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

NCT ID: NCT04923412

Last Updated: 2022-10-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

214 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-01

Study Completion Date

2023-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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Lung Cancer Vagus Nerve Injuries Cough

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pulmonary branch of vagus nerve preserved

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

Group Type EXPERIMENTAL

Pulmonary branch of vagus nerve preserved

Intervention Type 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 not-preserved

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

Group Type EXPERIMENTAL

Pulmonary branch of vagus nerve not preserved

Intervention Type 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.

Interventions

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Pulmonary branch of vagus nerve preserved

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

Intervention Type PROCEDURE

Pulmonary branch of vagus nerve not preserved

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.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. Clinically suspicious of non-small cell lung cancer or tissue confirmed preoperatively
3. Clinical stage T1-3/N0-1/M0
4. Preoperative ECOG performance status 0-1
5. Preoperative ASA class I-III
6. Preoperative pulmonary function test FEV1 ≥ 60%, DLCO ≥ 60%
7. Patients expected to achieve R0 (complete resection) via simple lobectomy and mediastinal lymph node dissection

Exclusion Criteria

1. Patients who smoked within 2 weeks prior to operation
2. Patients who received antitussives and expectorants 2 weeks prior to operation
3. Patients who are pregnant or breast feeding
4. Patients with severe or uncontrolled psychological disorders
5. Patients with severe pulmonary adhesion
6. Patients who are ineligible for minimally invasive surgery; thoracotomy conversion
7. Patients diagnosed with other malignancies within 2 years prior to operation
8. Patients who received chemotherapy or radiotherapy within 6 months prior to operation
9. Patients suspicious of clinical N2 or received neoadjuvant therapy prior to operation
10. Patients with cough-related diseases; COPD, asthma, ILD, GERD
11. Patients suspicious of lymph node metastasis/invasion around vagus nerve during the preoperative clinical staging evaluation
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Seoul National University Bundang Hospital

OTHER

Sponsor Role lead

Responsible Party

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Kwhanmien Kim

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kwhanmien Kim, MD. PhD

Role: STUDY_DIRECTOR

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

Locations

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Seoul National University

Seongnam-si, Bundang, South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Kwhanmien Kim, MD. PhD

Role: CONTACT

+82-31-787-7130

Facility Contacts

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Beatrice C Shih, MD

Role: primary

821091094533

References

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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.

Reference Type BACKGROUND
PMID: 25749761 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31170972 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30962991 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24300131 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30416784 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31656677 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23562675 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14769722 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15620960 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25383207 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22643666 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22134070 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30883022 (View on PubMed)

Other Identifiers

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B-2007-625-007

Identifier Type: -

Identifier Source: org_study_id

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