Phase 1
Completed N=9
Imipenem-Relebactam Pharmacokinetics in Augmented Renal Clearance
Source: ClinicalTrials.gov NCT04147221 ↗Enrolled (actual)
9
Serious AEs
0.0%
Results posted
Aug 2024
Primary outcomePrimary: Imipenem Clearance — 17.31 L/h
Summary
Critically ill patients with sepsis undergo several physiological alterations that can alter the distribution, metabolism, and elimination of drugs. Some patients with sepsis may realize enhanced cardiac output leading to increases in glomerular filtration that result in increasing drug clearance. This clinical state is referred as Augmented Renal Clearance (ARC). Importantly, many beta-lactam antibiotics can be adversely affected by ARC, and some of these agents required increasing dosage to compensate for enhanced clearance. Imipenem-relebactam is a new broad spectrum antibiotic. This study is designed to assess the pharmacokinetics of both components, imipenem and relebactam, in critically ill patients with ARC.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Imipenem Clearance |
17.31 | — |
| PRIMARY Relebactam Clearance |
11.51 | — |
| SECONDARY Imipenem Area Under the Curve (AUC) |
32.33 | — |
| SECONDARY Relebactam Area Under the Curve (AUC) |
25.54 | — |
Eligibility Criteria
Inclusion Criteria
- APACHE II score > 12 and ≤ 35;
- Creatinine clearance (CrCL) ≥150 mL/min (as calculated by the Cockcroft-Gault equation using ideal or adjusted body weight) within 24 hours of dosing;
- Documented infection or presumed infection as confirmed by the presence of at least one of the following criteria within the past 72 hours:
- Documented fever (oral, rectal, tympanic, or core temperature > 38.5° C)
- Hypothermia (oral, rectal, tympanic, or core temperature 10,000 U/L;
- Any serum creatinine (SCr) before dosing that is increased ≥ 0.3 mg/dL from the baseline SCr used qualifying for enrollment;
- Urinary output 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;
- Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator);
- Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of study data;
- Planned or prior participation in any other interventional drug study within 30 days.
Data sourced from ClinicalTrials.gov (NCT04147221). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.