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

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



Sponsors


Source

University Hospital, Bordeaux

Oversight Info

Has Dmc

No

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


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.

Overall Status

Not yet recruiting

Start Date

2018-09-30

Completion Date

2020-10-20

Primary Completion Date

2020-09-30

Study Type

Observational

Primary Outcome

Measure

Time Frame

Plasma antibiotic concentrations
Day 1

Secondary Outcome

Measure

Time Frame

Number of adverse events
Day 21
Number of infection cure
Day 21
Number of hospitalisation days
Day 21

Number Of Groups

3

Enrollment

150

Conditions


Intervention

Intervention Type

Drug

Intervention Name


Description

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.

Arm Group Label

amoxicillin-clavulanate

ceftriaxone

piperacillin-tazobactam



Intervention Type

Drug

Intervention Name


Description

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.

Arm Group Label

amoxicillin-clavulanate

ceftriaxone

piperacillin-tazobactam




Eligibility

Study Pop

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

Sampling Method

Non-Probability Sample

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

Gender

All

Minimum Age

65 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Claire ROUBAUD-BAUDRON, MD
Principal Investigator
Hospital University, Bordeaux

Overall Contact

Last Name

Claire ROUBAUD-BAUDRON, MD

Phone

+33 (0) 5 57 82 18 44

Email



Location

Facility

Status

Contact

Investigator

CHU de Bordeaux
Bordeaux 33000 France
Not yet recruiting
Last Name: Claire ROUBAUD-BAUDRON, MD
Phone: +335 57 65 66 10
Email: [email protected]
Last Name: Claire ROUBAUD-BAUDRON, MD
Role: Principal Investigator
Hospital Métropole Savoie
Chambéry 73000 France
CHU de Grenoble Alpes
Grenoble 38700 France
Not yet recruiting
Last Name: Gaëtan GAVAZZI, MD, PhD
Phone: +334 76 76 57 97
Email: [email protected]
Hospices Civils de Lyon
Lyon 69000 France
Not yet recruiting
Last Name: Tristan FERRY, MD, PhD
Phone: +334 72 07 11 07
Email: [email protected]
Last Name: Tristan FERRY, MD, PhD
Role: Principal Investigator
University Hospital, Poitiers
Poitiers 86021 France

Location Countries

Country

France


Verification Date

2018-06-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Sponsor


Keywords


Has Expanded Access

No

Intervention Browse

Mesh Term

Anti-Bacterial Agents

Antibiotics, Antitubercular

Anti-Infective Agents



Arm Group

Arm Group Label

amoxicillin-clavulanate

Description

followed of SC and IV cohort without any randomization because the route will be chosen before inclusion by the physician in charge.


Arm Group Label

ceftriaxone

Description

followed of SC and IV cohort without any randomization because the route will be chosen before inclusion by the physician in charge.


Arm Group Label

piperacillin-tazobactam

Description

followed of SC and IV cohort without any randomization because the route will be chosen before inclusion by the physician in charge.



Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Fara RATSIMBAZAFY

Phone

+335 (0) 57 65 65 71

Email



Biospec Retention

Samples Without DNA

Biospec Descr

The sampling times chosen are the following:

- C0: concentration measured at the end of the therapeutic interval, just before the
following infusion, which corresponds to the minimum or residual concentration

- Cperf: concentration measured at the end of infusion: immediately after stopping the
infusion, which corresponds to the maximum concentration IV

- C5h: concentration measured in the elimination phase, 5h after the end of the infusion.
For the subcutaneous route only, an additional sample will be taken:

- C2h: concentration measured 2h after the end of the SC infusion.

The tubes will then be processed in the local pharmacokinetic laboratory as follows:

For each antibiotic, the blood samples obtained from each recruitment center will be
transported, centrifuged, aliquoted and frozen at the local pharmacology laboratory. The
tubes will then be batched to the centralized transport dosing laboratory every 6 months.

Acronym

PhASAge

Patient Data

Sharing Ipd

No


Firstreceived Results Disposition Date

N/A

Study Design Info

Observational Model

Case-Only

Time Perspective

Prospective


Study First Submitted

June 28, 2018

Study First Submitted Qc

July 10, 2018

Study First Posted

July 11, 2018

Last Update Submitted

July 10, 2018

Last Update Submitted Qc

July 10, 2018

Last Update Posted

July 11, 2018


ClinicalTrials.gov processed this data on July 11, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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