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Pharmacokinetics of Antibiotics in Patients With Cystic Fibrosis Trated With Elexacaftor/Tezacaftor/Ivacaftor (ETI) (PKCF)

1 juni 2026 bijgewerkt door: Fondation Ildys

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Observationeel

Inschrijving (Geschat)

30

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Kind
  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Bemonsteringsmethode

Niet-waarschijnlijkheidssteekproef

Studie Bevolking

CF patients

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Cohorten en interventies

Groep / Cohort
Interventie / Behandeling
Patients with cystic fibrosis treated with ETI receiving antibiotic therapy
Patients with cystic fibrosis treated with ETI receiving antibiotic therapy for pulmonary exacerbation
Ander: No intervention assigned
Routine antibiotic therapy and therapeutic drug monitoring are performed according to standard clinical practice

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Pharmacokinetic profiles of antibiotics during pulmonary exacerbation treatment
Tijdsspanne: 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.
Day 3 of antibiotic therapy

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Clinical efficacy: body weight evolution
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Fondation Ildys

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

19 maart 2026

Primaire voltooiing (Geschat)

1 maart 2028

Studie voltooiing (Geschat)

1 mei 2028

Studieregistratiedata

Eerst ingediend

15 mei 2026

Eerst ingediend dat voldeed aan de QC-criteria

1 juni 2026

Eerst geplaatst (Werkelijk)

5 juni 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

5 juni 2026

Laatste update ingediend die voldeed aan QC-criteria

1 juni 2026

Laatst geverifieerd

1 juni 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • RI2025-016
  • 2025-A02333-46 (Andere identificatie: IDRCB Number)

Plan Individuele Deelnemersgegevens (IPD)

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ONBESLIST

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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