A new multicenter, open-label study is set to determine the pharmacokinetics and tolerability of the novel combination antibiotic, imipenem/cilastatin/relebactam, to treat acute pulmonary exacerbations in patients with cystic fibrosis (CF).
The trial is expected to start in December 2022 and has not yet begun recruiting patients.
The interventional study will enroll 16 adolescent and adult patients hospitalized with an acute pulmonary exacerbation who will receive mipenem/cilastatin/relebactam therapy every 6 hours for 10 to 14 days, with or without standard of care therapy (minoglycoside or fluoroquinolone). At steady state, investigators will collect blood samples for pharmacokinetic studies.
Clearance and volume of distribution of imipenem and relebactam are primary outcome measures, whereas probability of target attainment at 2 mg/L is a secondary outcome measure. Pulmonary function will be assessed as an exploratory clinical endpoint 2 weeks after therapy ends. Moreover, safety and tolerability will be assessed throughout the entire study.
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To be considered for the study, participants must have a documented diagnosis of CF and a sweat chloride greater than 60 mEq/L or a genotype showing 2 well-characterized disease-causing mutations. Moreover, they have to be hospitalized with an acute pulmonary exacerbation documented or suspected to be caused by Pseudomonas aeruginosa.
The study excludes pregnant or breastfeeding females, as well as those patients with a history of moderate or severe hypersensitivity or allergic reaction to any β-lactam agent, certain known or suspected infections at the time of enrollment, renal dysfunction, acute liver injury, or any rapidly progressing disease, immediately life-threatening illness, or other condition or circumstance that would compromise the safety of the patient or the quality of the study data.
Limitations are also applied to patients receiving or intending to receive any other intravenous antibiotic therapy (with few exceptions), inhaled antibiotics, organic anion transporter (OAT) 1 or OAT3 inhibitors, or mipenem or valproic acid. Patients unlikely to remain hospitalized for at least 4 days or those unable to perform pulmonary function tests at baseline or 2 weeks after the end of therapy are also excluded.
The trial is sponsored by Hartford Hospital in Connecticut and includes the participation of 7 other hospitals in the US.
Imipenem/cilastatin/relebactam pharmacokinetics, safety, and outcomes in adults and adolescents with cystic fibrosis. ClinicalTrials.gov. September 30, 2022. Updated September 30, 2022. Accessed October 24, 2022.