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

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.

Study Overview

• Status: Recruiting
• Conditions: Older People; Antimicrobials; Subcutaneous Injection; Antibiotic
• Intervention / Treatment: Drug: Subcutaneous (SC) route for antibiotic treatment; Drug: Intravenous (IV) route for antibiotic treatment

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.

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: Claire ROUBAUD-BAUDRON, MD, PhD; Phone Number: +33 (0) 5 57 82 18 44; Email: claire.roubaud@chu-bordeaux.fr
• Study Contact Backup: Name: Aurélie CHERCHOULY; Phone Number: +33 (0) 5 24 54 91 86; Email: aurelie.cherchouly@chu-bordeaux.fr

Study Locations

• France
  • Bordeaux, France, 33000
    • Recruiting
    • CHU de Bordeaux
    • Contact: Claire ROUBAUD-BAUDRON, MD, PhD; Phone Number: +335 57 65 66 10; Email: claire.roubaud@chu-bordeaux.fr
  • Chambéry, France, 73000
    • Recruiting
    • Hospital Métropole Savoie
    • Contact: Emmanuel FORESTIER, MD; Phone Number: +33 (0) 4 79 96 51 72; Email: emmanuel.forestier@ch-metropole-savoie.fr
    • Principal Investigator: Emmanuel Forestier, MD
  • Grenoble, France, 38700
    • Recruiting
    • CHU de Grenoble Alpes
    • Contact: Gaëtan GAVAZZI, MD, PhD; Phone Number: +334 76 76 57 97; Email: ggavazzi@chu-grenoble.fr
    • Principal Investigator: Gaëtan GAVAZZI, MD, PhD
  • Lyon, France, 69000
    • Recruiting
    • Hospices Civils de Lyon
    • Principal Investigator: Tristan FERRY, MD, PhD
    • Contact: Tristan FERRY, MD, PhD; Phone Number: +334 72 07 11 07; Email: tristan.ferry@chu-lyon.fr
  • Poitiers, France, 86021
    • Recruiting
    • University Hospital, Poitiers
    • Contact: Marc PACCALIN, MD, PhD; Email: Marc.PACCALIN@chu-poitiers.fr
    • Principal Investigator: Marc PACCALIN, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
amoxicillin-clavulanate; followed of SC and IV cohort without any randomization because the route will be chosen before inclusion by the physician in charge.	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.; Drug: 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.
ceftriaxone; followed of SC and IV cohort without any randomization because the route will be chosen before inclusion by the physician in charge.	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.; Drug: 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.
piperacillin-tazobactam; followed of SC and IV cohort without any randomization because the route will be chosen before inclusion by the physician in charge.	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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma antibiotic concentrations	Describe and compare pharmacokinetics of amoxicillin-clavulanate, ceftriaxone and piperacillin-tazobactam administered by SC and IV routes	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Number of hospitalisation days	Describe the times of hospitalisation	Day 21

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Claire ROUBAUD-BAUDRON, MD, PhD, Hospital University, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2019
• Primary Completion (Anticipated): September 5, 2021
• Study Completion (Anticipated): September 5, 2021

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (Actual): July 11, 2018

Study Record Updates

• Last Update Posted (Actual): February 16, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: safety; elderly; pharmacokinetics; Antimicrobial agents; subcutaneous administration
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: CHUBX 2017/37

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No