Antibiotic Dosing in Geriatric Patients At the Emergency Department

NCT ID: NCT04436991

Last Updated: 2024-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

180 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-01-03

Study Completion Date

2025-01-31

Brief Summary

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In this pilot study, we will investigate whether - with the current dosing regimens, used in the Ghent University Hospital - pharmacodynamic targets regarding beta-lactam antibiotics (more specific Amoxicilline-Clavulanate, Piperacillin-Tazobactam and Temocillin) are attained in frail patients admitted to the geriatric department.

Detailed Description

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In drug research studies, older people - and especially patients with a geriatric profile or frailty risk - are very frequently excluded. Moreover, drug dosing is often extrapolated from studies in younger adults with failure to consider potential differences in pharmacokinetics (PK) and pharmacodynamics (PD).

Studies on dosing of beta-lactam antibiotics in geriatric or frail patients aged 75 years or older have, to the best of our knowledge, never been performed.

In this pilot study, we will investigate whether - with the current dosing regimens, used in the Ghent University Hospital - pharmacodynamic targets regarding beta-lactam antibiotics (more specific Amoxicilline-Clavulanate, Piperacillin-Tazobactam and Temocillin) are attained in frail patients admitted to the geriatric department.

This monocentric, prospective, observational trial is currently ongoing at the emergency department and geriatric department of the Ghent University Hospital.

Amoxicillin/clavulanic acid 1000/200mg of piperacillin-tazobactam 4000mg or temocillin 2000mg was infused intravenously over 30 minutes using a syringe pump. The standard dosing regimes were used.

An infusion catheter of minimum 18-gauge was placed in the contralateral arm to the arm in which the antibiotic dose was administered. Blood samples were collected from this catheter at first dose and assumed steady state conditions. Steady state was assumed to be reached after minimal 24h (\> 4 doses at four - six hourly interval) of therapy. The goal was to obtain 5 first dose and 5 steady dose samples in every patient.

Material for bacteriological analysis, such as blood cultures, urine samples, sputum, were collected in every patient according to standard care. In case of bacterial growth, MIC's were measured on the reported strains when possible.

Amoxicillin, clavulanic acid, piperacillin, tazobactam and temocillin were measured using a validated ultra-performance liquid chromatographic method with tandem mass spectrometric detection.

Serum creatinine, cystatin C, procalcitonin, infection parameters (CRP, WBC count) and albumin were obtained from standard blood samples performed in these patients at day one and also later on during their therapy.

Three frailty score systems (KATZ, Geriatric 8 - G8, Cumulative Illness Rating Scale - CIRS) were calculated.

Conditions

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Elderly Infection Frailty Frail Elderly Syndrome Infection, Bacterial

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Amoxicillin-clavulanate

Administration of amoxicillin-clavulanate as standard care therapy (4x or 6x 1g/d). Blood sampling in early and steady state dose (up to 5 samplings per dose). Collection of hemocultures, urine samples and sputum samples when possible.

Blood sampling

Intervention Type DIAGNOSTIC_TEST

At predefined time points through a venous catheter already in place. Max. volume to be withdrawn: Maximum 4ml/sample. Maximum 10 samples/patient.

A last blood sample will be taken, if necessary, after the end of antibiotic therapy, between day 7 and day 14. Though blood results preferably will be used from available data from tests already done during standard treatment.

Samples are collected in lithium-heparin tubes (without gel) and centrifuged immediately (within a maximum of 30 minutes after sampling) at room temperature: 8 minutes at 1885g.

Plasma is then collected and divided in two separated labelled Eppendorf tubes 1.5 ml and immediately frozen at - 80 °C. If this is not immediately possible, tubes are frozen at - 20 °C and at regular time points transferred to a freezer at - 80 °C (minimum twice a day).

Sputum sample

Intervention Type DIAGNOSTIC_TEST

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Hemoculture

Intervention Type DIAGNOSTIC_TEST

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Urine sample

Intervention Type DIAGNOSTIC_TEST

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Piperacillin-tazobactam

Administration of piperacillin-tazobactam as standard care therapy (4x 4g/d). Blood sampling in early and steady state dose (up to 5 samplings per dose). Collection of hemocultures, urine samples and sputum samples when possible.

Blood sampling

Intervention Type DIAGNOSTIC_TEST

At predefined time points through a venous catheter already in place. Max. volume to be withdrawn: Maximum 4ml/sample. Maximum 10 samples/patient.

A last blood sample will be taken, if necessary, after the end of antibiotic therapy, between day 7 and day 14. Though blood results preferably will be used from available data from tests already done during standard treatment.

Samples are collected in lithium-heparin tubes (without gel) and centrifuged immediately (within a maximum of 30 minutes after sampling) at room temperature: 8 minutes at 1885g.

Plasma is then collected and divided in two separated labelled Eppendorf tubes 1.5 ml and immediately frozen at - 80 °C. If this is not immediately possible, tubes are frozen at - 20 °C and at regular time points transferred to a freezer at - 80 °C (minimum twice a day).

Sputum sample

Intervention Type DIAGNOSTIC_TEST

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Hemoculture

Intervention Type DIAGNOSTIC_TEST

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Urine sample

Intervention Type DIAGNOSTIC_TEST

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Temocillin

Administration of temocillin as standard care therapy (2x or 3x 2g/d). Blood sampling in early and steady state dose (up to 5 samplings per dose). Collection of hemocultures, urine samples and sputum samples when possible.

Blood sampling

Intervention Type DIAGNOSTIC_TEST

At predefined time points through a venous catheter already in place. Max. volume to be withdrawn: Maximum 4ml/sample. Maximum 10 samples/patient.

A last blood sample will be taken, if necessary, after the end of antibiotic therapy, between day 7 and day 14. Though blood results preferably will be used from available data from tests already done during standard treatment.

Samples are collected in lithium-heparin tubes (without gel) and centrifuged immediately (within a maximum of 30 minutes after sampling) at room temperature: 8 minutes at 1885g.

Plasma is then collected and divided in two separated labelled Eppendorf tubes 1.5 ml and immediately frozen at - 80 °C. If this is not immediately possible, tubes are frozen at - 20 °C and at regular time points transferred to a freezer at - 80 °C (minimum twice a day).

Sputum sample

Intervention Type DIAGNOSTIC_TEST

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Hemoculture

Intervention Type DIAGNOSTIC_TEST

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Urine sample

Intervention Type DIAGNOSTIC_TEST

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Interventions

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Blood sampling

At predefined time points through a venous catheter already in place. Max. volume to be withdrawn: Maximum 4ml/sample. Maximum 10 samples/patient.

A last blood sample will be taken, if necessary, after the end of antibiotic therapy, between day 7 and day 14. Though blood results preferably will be used from available data from tests already done during standard treatment.

Samples are collected in lithium-heparin tubes (without gel) and centrifuged immediately (within a maximum of 30 minutes after sampling) at room temperature: 8 minutes at 1885g.

Plasma is then collected and divided in two separated labelled Eppendorf tubes 1.5 ml and immediately frozen at - 80 °C. If this is not immediately possible, tubes are frozen at - 20 °C and at regular time points transferred to a freezer at - 80 °C (minimum twice a day).

Intervention Type DIAGNOSTIC_TEST

Sputum sample

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Intervention Type DIAGNOSTIC_TEST

Hemoculture

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Intervention Type DIAGNOSTIC_TEST

Urine sample

Bacteriological specimen, such as blood cultures, urine samples, sputum ea., which are usually collected in every patient according to standard care will be retained. If there is bacterial growth, MIC's will be calculated on these strains for study purpose.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Patients presenting at the emergency department and later on admitted to the geriatric department
* Patient age 75 years or older
* Patients with geriatric profile according to KATZ scale, G8 screening test or CIRS score.
* Patient receiving antibiotic treatment (amoxicillin-clavulanate, piperacillin-tazobactam)
* Intravenous access available for blood sampling. For measurement of the peak concentration an intravenous access other than the drug infusion line is required.

Exclusion Criteria

* Admission to other units than the geriatric department incl. the ICU.
* Absence of informed consent
* Known hypersensitivity to beta-lactam antibiotics
* Patients who received oral amoxicillin-clavulanate prior to admission will not be included in the iv. amoxicillin-clavulanate group.
Minimum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Ghent

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tania Desmet, Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

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University Hospital Ghent

Ghent, , Belgium

Site Status RECRUITING

Countries

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Belgium

Central Contacts

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Peter De Paepe, Prof. Dr.

Role: CONTACT

003293325211

Tania Desmet, Dr.

Role: CONTACT

003293321559

Facility Contacts

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Peter De Paepe, Prof. Dr.

Role: primary

003293325211

Tania Desmet, Dr.

Role: backup

003293321559

Other Identifiers

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EC/2017/1369 (BC-01030)

Identifier Type: -

Identifier Source: org_study_id

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