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

Subarachnoid Hemorrhage Clinical Trial

— TANDEM  

Official title:

Prospective Study Evaluating Plasma Exposure of Optimized Antibiotic Therapy According to TDM in Patients With Subarachnoid Haemorrhage (ES) and Cerebral Haemorrhage (EC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04132115
• Other study ID #: CEUR-2019-Os-162
• Status: Recruiting
• Start date: October 1, 2019
• Est. completion date: October 2021

Study information

• Verified date: July 2021
• Source: Azienda Sanitaria-Universitaria Integrata di Udine
• Contact: TIZIANA BOVE, MD, AP
• Phone: +390432555501
• Email: TIZIANA.BOVE[@]UNIUD.IT
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: October 2021
• Est. primary completion date: October 2021
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage
• Subarachnoid Hemorrhage
• Therapeutic Drug Monitoring

Intervention

Drug:
• Piperacillin/tazobactam
Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration
• Meropenem
Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration
• Daptomycin
Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration
• Ceftobiprole
Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration
• Linezolid
Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration
• Vancomycin
Therapeutic drug monitoring(TDM) of this antibiotic plasma concentration
• Fluconazol
Therapeutic drug monitoring (TDM) of this antifungal plasma concentration
• Acyclovir
Therapeutic drug monitoring (TDM) of this antiviral plasma concentration
• Gentamicins
Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration
• Amikacin
Therapeutic drug monitoring (TDM) of this antibiotic plasma concentration
• Ganciclovir
Therapeutic drug monitoring (TDM) of this antiviral plasma concentration

Locations

Country	Name	City	State
Italy	Anesthesiology and Intensive Care Clinic - Department of Medicine - ASUIUD	Udine
Italy	Terapia Intensiva 1	Udine

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Sanitaria-Universitaria Integrata di Udine

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Underexposure to antimicrobial therapy	Prospective evaluation of the proportion of plasma underexposure to hydrophilic antimicrobials due to ARC in patients with subarachnoid haemorrhage (ES) and / or cerebral haemorrhage (EC).	2 years from the date of approval
Secondary	T > MIC	Evaluation of the achievement of the pharmacokinetic / pharmacodynamic target of therapeutic efficacy through the calculation of the parameter T > MIC	2 years from the date of approval
Secondary	AUC / MIC	Evaluation of the achievement of the pharmacokinetic / pharmacodynamic target of therapeutic efficacy through the calculation of the parameter AUC / MIC	2 years from the date of approval
Secondary	Performance of ClCr estimation formulas	Evaluation of the performance of the common CrCl estimation formulas compared to the CrCl measured in the estimation of the systemic clearance of the drugs being studied	2 years from the date of approval