Clinical impact of pharmacokinetic monitoring of antibiotics in critically ill patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Decision date (initial)

2023-07-10

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Hospital de la Santa Creu i Sant Pau

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy

To assess the clinical impact of pharmacokinetic monitoring of antibiotics in the critically ill patient. The following antibiotics are considered in this study: meropenem, cefepime, piperacillin/tazobactam, linezolid and daptomycin.

Secondary objectives 6

1. - Identify patient and infection characteristics of each group.
2. - Analyse whether monitoring involves changes in regimen, dosage or optimisation of administration with respect to the initial dosage.
3. - Describe in which subgroups more differences in dosing and/or clinical changes are observed.
4. - Assess the characteristics of patients requiring a particular type of intervention (increase or optimisation of dosage and decrease in dosage).
5. - Analyse whether there are differences in the occurrence of resistance between control and intervention groups.
6. - Review whether there is a correlation between patients with elevated plasma concentrations and analytical alterations.

Conditions and MedDRA coding

Critical Patients admitted to the ICU

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Patients who are candidates for study entry must meet the following criteria (detailed in sections 5.1 Study Type and Design): - Age ≥ 18 years. - Patients admitted to the Intensive Care Unit (ICU) who start treatment with the antibiotics under study and who meet the criteria for inclusion in the intervention or control group (detailed in sections 5.1 Study design). - Intervention group: initiation of treatment during the 48 hours prior to the plasma concentration determination (day and time set weekly). - Control group: start of treatment from the weekly time at which the plasma concentration of the intervention group is determined, until the same number of patients as the intervention group is reached that same week.

Exclusion criteria 1

1. Patients with a duration of antibiotic treatment < 72 hours, have an ICU stay < 48 hours or do not meet the inclusion criteria are excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - Days of admission to ICU - Days of hospital admission - Days on mechanical ventilation - Days on vasoactive drug treatment - Fever - Biomarkers: procalcitonin and C-reactive protein - SOFA scale. Includes Glasgow scale, oxygen saturation, FIO2, mean arterial pressure, dobutamine use, dopamine dose, noradrenaline dose, daily diuresis (measured on days 1, 3, 7 and end of treatment) - Mortality at 30 days.

Secondary endpoints 6

1. Sociodemographics: age, sex, weight, height, medical service (intensive care, coronary unit, anaesthesia).
2. Initial clinical data: Charlson index, 10-year survival according to Charlson, presence of relevant comorbidities (diabetes mellitus, heart failure, chronic obstructive pulmonary disease, chronic renal failure, active neoplasia, chronic treatment with corticosteroids, immunosuppressants or chemotherapy, solid organ or haematopoietic progenitor transplant recipients, liver cirrhosis), APACHEII, SAPSII, reason for admission.........
3. Treatment data: antibiotic administered (duration of treatment, dosing regimen, dose and time of administration), date and time of antibiotic initiation, antibiotic used previously (only up to the previous day), concomitant anti-infectives used.
4. Other analytical variables (day of start of treatment, day 3 and day 7 of treatment and end of treatment): urea, creatinine, bilirubin, aspartate transaminase (AST) and alanine transaminase (ALT) enzymes, alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), creatinine kinase (CK), albumin, haemoglobin, haematocrit, platelets, leukocytes, neutrophils, activated partial thromboplastin time (aPTT) and volume, collection time and urine creatinine if performed during treatment.
5. Other clinical data during follow-up: positive cultures (sample, microorganism, sensitivity and MIC if tested), Clostridium difficile toxin detection, water balance, ECMO, ventricular assist or renal replacement therapy (RRT) including duration, type and modality and regimen in case of continuous RRT.
6. Intervention data: number of interventions, date and time of intervention, dosing regimen and administration time after intervention, estimated pharmacokinetic parameters (minimum or trough concentration, maximum or peak concentration, area under the 24-hour curve, volume of distribution, half-life).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Sponsor organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Address

Calle De San Quintin 77-79

City

Barcelona

Postcode

08041

Country

Spain

Scientific contact point

Organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Contact name

UICEC

Public contact point

Organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Contact name

UICEC

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

2 submissions — initial application plus substantial / non-substantial modifications