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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Matthieu Pichelin
- メール：matthieu.pichelin@ildys.org
研究連絡先のバックアップ
- 名前：Marion Buyse, PharmD, PhD
- 電話番号：+33298293447
- メール：marion.buyse@ildys.org
研究場所
-
-
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Roscoff、フランス、29680
- 募集
- Fondation Ildys
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コンタクト：
- Marion Buyse, PharmD; PhD
- 電話番号：0298293447
- メール：marion.buyse@ildys.org
-
-
参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
|
Patients with cystic fibrosis treated with ETI receiving antibiotic therapy
Patients with cystic fibrosis treated with ETI receiving antibiotic therapy for pulmonary exacerbation
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Routine antibiotic therapy and therapeutic drug monitoring are performed according to standard clinical practice
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Pharmacokinetic profiles of antibiotics during pulmonary exacerbation treatment
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Clinical efficacy: body weight evolution
時間枠：Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
the Clinical parameters body weight in kilograms
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Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
|
Clinical efficacy: temperature evolution
時間枠：Baseline, Day 3, Day 7-10, and end of antibiotic treatment
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the Clinical parameters temperature in celsius degree
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Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
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Clinical efficacy: appetite evolution
時間枠：Baseline, Day 3, Day 7-10, and end of antibiotic treatment
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the Clinical parameters "appetite" will be score on a scale from 0 to 10 with higher score mean worse outcome
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Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
|
Clinical efficacy: fatigue evolution
時間枠：Baseline, Day 3, Day 7-10, and end of antibiotic treatment
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the Clinical parameters "fatigue" will be score on a scale from 0 to 10 with higher score mean worse outcome
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Baseline, Day 3, Day 7-10, and end of antibiotic treatment
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Clinical efficacy: dyspnea evolution
時間枠：Baseline, Day 3, Day 7-10, and end of antibiotic treatment
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the Clinical parameters "dyspnea" will be score on a scale from 0 to 10 with higher score mean worse outcome
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Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
|
Clinical efficacy: sputum volume
時間枠：Baseline, Day 3, Day 7-10, and end of antibiotic treatment
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the Clinical parameters "sputum volume" will be score on a scale from 0 to 10 with higher score mean worse outcome
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Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
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Clinical efficacy: sputum purulence
時間枠：Baseline, Day 3, Day 7-10, and end of antibiotic treatment
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the Clinical parameters "sputum purulence" will be score on a scale from 0 to 10 with higher score mean worse outcome
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Baseline, Day 3, Day 7-10, and end of antibiotic treatment
|
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biological evolution: Renal function evolution
時間枠：Baseline, Day 3, and end of antibiotic treatment
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renal function will be evaluated by measuring plasma creatinine and calculated glomerular filtration rate
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Baseline, Day 3, and end of antibiotic treatment
|
|
biological evolution: inflammatory markers
時間枠：Baseline, Day 3, and end of antibiotic treatment
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inflammation will be evaluated by measuring plasma c protein reactive and plasma leukocytes concentration
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Baseline, Day 3, and end of antibiotic treatment
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Treatment adherence
時間枠：through study completion, an average 14 days
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Treatment adherence will be evaluated by the ratio of antibiotic doses administered to doses prescribed
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through study completion, an average 14 days
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number of participants with treatment-related adverse events
時間枠：through study completion, an average 14 days
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Adverse events related to antibiotic therapy will be collected and graded according to NCI CTCAE version 6.0
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through study completion, an average 14 days
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協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- RI2025-016
- 2025-A02333-46 (その他の識別子：IDRCB Number)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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