Optimized Antibiotic Therapy in Patients With Subarachnoid Haemorrhage (ES) and Cerebral Haemorrhage (EC)

NCT ID: NCT04132115

Last Updated: 2021-07-21

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 104 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-10-01
• Study Completion Date: 2021-10-31

Brief Summary

A recent prospective observational clinical study conducted in an intensive care unit of a third level US university hospital showed that 94% of patients with ES and 50% of those with EC had an ARC for a duration of at least one day during the hospital stay.

Although there is currently a great deal of evidence describing ARC in various subgroups of critically ill patients, on the other hand there is little documentation regarding the effect that ARC can have on exposure to renally eliminated drugs.

Therefore, the aim of this study is to prospectively evaluate the proportion of plasma under-exposure to hydrophilic antimicrobials in patients with ES or EC and with ARC, in order to verify whether the recommended dosage regimens for these drugs are adequate for reaching the pharmacodynamic targets of therapeutic efficacy.

Detailed Description

Haemorrhagic stroke is a devastating disease with a high rate of disability and mortality. In addition to the direct effects of the haemorrhagic event and to the secondary neurological complications, patients with haemorrhagic strokes are predisposed to medical complications that can have a direct impact on both clinical outcome and treatment costs. It has been estimated that between 79% and 100% of patients with subarachnoid haemorrhage (ES) and cerebral haemorrhage (EC) have at least one of these complications. Among them, the most common are infections, seizures, hyponatremia, hypomagnesemia, hypokalemia and venous thromboembolism.

A possible reason that can be responsible for such a high frequency of complications, especially infectious, can be identified in a pathophysiological alteration of the circulatory and renal haemodynamics of this population. Specifically, these patients frequently have a hyperdynamic state which results in a high renal clearance (CrCl) (augmented renal clearance - ARC, defined as a measured CrCl ≥ 130 ml/min/1.73m2). In this regard, a recent prospective observational clinical study conducted in an intensive care unit of a third level US university hospital showed that 94% of patients with ES and 50% of those with EC had an ARC for a duration of at least one day during the hospital stay.

In consideration of the fact that the ARC has been historically underestimated and that an accurate assessment of renal function through the measured CrCl is not regularly carried out on all patients even if they are critical, the main risk from the point of view of therapeutic appropriateness is that of not adjust the dosing regimen of drugs eliminated through the kidney in relation to the presence and extent of the ARC. Moreover, the clinician often ignores the time course of the ARC as well as the modalities with which to carry out the dosage adjustment. This could lead to sub-therapeutic concentrations for renally excreted drugs, as typically are water-soluble antibiotics such as beta-lactams, aminoglycosides, daptomycin, linezolid, antifungal fluconazole and antivirals ganciclovir and aciclovir, resulting in an increase in the risk of therapeutic failure.

Although there is currently a great deal of evidence describing ARC in various subgroups of critically ill patients, on the other hand there is little documentation regarding the effect that ARC can have on exposure to renally eliminated drugs.

Therefore, the aim of this study is to prospectively evaluate the proportion of plasma under-exposure to hydrophilic antimicrobials in patients with ES or EC and with ARC, in order to verify whether the recommended dosage regimens for these drugs are adequate for reaching the pharmacodynamic targets of therapeutic efficacy.

Conditions

Therapeutic Drug Monitoring; Subarachnoid Hemorrhage; Intracerebral Hemorrhage

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Piperacillin/tazobactam

Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration

Intervention Type: DRUG

Meropenem

Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration

Intervention Type: DRUG

Daptomycin

Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration

Intervention Type: DRUG

Ceftobiprole

Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration

Intervention Type: DRUG

Linezolid

Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration

Intervention Type: DRUG

Vancomycin

Therapeutic drug monitoring(TDM) of this antibiotic plasma concentration

Intervention Type: DRUG

Fluconazol

Therapeutic drug monitoring (TDM) of this antifungal plasma concentration

Intervention Type: DRUG

Acyclovir

Therapeutic drug monitoring (TDM) of this antiviral plasma concentration

Intervention Type: DRUG

Gentamicins

Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration

Intervention Type: DRUG

Amikacin

Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration

Intervention Type: DRUG

Ganciclovir

Therapeutic drug monitoring (TDM) of this antiviral plasma concentration

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients of both sexes > 18 years admitted for ES or EC
• Patients to which one or more water-soluble antibiotics, antifungals or antivirals subject of the present study are prescribed
• Patients who present ARC

Exclusion Criteria

• Patients in whom the plasma samples are contaminated
• Patients in whom the plasma samples are performed in a way that does not comply with the prepared company protocol.
• Patients with BMI < 18 kg / m2.
• Patients with a serum creatinine > 1.4 mg / dL at entry
• Pregnant patients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Sanitaria-Universitaria Integrata di Udine

OTHER

Sponsor Role: lead

Responsible Party

Luigi Vetrugno

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Anesthesiology and Intensive Care Clinic - Department of Medicine - ASUIUD

Udine, , Italy

Site Status: RECRUITING

Terapia Intensiva 1

Udine, , Italy

Site Status: NOT_YET_RECRUITING

Countries

Italy

Central Contacts

TIZIANA BOVE, MD, AP

Role: CONTACT

TIZIANA.BOVE@UNIUD.IT

+390432555501

LUIGI VETRUGNO, MD, AP

Role: CONTACT

LUIGI.VETRUGNO@UNIUD.IT

+390432555501

Facility Contacts

Luigi Vetrugno, Doctor

Role: primary

luigi.vetrugno@asuiud.sanita.fvg.it

+393382873386

Tiziana Bove, Professor

Role: backup

tiziana.bove@asuiud.sanita.fvg.it

+393474785763

Cristian Deana, MD

Role: primary

Other Identifiers

CEUR-2019-Os-162

Identifier Type: -

Identifier Source: org_study_id