Clinical trial NCT04536675: Effect of Perioperative Bronchodilator in COPD Patients Undergoing Lung Cancer Surgery
Official title: Effect of Perioperative Fixed-dose Dual Bronchodilator Therapy on Post-operative Pulmonary Function Among Mild- to -Moderate COPD Patients Undergoing Lung Cancer Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Non Small Cell Lung Cancer
Keywords: Chronic obstructive pulmonary disease
Non-small cell lung cancer
Lobectomy
Dual bronchodilator therapy
Pulmonary function
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2020-09-03
Enrollment: 204
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a double-blind randomized controlled trial evaluating the effect of perioperative dual bronchodilator therapy on post-operative pulmonary function and health-related quality of life (QoL) in mild-to-moderate less symptomatic COPD patients undergoing lung cancer surgery.

Investigators hypothesized that dual bronchodilator, as compared with placebo, would prevent reduction of pulmonary function after surgical resection and improve postoperative health related QoL.


Eligibility criteria: Inclusion Criteria:

* Subjects of men or female over 40 years of age who are scheduled for curative pulmonary lobectomy due to confirmation (or high suspicion) of non-small cell lung cancer (NSCLC)
* Subjects waiting at least 14 days for scheduled pulmonary lobectomy
* Subjects who are newly diagnosed with COPD\* or who have not used any bronchodilators within the past 3 months, even if they have previously been diagnosed with COPD

  * COPD : Post-bronchodilator (Post-BD) FEV1/FVC \<0.7 and Post-BD FEV1 ≥70 %predicted (%pred)
* Subjects with dyspnea of 0 or 1 grade measured by modified Medical Research Council (mMRC)

Exclusion Criteria:

* Pregnancy: subjects of women who are pregnant, lactating, planning on becoming pregnant during the clinical trial, or of child bearing potential not using contraception methods
* COPD treatment/acute exacerbation: subjects who have been treated with COPD within the past 3 months or have experienced acute exacerbation of COPD within the past 1 month (Acute exacerbation of COPD is defined as the cases requiring antibiotics, oral corticosteroids, emergency treatment, or hospitalization due to at least one symptom from increased breathlessness, sputum volume, or sputum purulence)
* Other pulmonary diseases: subjects who are physician-diagnosed with asthma or Idiopathic Pulmonary Fibrosis (IPF)
* Lung cancer treatment: subjects who have been received neo-adjuvant treatment for lung cancer (chemotherapy, radiotherapy, or concurrent chemo-radiotherapy)
* Other diseases/abnormalities: subjects diagnosed with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities including medical condition corresponding to 'warnings and precautions' (such as coronary artery disease, acute myocardial infarction, cardiac arrhythmia, hypertension, convulsive disorders, thyrotoxicosis, hypokalemia, diabetes, narrow-angle glaucoma, urinary retention, prostatic hyperplasia, bladder-neck obstruction etc.) that are uncontrolled and/or with cancer within 5 years (Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.)
* Abnormal and clinically significant 12-Lead Eletrocardiogram (ECG): subjects with abnormal and clinically significant ECG findings (Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.)
* Contraindications: subjects with a history of allergy or hypersensitivity to any Long-Acting Muscarinic Antagonist (LAMA), Long-Acting Beta-Agonist (LABA), lactose/milk protein, stearic magnesium, with generic problems including galactose intolerance, Lapp lactose deficiency, or glucose-galactose malabsorption, or with contraindication of inhaled anticholinergic-containing drugs
* Mobility: subjects who are not able to walk independently without mobility assistance or other people

Primary outcomes:
measure: Post-bronchodilator FEV1 at 16 weeks
timeFrame: Postoperative 16 to 18 weeks (T3)
Secondary outcomes:
measure: Difference of predicted postoperative FEV1 and actual postoperative FEV1 at 16 weeks
timeFrame: Postoperative 16 to 18 weeks (T3) and baseline (T0)
measure: Difference of post-bronchodilator FEV1 between baseline and surgery
timeFrame: Baseline (T0) and before surgery (T1)
measure: Difference of post-bronchodilator FEV1 before surgery and at 3 weeks
timeFrame: Before surgery (T1) and postoperative 2 to 4 weeks (T2)
measure: Dyspnea and health-related quality of life at postoperative 3 and 16 weeks
timeFrame: Postoperative 2 to 4 weeks (T2) and postoperative 16 to 18 weeks (T3)
measure: Dyspnea and health-related quality of life at postoperative 3 and 16 weeks
timeFrame: Postoperative 2 to 4 weeks (T2) and postoperative 16 to 18 weeks (T3)
measure: Dyspnea and health-related quality of life at postoperative 3 and 16 weeks
timeFrame: Postoperative 2 to 4 weeks (T2) and postoperative 16 to 18 weeks (T3)
measure: Dyspnea and health-related quality of life at postoperative 3 and 16 weeks
timeFrame: Postoperative 2 to 4 weeks (T2) and postoperative 16 to 18 weeks (T3)
measure: Dyspnea and health-related quality of life at postoperative 3 and 16 weeks
timeFrame: Postoperative 2 to 4 weeks (T2) and postoperative 16 to 18 weeks (T3)
measure: Dyspnea and health-related quality of life at postoperative 3 and 16 weeks
timeFrame: Postoperative 2 to 4 weeks (T2) and postoperative 16 to 18 weeks (T3)
measure: Dyspnea and health-related quality of life at postoperative 3 and 16 weeks
timeFrame: Postoperative 2 to 4 weeks (T2) and postoperative 16 to 18 weeks (T3)
measure: Exercise tolerance at postoperative 3 and 16 weeks
timeFrame: Postoperative 2 to 4 weeks (T2) and 16 to 18 weeks (T3)
measure: Postoperative pulmonary and cardiac complication
timeFrame: Within 30 days and 90 days
measure: Length of hospital stay
timeFrame: From the admission for lung cancer surgery to discharge or death, whichever comes first
measure: COPD Acute exacerbation
timeFrame: Between randomization (T0) and postoperative 16 to 18 weeks (T3)
measure: Compliance
timeFrame: Between randomization (T0) and postoperative 16 to 18 weeks (T3)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References:
citation: Kobayashi S, Suzuki S, Niikawa H, Sugawara T, Yanai M. Preoperative use of inhaled tiotropium in lung cancer patients with untreated COPD. Respirology. 2009 Jul;14(5):675-9. doi: 10.1111/j.1440-1843.2009.01543.x. Epub 2009 May 19.
citation: Suzuki H, Sekine Y, Yoshida S, Suzuki M, Shibuya K, Takiguchi Y, Tatsumi K, Yoshino I. Efficacy of perioperative administration of long-acting bronchodilator on postoperative pulmonary function and quality of life in lung cancer patients with chronic obstructive pulmonary disease. Preliminary results of a randomized control study. Surg Today. 2010 Oct;40(10):923-30. doi: 10.1007/s00595-009-4196-1. Epub 2010 Sep 25.
citation: Bolukbas S, Eberlein M, Eckhoff J, Schirren J. Short-term effects of inhalative tiotropium/formoterol/budenoside versus tiotropium/formoterol in patients with newly diagnosed chronic obstructive pulmonary disease requiring surgery for lung cancer: a prospective randomized trial. Eur J Cardiothorac Surg. 2011 Jun;39(6):995-1000. doi: 10.1016/j.ejcts.2010.09.025. Epub 2010 Oct 22.