Clinical trial NCT05373615: Cefiderocol Plasma Concentrations in Patients Receiving Renal Replacement Therapy
Official title: Effect of Continuous Renal Replacement Therapy and Residual Renal Clearance on Cefiderocol Pharmacokinetics in Critically Ill Adult Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Lead sponsor: Hartford Hospital
Sponsor class: OTHER
Collaborators: name: Shionogi Inc.
First posted: 2022-05-13
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Continuous renal replacement therapies (CRRT) such as continuous venovenous hemofiltration are used to provide renal support for critically ill patients with acute kidney injury (AKI), particularly patients who are hemodynamically unstable. It is well known that critically ill patients may experience alterations in antibiotic pharmacokinetics, and as a result, dosing modifications are generally required. There is a need to understand how CRRT affect the pharmacokinetics and disposition of drugs. This study is designed to assess the pharmacokinetics of the new broad-spectrum antibiotic, Cefiderocol, in critically ill patient receiving CRRT.

Detailed description: This is a prospective, multi-center, open-label, Phase 1b, pharmacokinetic study of Cefiderocol in 16 critically ill patients receiving CRRT support. Informed consent will be collected from all study participants, legal authorized representative, or their next of kin in order to participate. This is not a treatment study; all participants will receive standard of care antibiotics which may include cefiderocol as necessary to treat any current infection.

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or older;
2. Receiving CRRT including CVVH, CVVHD, and CVVHDF support.

Exclusion Criteria:

1. Females who are pregnant or breast-feeding;
2. History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic (a history of mild rash to a cephalosporin followed by uneventful re-exposure is not a contraindication);
3. A hemoglobin less than 8 gm/dl at baseline;
4. Acute liver injury, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 times the upper limit of normal, or AST or ALT \> 3 times the upper limit of normal with an associated total bilirubin \> 2 times upper limit of normal;
5. Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator);
6. Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of study data.

Primary outcomes:
measure: Cefiderocol concentration
timeFrame: 8 to 12 hours
measure: Cefiderocol clearance
timeFrame: 8 to 12 hours
measure: Cefiderocol maximum concentration
timeFrame: 8 to 12 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
Study officials:
References: