Vagus Nerve Preservation and Chronic Cough in Non-small Cell Lung Cancer Surgery
2022年10月24日 更新者：Kwhanmien Kim、Seoul National University Bundang Hospital
Prospective Randomized Controlled Study on the Effects of Vagus Nerve Pulmonary Branch Preservation During Video-assisted Thoracic Surgery Lobectomy in Non-small Cell Lung Cancer: Can it Decrease Postoperative Cough and Pulmonary Complications
Lung cancer is the leading cause of cancer death worldwide. Surgical resection is the main treatment for resectable non-small-cell lung cancer (NSCLC), and lobectomy with systemic mediastinal lymph node dissection is the standard surgical method. However, a significant number of patients experience postoperative chronic cough; it is observed in about 60% of patients during the first year of outpatient clinic follow-up, and persistently lasts in about 24.7-50% during the 5 year follow-up period.
Several studies showed the association between vagus nerve and chronic cough. The bronchopulmonary vagal afferent C-fibers are responsible for cough, chest tightness and reflex bronchoconstrictions. It is expected that during the mediastinal lymph node dissection, the inevitable injuries to the pulmonary branch of vagus nerve is largely responsible for development of chronic cough. In other words, preservation of pulmonary branch of vagus nerve may reduce the incidence of chronic cough and relevant detrimental effects on quality of life.
Therefore, this prospective, randomized and controlled clinical study, aims to evaluate the effect of vagus nerve preservation on postoperative chronic cough in patients undergoing lobectomy with mediastinal lymph node dissection. In addition, the feasibility and oncologic safety of preserving pulmonary branch of vagus nerve during mediastinal lymph node dissection with minimally invasive surgery compared with conventional mediastinal lymph node dissection with minimally invasive surgery will also be investigated.
This trial will provide a new basis for oncologically feasible, safe and effective new surgical technique for mediastinal lymph node dissection in patients with early lung cancer undergoing minimally invasive surgery. Furthermore, the preventive effect of vagus nerve preservation on incidence of chronic cough will be objectively be proven and thus help to broaden the current knowledge of the role of vagus nerve and postoperative chronic cough.
調査の概要
状態
募集
研究の種類
介入
入学 (予想される)
214
段階
- 適用できない
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Kwhanmien Kim, MD. PhD
- 電話番号：+82-31-787-7130
- メール：kmkim0070@snubh.org
研究場所
-
-
Bundang
-
Seongnam-si、Bundang、大韓民国、13620
- 募集
- Seoul National University
-
コンタクト：
- Beatrice C Shih, MD
- 電話番号：821091094533
- メール：82430@snubh.org
-
主任研究者：
- Kwhanmien Kim, MD.PhD.
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～80年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Subjects clearly understand the purpose of the study, are willing and able to comply with the requirements to complete the study, and can sign the informed consent.
- Clinically suspicious of non-small cell lung cancer or tissue confirmed preoperatively
- Clinical stage T1-3/N0-1/M0
- Preoperative ECOG performance status 0-1
- Preoperative ASA class I-III
- Preoperative pulmonary function test FEV1 ≥ 60%, DLCO ≥ 60%
- Patients expected to achieve R0 (complete resection) via simple lobectomy and mediastinal lymph node dissection
Exclusion Criteria:
- Patients who smoked within 2 weeks prior to operation
- Patients who received antitussives and expectorants 2 weeks prior to operation
- Patients who are pregnant or breast feeding
- Patients with severe or uncontrolled psychological disorders
- Patients with severe pulmonary adhesion
- Patients who are ineligible for minimally invasive surgery; thoracotomy conversion
- Patients diagnosed with other malignancies within 2 years prior to operation
- Patients who received chemotherapy or radiotherapy within 6 months prior to operation
- Patients suspicious of clinical N2 or received neoadjuvant therapy prior to operation
- Patients with cough-related diseases; COPD, asthma, ILD, GERD
- Patients suspicious of lymph node metastasis/invasion around vagus nerve during the preoperative clinical staging evaluation
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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：並列代入
- 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：Pulmonary branch of vagus nerve preserved
Pulmonary branch of vagus nerve is preserved during the mediastinal lymph node dissection using minimally invasive surgery
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During the mediastinal lymph node dissection using minimally invasive surgery, efforts to preserve the pulmonary branch of vagus nerve is made.
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実験的：Pulmonary branch of vagus nerve not-preserved
Pulmonary branch of vagus nerve is not preserved during the mediastinal lymph node dissection using minimally invasive surgery
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During the mediastinal lymph node dissection using minimally invasive surgery, efforts to preserve the pulmonary branch of vagus nerve is not made/ can be severed.
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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 |
|---|---|---|
|
Qualitative measurement of postoperative cough
時間枠：Preoperative day
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Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
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Preoperative day
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Qualitative measurement of postoperative cough
時間枠：Postoperative day (discharge day, an average of 1 week)
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Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
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Postoperative day (discharge day, an average of 1 week)
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Qualitative measurement of postoperative cough
時間枠：Postoperative 1 month follow up at outpatient clinic
|
Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
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Postoperative 1 month follow up at outpatient clinic
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Qualitative measurement of postoperative cough
時間枠：Postoperative 2 month follow up at outpatient clinic
|
Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
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Postoperative 2 month follow up at outpatient clinic
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Qualitative measurement of postoperative cough
時間枠：Postoperative 6 month follow up at outpatient clinic
|
Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
|
Postoperative 6 month follow up at outpatient clinic
|
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Qualitative measurement of postoperative cough
時間枠：Postoperative 12 month follow up at outpatient clinic
|
Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
|
Postoperative 12 month follow up at outpatient clinic
|
|
Quantitative measurement of postoperative cough
時間枠：Preoperative day
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
|
Preoperative day
|
|
Quantitative measurement of postoperative cough
時間枠：Postoperative day (discharge day, an average of 1 week)
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
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Postoperative day (discharge day, an average of 1 week)
|
|
Quantitative measurement of postoperative cough
時間枠：Postoperative 1 month follow up at outpatient clinic
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
|
Postoperative 1 month follow up at outpatient clinic
|
|
Quantitative measurement of postoperative cough
時間枠：Postoperative 2 month follow up at outpatient clinic
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
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Postoperative 2 month follow up at outpatient clinic
|
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Quantitative measurement of postoperative cough
時間枠：Postoperative 6 month follow up at outpatient clinic
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
|
Postoperative 6 month follow up at outpatient clinic
|
|
Quantitative measurement of postoperative cough
時間枠：Postoperative 12 month follow up at outpatient clinic
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
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Postoperative 12 month follow up at outpatient clinic
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Serum TRPA1, TRPV1, bradykinin, PGE2 measurements
時間枠：Preoperative day
|
Measurement of TRPA1 (ng/mL), TRPV1 (ng/mL), bradykinin (pg/mL), PGE2 (pg/mL) (released from C-fibers) via enzyme-linked immunosorbent assay (ELISA) test to quantitatively measure the injures of the vagus nerve during the mediastinal lymph node dissection.
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Preoperative day
|
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Serum TRPA1, TRPV1, bradykinin, PGE2 measurements
時間枠：Postoperative 1 day
|
Measurement of TRPA1 (ng/mL), TRPV1 (ng/mL), bradykinin (pg/mL), PGE2 (pg/mL) (released from C-fibers) via enzyme-linked immunosorbent assay (ELISA) test to quantitatively measure the injures of the vagus nerve during the mediastinal lymph node dissection.
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Postoperative 1 day
|
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Serum TRPA1, TRPV1, bradykinin, PGE2 measurements
時間枠：Postoperative 2 month follow up at outpatient clinic
|
Measurement of TRPA1 (ng/mL), TRPV1 (ng/mL), bradykinin (pg/mL), PGE2 (pg/mL) (released from C-fibers) via enzyme-linked immunosorbent assay (ELISA) test to quantitatively measure the injures of the vagus nerve during the mediastinal lymph node dissection.
|
Postoperative 2 month follow up at outpatient clinic
|
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Pulmonary function test
時間枠：Preoperative day
|
Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function
|
Preoperative day
|
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Pulmonary function test
時間枠：Postoperative 1 month follow up at outpatient clinic
|
Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function
|
Postoperative 1 month follow up at outpatient clinic
|
|
Pulmonary function test
時間枠：Postoperative 2 month follow up at outpatient clinic
|
Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function
|
Postoperative 2 month follow up at outpatient clinic
|
|
Pulmonary function test
時間枠：Postoperative 6 month follow up at outpatient clinic
|
Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function
|
Postoperative 6 month follow up at outpatient clinic
|
|
Pulmonary function test
時間枠：Postoperative 12 month follow up at outpatient clinic
|
Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function
|
Postoperative 12 month follow up at outpatient clinic
|
|
Incidence of postoperative pulmonary complications, hospital stay and readmission, ICU care
時間枠：from admission for operation to until the date of first documented postoperative complication or readmission, whichever came first), assessed up to 30 days
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from admission for operation to until the date of first documented postoperative complication or readmission, whichever came first), assessed up to 30 days
|
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Histopathologic review of the total number of mediastinal lymph node dissected
時間枠：through study completion, an average of 1 year
|
Total number of dissected mediastinal lymph nodes and metastatic lymph nodes will be analyzed.
Patient's preoperative clinical N stage and pathologic N stage will be compared; if pathologic N stage is higher than that of the clinical N stage, it will be considered as nodal upstaging.
|
through study completion, an average of 1 year
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- スタディディレクター：Kwhanmien Kim, MD. PhD、Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Zhu YF, Wu SB, Zhou MQ, Xie MR, Xiong R, Xu SB, Xu GW. Increased expression of TRPV1 in patients with acute or chronic cough after lung cancer surgery. Thorac Cancer. 2019 Apr;10(4):988-991. doi: 10.1111/1759-7714.13042. Epub 2019 Mar 18.
- Sarna L, Evangelista L, Tashkin D, Padilla G, Holmes C, Brecht ML, Grannis F. Impact of respiratory symptoms and pulmonary function on quality of life of long-term survivors of non-small cell lung cancer. Chest. 2004 Feb;125(2):439-45. doi: 10.1378/chest.125.2.439.
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- Al-Shamlan F, El-Hashim AZ. Bradykinin sensitizes the cough reflex via a B2 receptor dependent activation of TRPV1 and TRPA1 channels through metabolites of cyclooxygenase and 12-lipoxygenase. Respir Res. 2019 Jun 6;20(1):110. doi: 10.1186/s12931-019-1060-8.
- Chen S, Huang S, Yu S, Han Z, Gao L, Shen Z, Kang M. The clinical value of a new method of functional lymph node dissection in video-assisted thoracic surgery right non-small cell lung cancer radical resection. J Thorac Dis. 2019 Feb;11(2):477-487. doi: 10.21037/jtd.2019.01.15.
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- Poghosyan H, Sheldon LK, Leveille SG, Cooley ME. Health-related quality of life after surgical treatment in patients with non-small cell lung cancer: a systematic review. Lung Cancer. 2013 Jul;81(1):11-26. doi: 10.1016/j.lungcan.2013.03.013. Epub 2013 Apr 4.
- Sawabata N, Maeda H, Takeda S, Inoue M, Koma M, Tokunaga T, Matsuda H. Persistent cough following pulmonary resection: observational and empiric study of possible causes. Ann Thorac Surg. 2005 Jan;79(1):289-93. doi: 10.1016/j.athoracsur.2004.06.045.
- Spinou A, Birring SS. An update on measurement and monitoring of cough: what are the important study endpoints? J Thorac Dis. 2014 Oct;6(Suppl 7):S728-34. doi: 10.3978/j.issn.2072-1439.2014.10.08.
- Watanabe A, Nakazawa J, Miyajima M, Harada R, Nakashima S, Mawatari T, Higami T. Thoracoscopic mediastinal lymph node dissection for lung cancer. Semin Thorac Cardiovasc Surg. 2012 Spring;24(1):68-73. doi: 10.1053/j.semtcvs.2012.03.002.
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2021年7月1日
一次修了 (予想される)
2023年6月30日
研究の完了 (予想される)
2023年6月30日
試験登録日
最初に提出
2021年5月23日
QC基準を満たした最初の提出物
2021年6月6日
最初の投稿 (実際)
2021年6月11日
学習記録の更新
投稿された最後の更新 (実際)
2022年10月26日
QC基準を満たした最後の更新が送信されました
2022年10月24日
最終確認日
2022年10月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。