PREterm Infants With Bronchial Obstruction - Prospective Study of Efficacy and Safety of Inhaled Tiotropium (PRETIO)
A Prospective, Randomized, Controlled, Crossover Phase IV Study to Evaluate the Efficacy and Safety of Inhaled Tiotropium in Preterm Infants With Bronchial Obstruction Compared to Standard Treatment
The purpose of this clinical trial is to evaluate the efficacy and safety of inhaled tiotropium bromide (Spiriva Respimat) in preterm-born children and adolescents suffering from chronic bronchial obstruction.
Preterm infants often experience persistent narrowing of the airways, which leads to shortness of breath, chronic respiratory symptoms, and reduced exercise tolerance.
Tiotropium is a long-acting muscarinic antagonist (LAMA) that helps dilate the airways and facilitate breathing. While this medication is already approved for pediatric patients aged 6 years and older with severe asthma, its efficacy and safety have not yet been validated in the specific population of preterm infants with bronchial obstruction. This study aims to fill this clinical knowledge gap.
This is a non-commercial, monocentric, prospective, randomized, open-label, phase IV study utilizing a 2x2 crossover design. The trial will enroll 50 participants aged 6 to 18 years. Each participant will undergo two distinct 3-month phases: a treatment period with daily inhaled tiotropium (5 µg once daily) and a control observation period without long-term anticholinergic therapy. The sequence of these periods will be randomly assigned to each participant. The primary objective is to demonstrate lung function improvement by evaluating the change in forced expiratory volume in 1 second (FEV1) expressed in liters and Forced Vital Capacity (FVC) expressed in liters between the treatment and control periods. No blood samples or invasive procedures are required for this study.
調査の概要
詳細な説明
This clinical trial is designed as an investigator-initiated, academic, phase IV, randomized, open-label, 2x2 crossover study to evaluate the response to inhaled tiotropium bromide in children and adolescents born prematurely who suffer from chronic bronchial obstruction.
The study consists of two different sequences:
- Sequence A (Treatment first): Participants receive inhaled tiotropium (5 µg once daily via Spiriva Respimat) for 3 months, followed by a 4-week washout period, and subsequently undergo a 3-month control observation period under standard treatment.
- Sequence B (Control first): Participants start with a 3-month control observation period under standard treatment, followed immediately (without a washout period) by a 3-month treatment period with daily inhaled tiotropium.
Clinical and spirometric assessments (including Forced Expiratory Volume in 1 second in liters - FEV₁, Forced Vital Capacity in liters - FVC, Peak Expiratory Flow in liters per second - PEF, Forced Expiratory Flow between 25% and 75% of FVC in liters per second - FEF₂₅-₇₅ parameters) will be performed at baseline, at the crossover point (end of the first period), and at the end of the study (end of the second period). Participants or their parents will maintain daily diaries to log respiratory symptoms, rescue medication - short-acting beta₂-agonist (SABA) use, and potential acute exacerbations throughout the trial.
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究連絡先
- 名前：Martina Racková, Mgr., MBA
- 電話番号：+420 224 963 097
- メール：martina.rackova@vfn.cz
研究連絡先のバックアップ
- 名前：Pavel Michálek, Prof., MUDr.
- 電話番号：+420 224 962 666
- メール：pavel.michalek@vfn.cz
研究場所
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Prague、チェコ、128 08
- General University Hospital in Prague, Department of Paediatrics and Inherited Metabolic Disorders (KPDPM)
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Age between 6 and 18 years.
- History of preterm birth (defined as delivery at < 37 gestational weeks).
- Spirometrically proven bronchial obstruction, defined as a z-score of FEV1 and/or >= 2 other parameters - Forced Vital Capacity (FVC; liters [L]), Peak Expiratory Flow (PEF; liters per second [L/s]), and Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity (FEF25-75; liters per second [L/s]).) below -1.65 SD.
- Positive bronchodilatation test, defined as an increase in FEV₁ or FVC of more than 10% of the corresponding GLI-predicted value following administration of ipratropium bromide. Bronchodilator responsiveness will be calculated separately for FEV₁ and FVC as:
[(post-bronchodilator value - pre-bronchodilator value) / predicted value] × 100.
FEV₁ and FVC will be measured in litres (L) after ipratropium administration.
- Acceptable spirometry performance in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) 2019 standards.
- No long-term inhalation therapy (such as a long-acting beta₂-agonist (LABA) or a combination of an inhaled corticosteroid and a long-acting beta₂-agonist (ICS/LABA)) within the last month prior to study enrollment.
Exclusion Criteria:
- Other chronic respiratory diseases (e.g., asthma, cystic fibrosis).
- Anatomical abnormalities of the respiratory tract or presence of glaucoma.
- Congenital malformations of the uropoetic tract or cardiac arrhythmias/congenital heart defects.
- Concomitant use of anticholinergic medications for enuresis nocturna.
- Pregnancy (mandatory urine screening required for all female participants aged 13 years and older).
- Insufficient cooperation or inability to properly perform spirometry maneuvers.
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
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：クロスオーバー割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Sequence A: Tiotropium first
Participants in this sequence receive inhaled tiotropium bromide (5 µg once daily via Spiriva Respimat) for 3 months, followed by a 4-week washout period, and then undergo a 3-month control observation period with standard treatment.
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Inhaled tiotropium bromide administered via Spiriva Respimat inhaler.
Dose: 5 µg (2 actuations of 2.5 µg) once daily for a total duration of 12 weeks.
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実験的：Sequence B: Control first
Participants in this sequence begin with a 3-month control observation period under standard treatment (no long-term anticholinergic therapy), immediately followed by a 3-month treatment period with daily inhaled tiotropium (5 µg once daily).
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Inhaled tiotropium bromide administered via Spiriva Respimat inhaler.
Dose: 5 µg (2 actuations of 2.5 µg) once daily for a total duration of 12 weeks.
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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 |
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Absolute change from Baseline in Forced Expiratory Volume in 1 Second (FEV1) expressed in liters (L)
時間枠：At the end of the 3-month treatment period and at the end of the 3-month control period (specifically at Week 12 and Week 28 for Sequence A, or at Week 12 and Week 24 for Sequence B)
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The outcome will be the within-participant difference in forced expiratory volume in 1 second (FEV₁), expressed in litres (L) and Forced Vital Capacity in liters - FVC, between the end of the 3-month tiotropium treatment period and the end of the 3-month control observation period. FEV₁ and FVC will also be expressed as a z-score and percentage of the predicted value calculated using the applicable Global Lung Function Initiative (GLI) reference equations. The treatment effect will be calculated as: FEV₁ after the tiotropium treatment period (L) - FEV₁ after the control observation period (L). |
At the end of the 3-month treatment period and at the end of the 3-month control period (specifically at Week 12 and Week 28 for Sequence A, or at Week 12 and Week 24 for Sequence B)
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Change from Baseline in Secondary Spirometric Parameters (FVC expressed in liters [L], PEF in liters per second [L/s], and MEF25-75 in liters per second [L/s])
時間枠：At the end of the 3-month treatment period and at the end of the 3-month control period (specifically at Week 12 and Week 28 for Sequence A, or at Week 12 and Week 24 for Sequence B)
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The absolute changes in Forced Vital Capacity (FVC, expressed in liters [L]), Peak Expiratory Flow (PEF, expressed in liters per second [L/s],), and Forced Expiratory Flow at 25%, 50%, and 75% of FVC (FEF25-75, expressed in liters per second [L/s],) evaluated between the end of the 3-month tiotropium treatment period and the end of the 3-month control observation period.
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At the end of the 3-month treatment period and at the end of the 3-month control period (specifically at Week 12 and Week 28 for Sequence A, or at Week 12 and Week 24 for Sequence B)
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Frequency of Acute Respiratory Exacerbations and Rescue Medication Use
時間枠：Continuously throughout both 3-month periods (treatment and control) and the 4-week washout phase, evaluated over a total span of up to 7 months per participant.
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The total number of acute respiratory exacerbations and the frequency of rescue medication (Short-acting Beta-2 Agonist - SABA) usage tracked via daily patient/parent diaries during the 3-month tiotropium treatment period compared to the 3-month control observation period.
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Continuously throughout both 3-month periods (treatment and control) and the 4-week washout phase, evaluated over a total span of up to 7 months per participant.
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協力者と研究者
捜査官
- 主任研究者：Jana Tuková, MUDr., Ph.D.、General University Hospital, Prague
研究記録日
主要日程の研究
研究開始 (推定)
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
- PRETIO-2026
- 2026-525773-39-00 (Ctis)
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?
IPD プランの説明
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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