Fondation ILDYS
Roscoff, 29680, France
Location status: Recruiting
Recruiting
NCT Number: NCT07629986
Pharmacokinetics of Antibiotics in Patients With Cystic Fibrosis Trated With Elexacaftor/Tezacaftor/Ivacaftor (ETI)
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.
Recruiting
Interested in participating?
Request InfoKey information
Conditions
Age range
12 year and older
Sex eligibility
All sexes
Study type
Observational
Primary location
About this study
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.
Who can participate
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
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
Treatment and study plan
No intervention assigned
OtherRoutine antibiotic therapy and therapeutic drug monitoring are performed according to standard clinical practice
Primary outcomes
-
Pharmacokinetic profiles of antibiotics during pulmonary exacerbation treatment
Time frame: Day 3 of antibiotic therapy
Plasma antibiotic concentrations will be measured at Day 3 of treatment to determine pharmacokinetic parameters including:
- Cmax (maximum plasma concentration)
- Cmin (minimum plasma concentration)
Pharmacokinetic/pharmacodynamic ratios will be evaluated according to bacterial minimum inhibitory concentrations (MICs):
- Cmin/MIC ratio for time-dependent antibiotics
- Cmax/MIC ratio for concentration-dependent antibiotics Antibiotic exposure will be compared with PK/PD targets validated by national expert recommendations.
Secondary outcomes
-
Clinical efficacy: body weight evolution
Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment
the Clinical parameters body weight in kilograms
-
Clinical efficacy: temperature evolution
Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment
the Clinical parameters temperature in celsius degree
-
Clinical efficacy: appetite evolution
Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment
the Clinical parameters "appetite" will be score on a scale from 0 to 10 with higher score mean worse outcome
-
Clinical efficacy: fatigue evolution
Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment
the Clinical parameters "fatigue" will be score on a scale from 0 to 10 with higher score mean worse outcome
-
Clinical efficacy: dyspnea evolution
Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment
the Clinical parameters "dyspnea" will be score on a scale from 0 to 10 with higher score mean worse outcome
-
Clinical efficacy: sputum volume
Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment
the Clinical parameters "sputum volume" will be score on a scale from 0 to 10 with higher score mean worse outcome
-
Clinical efficacy: sputum purulence
Time frame: Baseline, Day 3, Day 7-10, and end of antibiotic treatment
the Clinical parameters "sputum purulence" will be score on a scale from 0 to 10 with higher score mean worse outcome
-
biological evolution: Renal function evolution
Time frame: Baseline, Day 3, and end of antibiotic treatment
renal function will be evaluated by measuring plasma creatinine and calculated glomerular filtration rate
-
biological evolution: inflammatory markers
Time frame: Baseline, Day 3, and end of antibiotic treatment
inflammation will be evaluated by measuring plasma c protein reactive and plasma leukocytes concentration
-
Treatment adherence
Time frame: through study completion, an average 14 days
Treatment adherence will be evaluated by the ratio of antibiotic doses administered to doses prescribed
-
number of participants with treatment-related adverse events
Time frame: through study completion, an average 14 days
Adverse events related to antibiotic therapy will be collected and graded according to NCI CTCAE version 6.0
Study contacts
Contact information is provided by the study sponsor or research team.
Marion Buyse, PharmD, PhD
CONTACT
Matthieu Pichelin
CONTACT
Sponsors and collaborators
Lead sponsor
Fondation Ildys
Other
Registry information
Acronym: PKCF
Important dates
- Study start
- 2026
- Primary completion
- 2028
- Study completion
- 2028
- First posted
- Jun 5, 2026
- Registry last updated
- Jun 5, 2026
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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