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

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ClinicalTrials.gov Identifier: NCT03583749
Recruitment Status : Not yet recruiting
First Posted : July 11, 2018
Last Update Posted : July 11, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux

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.

Condition or disease Intervention/treatment
Antimicrobials Subcutaneous Injection Antibiotic Older People 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.


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Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Pharmacokinetics and Safety of Antimicrobial Agents Administered by Subcutaneous Route in Patients AGEd Over 65 Years
Estimated Study Start Date : September 30, 2018
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : October 20, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics

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.




Primary Outcome Measures :
  1. Plasma antibiotic concentrations [ Time Frame: Day 1 ]
    Describe and compare pharmacokinetics of amoxicillin-clavulanate, ceftriaxone and piperacillin-tazobactam administered by SC and IV routes


Secondary Outcome Measures :
  1. Number of adverse events [ Time Frame: Day 21 ]
    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)

  2. Number of infection cure [ Time Frame: Day 21 ]
    rate of infection cure at the end of antibiotic treatment up to 15 days after the end of antibiotic therapy

  3. Number of hospitalisation days [ Time Frame: Day 21 ]
    Describe the times of hospitalisation


Biospecimen Retention:   Samples Without DNA

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.



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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03583749


Contacts
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Contact: Claire ROUBAUD-BAUDRON, MD +33 (0) 5 57 82 18 44 claire.roubaud@chu-bordeaux.fr
Contact: Fara RATSIMBAZAFY +335 (0) 57 65 65 71 fara.ratsimbazafy@chu-bordeaux.fr

Locations
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France
CHU de Bordeaux Not yet recruiting
Bordeaux, France, 33000
Contact: Claire ROUBAUD-BAUDRON, MD    +335 57 65 66 10    claire.roubaud@chu-bordeaux.fr   
Principal Investigator: Claire ROUBAUD-BAUDRON, MD         
Hospital Métropole Savoie
Chambéry, France, 73000
CHU de Grenoble Alpes Not yet recruiting
Grenoble, France, 38700
Contact: Gaëtan GAVAZZI, MD, PhD    +334 76 76 57 97    ggavazzi@chu-grenoble.fr   
Hospices Civils de Lyon Not yet recruiting
Lyon, France, 69000
Contact: Tristan FERRY, MD, PhD    +334 72 07 11 07    tristan.ferry@chu-lyon.fr   
Principal Investigator: Tristan FERRY, MD, PhD         
University Hospital, Poitiers
Poitiers, France, 86021
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
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Principal Investigator: Claire ROUBAUD-BAUDRON, MD Hospital University, Bordeaux

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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT03583749     History of Changes
Other Study ID Numbers: CHUBX 2017/37
First Posted: July 11, 2018    Key Record Dates
Last Update Posted: July 11, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Bordeaux:
Antimicrobial agents
subcutaneous administration
safety
pharmacokinetics
elderly
Additional relevant MeSH terms:
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Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents