Идёт набор NCT07629986

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

— Наблюдательное Cystic Fibrosis (CF) Pulmonary Exacerbation Respiratory Infection Bacterial

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: No intervention assigned.
Кому может быть актуально: Состояния в реестре: Cystic Fibrosis (CF), Pulmonary Exacerbation, Respiratory Infection Bacterial. Базовые параметры: от 12 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: Франция
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

Не всё понятно в терминах? Прочитайте наш гид для пациентов →

Обзор

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.

Подробное описание

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.

Вмешательства

Другое No intervention assigned
Routine antibiotic therapy and therapeutic drug monitoring are performed according to standard clinical practice

Первичные конечные точки

Pharmacokinetic profiles of antibiotics during pulmonary exacerbation treatment [Срок оценки: Day 3 of antibiotic therapy]

Вторичные конечные точки (11)

Clinical efficacy: body weight evolution [Срок оценки: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
Clinical efficacy: temperature evolution [Срок оценки: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
Clinical efficacy: appetite evolution [Срок оценки: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
Clinical efficacy: fatigue evolution [Срок оценки: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
Clinical efficacy: dyspnea evolution [Срок оценки: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
Clinical efficacy: sputum volume [Срок оценки: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
Clinical efficacy: sputum purulence [Срок оценки: Baseline, Day 3, Day 7-10, and end of antibiotic treatment]
biological evolution: Renal function evolution [Срок оценки: Baseline, Day 3, and end of antibiotic treatment]
biological evolution: inflammatory markers [Срок оценки: Baseline, Day 3, and end of antibiotic treatment]
Treatment adherence [Срок оценки: through study completion, an average 14 days]
number of participants with treatment-related adverse events [Срок оценки: through study completion, an average 14 days]

Критерии участия

Критерии включения

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