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

1. juni 2026 opdateret af: 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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Observationel

Tilmelding (Anslået)

30

Kontakter og lokationer

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Studiekontakt

Undersøgelse Kontakt Backup

Studiesteder

  • Frankrig
      • Roscoff, Frankrig, 29680
        • Rekruttering
        • Fondation Ildys
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Barn
  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Prøveudtagningsmetode

Ikke-sandsynlighedsprøve

Studiebefolkning

CF patients

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

Kohorter og interventioner

Gruppe / kohorte
Intervention / Behandling
Patients with cystic fibrosis treated with ETI receiving antibiotic therapy
Patients with cystic fibrosis treated with ETI receiving antibiotic therapy for pulmonary exacerbation
Andet: No intervention assigned
Routine antibiotic therapy and therapeutic drug monitoring are performed according to standard clinical practice

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Pharmacokinetic profiles of antibiotics during pulmonary exacerbation treatment
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Clinical efficacy: body weight evolution
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

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Sponsor

Fondation Ildys

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

19. marts 2026

Primær færdiggørelse (Anslået)

1. marts 2028

Studieafslutning (Anslået)

1. maj 2028

Datoer for studieregistrering

Først indsendt

15. maj 2026

Først indsendt, der opfyldte QC-kriterier

1. juni 2026

Først opslået (Faktiske)

5. juni 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

5. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

1. juni 2026

Sidst verificeret

1. juni 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • RI2025-016
  • 2025-A02333-46 (Anden identifikator: IDRCB Number)

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