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

Not Applicable

Recruiting

• Conditions: Cough; Vagus Nerve Injuries; Lung Cancer
• Interventions: Procedure: Pulmonary branch of vagus nerve preserved; Procedure: Pulmonary branch of vagus nerve not preserved

• Registration Number: NCT04923412
• Lead Sponsor: Seoul National University Bundang Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-05-23
• Study First Submitted QC: 2021-06-06
• Study First Posted: 2021-06-11
• Study Start: 2021-07-01
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-24
• Last Update Posted: 2022-10-26
• Primary Completion: 2023-06-30
• Study Completion: 2023-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 214

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Qualitative measurement of postoperative cough	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.
Quantitative measurement of postoperative cough	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.

Secondary Outcome Measures

Name	Time	Method
Serum TRPA1, TRPV1, bradykinin, PGE2 measurements	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.
Histopathologic review of the total number of mediastinal lymph node dissected	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.
Pulmonary function test	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
Incidence of postoperative pulmonary complications, hospital stay and readmission, ICU care	from admission for operation to until the date of first documented postoperative complication or readmission, whichever came first), assessed up to 30 days

Trial Locations

Locations (1)

Seoul National University; 🇰🇷 Seongnam-si, Bundang, Korea, Republic of