Clinical trial NCT03583749: Pharmacokinetics and Safety of Antimicrobial Agents Administered by Subcutaneous Route in Patients AGEd Over 65 Years
Official title: Pharmacokinetics and Safety of Antimicrobial Agents Administered by Subcutaneous Route in Patients AGEd Over 65 Years
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Antimicrobials
Subcutaneous Injection
Antibiotic
Older People
Keywords: Antimicrobial agents
subcutaneous administration
safety
pharmacokinetics
elderly
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2018-07-11
Enrollment: 150
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be included during their hospitalization. They may be included if they receive first-line antibiotic treatment or other antibiotic therapy, as long as the time to reach pharmacokinetic steady state has been reached. This project involves patients hospitalized in an infectious and tropical or geriatric ward

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma antibiotic concentrations
timeFrame: Day 1
Secondary outcomes:
measure: Number of adverse events
timeFrame: Day 21
measure: Number of infection cure
timeFrame: Day 21
measure: Number of hospitalisation days
timeFrame: Day 21
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Chambéry
country: France
facility: Hospital Métropole Savoie
city: Grenoble
country: France
facility: CHU de Grenoble Alpes
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Poitiers
country: France
facility: University Hospital, Poitiers
Study officials:
affiliation: Hospital University, Bordeaux
name: Claire ROUBAUD-BAUDRON, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: