Pharmacokinetics and Safety of Antimicrobial Agents Administered by Subcutaneous Route in Patients AGEd Over 65 Years

Older People Clinical Trial

— PhASAge  

Official title:

Pharmacokinetics and Safety of Antimicrobial Agents Administered by Subcutaneous Route in Patients AGEd Over 65 Years

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03583749
• Other study ID #: CHUBX 2017/37
• Status: Recruiting
• Start date: August 7, 2019
• Est. completion date: September 5, 2021

Study information

• Verified date: February 2021
• Source: University Hospital, Bordeaux
• Contact: Claire ROUBAUD-BAUDRON, MD, PhD
• Phone: +33 (0) 5 57 82 18 44
• Email: claire.roubaud[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Elderly people are more prone to develop infection with a poorer prognosis compared to young people. Physicians may encounter difficulties regarding antimicrobial agents administration route. In fact, poor venous access and behavioral disturbance are frequent issues. The subcutaneous (SC) route may be a safe alternative, but sparse data are available in the literature. The present study aims to describe Pharmacokinetics (PK) / Pharmacodynamics (PD) characteristics of antibiotics (amoxicillin/clavulanate, ceftriaxone and piperacillin/tazobactam) subcutaneous administration in patients aged over 65.

Description:

Antibiotic administration through subcutaneous (SC) injection is common practice in France, especially in Geriatrics as an alternative to intravenous (IV) route in case of poor venous access or delirium (Forestier et al. CMI 2015). Whereas tolerance of such a practice seems to be reasonable (Roubaud-Baudron et al. Age and Ageing 2017), sparse PK/PD data are available. Most PK/PD studies include young and healthy subjects, yet elderly patients often have multimorbidity , poly medication, renal insufficiency and cachexia which may disturb antibiotics PK/PD. Compared to intravenous (IV) route, SC route is less painful and less frequently associated with infectious or thrombotic complication. A recent study carried out in Bordeaux University Hospital comparing PK/PD data on ertapenem SC or IV administrations in patients aged over 75 showed that area under the curve (AUC) and probability to maintain free ertapenem concentration above the Minimum inhibitory concentration (MIC) during at least 40% of time (fT>MIC>40%) were not significantly different (manuscript in progress).

The investigator's hypothesis is that SC administration of amoxicillin-clavulanate, ceftriaxone and piperacillin-tazobactam has favorable pharmacokinetics and acceptable tolerance compared with IV infusion in elderly patients.

Patients receiving one of the three antibiotics by IV or SC route will be included at steady state (depending on antibiotic treatment) for several blood tests (3 or 4 depending of routes choice) and followed until 15 days after completion of antibiotic treatment in order to evaluate tolerance and efficacy of antibiotic treatment. Physicians in charge of patients will decide antibiotic prescription including administration route. The study will not influence these choices because patients will be included after antibiotic initiation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: September 5, 2021
• Est. primary completion date: September 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Aged over 65

• To receive ceftriaxone (1g daily) or amoxicillin-clavulanate (1g/0.2g every 8h) or piperacillin-tazobactam (4g/0.5g every 8h) by SC or IV infusion (30-60minutes) at steady state (48h, 24h and 24h respectively)

• Free, written and informed consent signed by the participant or by a proxy in case of delirium

Exclusion Criteria:

• criteria for legislation (justice protection, subject participating to another research including a period of exclusion)

• previous inclusion in this study

Related Conditions & MeSH terms

• Antibiotic
• Antimicrobials
• Older People
• Subcutaneous Injection

Intervention

Drug:
• Subcutaneous (SC) route for antibiotic treatment
Patients receiving one of the three antibiotics by SC route without any randomization because the route will be chosen before inclusion by the physician in charge.
• Intravenous (IV) route for antibiotic treatment
Patients receiving one of the three antibiotics by IV route without any randomization because the route will be chosen before inclusion by the physician in charge.

Locations

Country	Name	City	State
France	CHU de Bordeaux	Bordeaux
France	Hospital Métropole Savoie	Chambéry
France	CHU de Grenoble Alpes	Grenoble
France	Hospices Civils de Lyon	Lyon
France	University Hospital, Poitiers	Poitiers

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma antibiotic concentrations	Describe and compare pharmacokinetics of amoxicillin-clavulanate, ceftriaxone and piperacillin-tazobactam administered by SC and IV routes	Day 1
Secondary	Number of adverse events	Occurrence of adverse events (AEs) up to 15 days after the end of local antibiotherapy (edema, pain, erythema, necrosis) and systemic (AEs described in the Summary of Product Characteristics for antibiotics)	Day 21
Secondary	Number of infection cure	rate of infection cure at the end of antibiotic treatment up to 15 days after the end of antibiotic therapy	Day 21
Secondary	Number of hospitalisation days	Describe the times of hospitalisation	Day 21