Pharmacokinetics of Antibiotics in Patients With Cystic Fibrosis Trated With Elexacaftor/Tezacaftor/Ivacaftor (ETI)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: No intervention assigned.
- Who it may be relevant to
- Registry conditions: Cystic Fibrosis (CF), Pulmonary Exacerbation, Respiratory Infection Bacterial. Basic parameters: from 12 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
Cystic fibrosis (CF) is associated with major pharmacokinetic and pharmacodynamic alterations affecting antibiotic exposure, including changes in absorption, distribution, metabolism, and elimination. Historically, these alterations justified the use of higher antibiotic doses in CF patients in order to achieve therapeutic concentrations and improve pulmonary outcomes. The advent of highly effective CFTR modulators, particularly the triple combination elexacaftor/tezacaftor/ivacaftor (ETI), has substantially improved pulmonary function, nutritional status, inflammatory burden, and quality of life in patients with CF. ETI therapy also appears to modify respiratory microbiology and reduce the frequency of pulmonary exacerbations. These clinical and physiological improvements may alter antibiotic pharmacokinetics and pharmacodynamics in patients with CF, potentially making current high-dose antibiotic recommendations less appropriate for some patients. Since repeated exposure to high-dose antibiotics is associated with cumulative toxicities, particularly aminoglycoside-related ototoxicity and nephrotoxicity, reassessment of antibiotic dosing strategies is warranted. The PKCF study is a multicenter, prospective, observational, non-interventional study designed to characterize the pharmacokinetic profiles of intravenous antibiotics administered during pulmonary exacerbations in adolescents and adults with cystic fibrosis receiving ETI therapy.
Detailed description
Patients with cystic fibrosis experience substantial physiological changes that affect the pharmacokinetics of medications, including antibiotics. Altered gastrointestinal absorption, increased volume of distribution, enhanced renal clearance, chronic systemic inflammation, and modified protein binding have historically led to recommendations for increased antibiotic dosing in CF patients.
Additionally, thick airway mucus, biofilm formation, high bacterial inoculum, and chronic airway infection contribute to altered antibiotic pharmacodynamics and reduced antibiotic efficacy.
Highly effective CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI), have profoundly changed the clinical course of cystic fibrosis by improving lung function, reducing pulmonary exacerbations, improving nutritional status, and modifying airway microbiology. These changes may normalize or partially normalize antibiotic pharmacokinetics and pharmacodynamics.
However, evidence regarding the impact of ETI therapy on antibiotic pharmacokinetics remains extremely limited. To date, only one retrospective pediatric study has evaluated the effect of CFTR modulators on intravenous tobramycin pharmacokinetics during pulmonary exacerbations.
The PKCF study aims to prospectively evaluate plasma antibiotic concentrations and pharmacokinetic parameters in CF patients receiving ETI during pulmonary exacerbations requiring antibiotic therapy. Antibiotic concentrations will be compared with established PK/PD targets according to current national recommendations.
The study may contribute to future optimization of antibiotic dosing strategies in patients with CF treated with ETI, while minimizing toxicity and supporting antimicrobial stewardship.
Interventions
- Other No intervention assigned
Routine antibiotic therapy and therapeutic drug monitoring are performed according to standard clinical practice
Primary outcome measures
- Pharmacokinetic profiles of antibiotics during pulmonary exacerbation treatment [Time frame: Day 3 of antibiotic therapy]
Secondary outcome measures (11)
- Clinical efficacy: body weight evolution [Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
- Clinical efficacy: temperature evolution [Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
- Clinical efficacy: appetite evolution [Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
- Clinical efficacy: fatigue evolution [Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
- Clinical efficacy: dyspnea evolution [Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
- Clinical efficacy: sputum volume [Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
- Clinical efficacy: sputum purulence [Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
- biological evolution: Renal function evolution [Time frame: Baseline, Day 3, and end of antibiotic treatment]
- biological evolution: inflammatory markers [Time frame: Baseline, Day 3, and end of antibiotic treatment]
- Treatment adherence [Time frame: through study completion, an average 14 days]
- number of participants with treatment-related adverse events [Time frame: through study completion, an average 14 days]
Eligibility criteria
Inclusion criteria
- Diagnosis of cystic fibrosis confirmed by sweat test and/or genetic testing
- Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for at least 3 months
- Age 12 years or older
- Patient informed and not objecting to participation; for minors, parents/legal guardians informed and not objecting to participation
- Clinical indication for antibiotic therapy for pulmonary exacerbation or respiratory infection according to treating physician
- Affiliation to a social security system
Exclusion criteria
- Lung transplantation or heart-lung transplantation
- Patients under guardianship or curatorship
- Pregnant or breastfeeding women
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
France · 1 center
- Fondation ILDYS — Roscoff
Identifiers
NCT: NCT07629986 · RI2025-016 · 2025-A02333-46