 2019 Apr 26;4(4):1072-1080. doi: 10.1021/acssensors.9b00288. Epub 2019 Apr 17.

  PMID: 30950598 BACKGROUND

Related Links

• Minimally Invasive Sensing of Beta-lactam Antibiotics (MISBL)

MeSH Terms

Interventions

Penicillin G

Intervention Hierarchy (Ancestors)

Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Alison H Holmes, MD MPH MBBS

  Health Protection Research Unit in HCAI & AMR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: August 12, 2019
• Study Start: November 5, 2019
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)