Vagus Nerve Preservation and Chronic Cough in Non-small Cell Lung Cancer Surgery

NCT04923412 | Unknown

• 1 other identifier: B-2007-625-007
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lung Cancer; Vagus Nerve Injuries; Cough

Outcome Measures

Primary Outcomes (12)

• Qualitative measurement of postoperative cough

  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.

  Preoperative day

• Qualitative measurement of postoperative cough

  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 day (discharge day, an average of 1 week)

• Qualitative measurement of postoperative cough

  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 1 month follow up at outpatient clinic

• Qualitative measurement of postoperative cough

  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 2 month follow up at outpatient clinic

• Qualitative measurement of postoperative cough

  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

• Qualitative measurement of postoperative cough

  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

  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

  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 day (discharge day, an average of 1 week)

• Quantitative measurement of postoperative cough

  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

  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 2 month follow up at outpatient clinic

• Quantitative measurement of postoperative cough

  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

  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 12 month follow up at outpatient clinic

Secondary Outcomes (10)

• Serum TRPA1, TRPV1, bradykinin, PGE2 measurements

  Preoperative day

• Serum TRPA1, TRPV1, bradykinin, PGE2 measurements

  Postoperative 1 day

• Serum TRPA1, TRPV1, bradykinin, PGE2 measurements

  Postoperative 2 month follow up at outpatient clinic

• Pulmonary function test

  Preoperative day

• Pulmonary function test

  Postoperative 1 month follow up at outpatient clinic

Study Arms (2)

Pulmonary branch of vagus nerve preserved

EXPERIMENTAL

Pulmonary branch of vagus nerve is preserved during the mediastinal lymph node dissection using minimally invasive surgery

Procedure: Pulmonary branch of vagus nerve preserved

Pulmonary branch of vagus nerve not-preserved

EXPERIMENTAL

Pulmonary branch of vagus nerve is not preserved during the mediastinal lymph node dissection using minimally invasive surgery

Procedure: Pulmonary branch of vagus nerve not preserved

Interventions

Pulmonary branch of vagus nerve preserved PROCEDURE

During the mediastinal lymph node dissection using minimally invasive surgery, efforts to preserve the pulmonary branch of vagus nerve is made.

Pulmonary branch of vagus nerve preserved

Pulmonary branch of vagus nerve not preserved PROCEDURE

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.

Pulmonary branch of vagus nerve not-preserved

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Bundang Hospital: lead

Study Sites (1)

Seoul National University

Seongnam-si, Bundang, 13620, South Korea

RECRUITING

Related Publications (13)

• Kwon JW, Moon JY, Kim SH, Song WJ, Kim MH, Kang MG, Lim KH, Lee SH, Lee SM, Lee JY, Kwon HS, Kim KM, Kim SH, Kim SH, Jeong JW, Kim CW, Cho SH, Lee BJ; Work Group for Chronic Cough, the Korean Academy of Asthma, Allergy and Clinical Immunology. Reliability and validity of a korean version of the leicester cough questionnaire. Allergy Asthma Immunol Res. 2015 May;7(3):230-3. doi: 10.4168/aair.2015.7.3.230. Epub 2014 Dec 18.

  PMID: 25749761 BACKGROUND

• 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.

  PMID: 31170972 BACKGROUND

• 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.

  PMID: 30962991 BACKGROUND

• Huang J, Luo Q, Tan Q, Lin H, Qian L, Ding Z. Evaluation of the surgical fat-filling procedure in the treatment of refractory cough after systematic mediastinal lymphadenectomy in patients with right lung cancer. J Surg Res. 2014 Apr;187(2):490-5. doi: 10.1016/j.jss.2013.10.062. Epub 2013 Nov 5.

  PMID: 24300131 BACKGROUND

• Lin R, Che G. Risk factors of cough in non-small cell lung cancer patients after video-assisted thoracoscopic surgery. J Thorac Dis. 2018 Sep;10(9):5368-5375. doi: 10.21037/jtd.2018.08.54.

  PMID: 30416784 BACKGROUND

• Liu Z, Liu Y, Xie C, Yang J, Zeng B, Yeung SJ, Cheng C. Vagus nerve and phrenic nerve guided systematic nodal dissection for lung cancer. J Thorac Dis. 2019 Sep;11(9):4021-4027. doi: 10.21037/jtd.2019.08.80. No abstract available.

  PMID: 31656677 BACKGROUND

• 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.

  PMID: 23562675 BACKGROUND

• 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.

  PMID: 14769722 BACKGROUND

• 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.

  PMID: 15620960 BACKGROUND

• 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.

  PMID: 25383207 BACKGROUND

• 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.

  PMID: 22643666 BACKGROUND

• Yang P, Cheville AL, Wampfler JA, Garces YI, Jatoi A, Clark MM, Cassivi SD, Midthun DE, Marks RS, Aubry MC, Okuno SH, Williams BA, Nichols FC, Trastek VF, Sugimura H, Sarna L, Allen MS, Deschamps C, Sloan JA. Quality of life and symptom burden among long-term lung cancer survivors. J Thorac Oncol. 2012 Jan;7(1):64-70. doi: 10.1097/JTO.0b013e3182397b3e.

  PMID: 22134070 BACKGROUND

• 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.

  PMID: 30883022 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Vagus Nerve Injuries; Cough

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Cranial Nerve Injuries; Cranial Nerve Diseases; Nervous System Diseases; Vagus Nerve Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Kwhanmien Kim, MD. PhD

  Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital

  STUDY DIRECTOR

Central Study Contacts

Kwhanmien Kim, MD. PhD

CONTACT

+82-31-787-7130; kmkim0070@snubh.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 214 patients will be divided into two groups. 1. Control group (N=107): Effort to preserve the pulmonary branch of vagus nerve preservation is not made in this group during mediastinal lymph node dissection 2. Treatment group (N=107): Effort to preserve the pulmonary branch of vagus nerve preservation is made in this group during mediastinal lymph node dissection

Study Record Dates

• First Submitted: May 23, 2021
• First Posted: June 11, 2021
• Study Start: July 1, 2021
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: October 26, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)