Pharmacokinetics of Antibiotics in Patients With Cystic Fibrosis Trated With Elexacaftor/Tezacaftor/Ivacaftor (ETI) (PKCF)
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.
Studienübersicht
Status
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Geschätzt)
Kontakte und Standorte
Studienkontakt
- Name: Matthieu Pichelin
- E-Mail: matthieu.pichelin@ildys.org
Studieren Sie die Kontaktsicherung
- Name: Marion Buyse, PharmD, PhD
- Telefonnummer: +33298293447
- E-Mail: marion.buyse@ildys.org
Studienorte
-
-
-
Roscoff, Frankreich, 29680
- Rekrutierung
- Fondation Ildys
-
Kontakt:
- Marion Buyse, PharmD; PhD
- Telefonnummer: 0298293447
- E-Mail: marion.buyse@ildys.org
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Kind
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Probenahmeverfahren
Studienpopulation
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
Kohorten und Interventionen
Gruppe / Kohorte |
Intervention / Behandlung |
|---|---|
|
Patients with cystic fibrosis treated with ETI receiving antibiotic therapy
Patients with cystic fibrosis treated with ETI receiving antibiotic therapy for pulmonary exacerbation
|
Routine antibiotic therapy and therapeutic drug monitoring are performed according to standard clinical practice
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Pharmacokinetic profiles of antibiotics during pulmonary exacerbation treatment
Zeitfenster: Day 3 of antibiotic therapy
|
Plasma antibiotic concentrations will be measured at Day 3 of treatment to determine pharmacokinetic parameters including:
Pharmacokinetic/pharmacodynamic ratios will be evaluated according to bacterial minimum inhibitory concentrations (MICs):
|
Day 3 of antibiotic therapy
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Clinical efficacy: body weight evolution
Zeitfenster: Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
the Clinical parameters body weight in kilograms
|
Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
|
Clinical efficacy: temperature evolution
Zeitfenster: Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
the Clinical parameters temperature in celsius degree
|
Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
|
Clinical efficacy: appetite evolution
Zeitfenster: 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
|
Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
|
Clinical efficacy: fatigue evolution
Zeitfenster: 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
|
Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
|
Clinical efficacy: dyspnea evolution
Zeitfenster: 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
|
Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
|
Clinical efficacy: sputum volume
Zeitfenster: 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
|
Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
|
Clinical efficacy: sputum purulence
Zeitfenster: 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
|
Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
|
biological evolution: Renal function evolution
Zeitfenster: Baseline, Day 3, and end of antibiotic treatment
|
renal function will be evaluated by measuring plasma creatinine and calculated glomerular filtration rate
|
Baseline, Day 3, and end of antibiotic treatment
|
|
biological evolution: inflammatory markers
Zeitfenster: Baseline, Day 3, and end of antibiotic treatment
|
inflammation will be evaluated by measuring plasma c protein reactive and plasma leukocytes concentration
|
Baseline, Day 3, and end of antibiotic treatment
|
|
Treatment adherence
Zeitfenster: through study completion, an average 14 days
|
Treatment adherence will be evaluated by the ratio of antibiotic doses administered to doses prescribed
|
through study completion, an average 14 days
|
|
number of participants with treatment-related adverse events
Zeitfenster: 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
|
through study completion, an average 14 days
|
Mitarbeiter und Ermittler
Sponsor
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- RI2025-016
- 2025-A02333-46 (Andere Kennung: IDRCB Number)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .