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

NCT07629986 | Recruiting

• 2 other identifiers: RI2025-0162025-A02333-46
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cystic Fibrosis (CF); Pulmonary Exacerbation; Respiratory Infection Bacterial

Keywords

Cystic Fibrosis; CFTR modulators; Elexacaftor/Tezacaftor/Ivacaftor; Antibiotics; Pharmacokinetics; Therapeutic drug monitoring; Pulmonary Exacerbation

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic profiles of antibiotics during pulmonary exacerbation treatment

  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

Secondary Outcomes (11)

• Clinical efficacy: body weight evolution

  Baseline, Day 3, Day 7-10, and end of antibiotic treatment

• Clinical efficacy: temperature evolution

  Baseline, Day 3, Day 7-10, and end of antibiotic treatment

• Clinical efficacy: appetite evolution

  Baseline, Day 3, Day 7-10, and end of antibiotic treatment

• Clinical efficacy: fatigue evolution

  Baseline, Day 3, Day 7-10, and end of antibiotic treatment

• Clinical efficacy: dyspnea evolution

  Baseline, Day 3, Day 7-10, and end of antibiotic treatment

Study Arms (1)

Patients with cystic fibrosis treated with ETI receiving antibiotic therapy

Patients with cystic fibrosis treated with ETI receiving antibiotic therapy for pulmonary exacerbation

Other: No intervention assigned

Interventions

No intervention assigned OTHER

Routine antibiotic therapy and therapeutic drug monitoring are performed according to standard clinical practice

Patients with cystic fibrosis treated with ETI receiving antibiotic therapy

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

CF patients

You may qualify if:

• 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

You may not qualify if:

• Lung transplantation or heart-lung transplantation
• Patients under guardianship or curatorship
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Fondation Ildys: lead

Study Sites (1)

Fondation ILDYS

Roscoff, 29680, France

RECRUITING

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Central Study Contacts

Marion Buyse, PharmD, PhD

CONTACT

+33298293447; marion.buyse@ildys.org

Matthieu Pichelin

CONTACT

matthieu.pichelin@ildys.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2026
• First Posted: June 5, 2026
• Study Start: March 19, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: June 5, 2026

Record last verified: 2026-06

Locations

FR (1)