Ipratropium Bromide in Peri-Operative COPD

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial.The trial aims to evaluate efficacy of nebulized ipratropium bromide in Chinese peri-operative patients with COPD under general anaesthesia.

Official Title
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Peri-operative Intervention With Nebulized Ipratropium Bromide in Chinese Patients With Chronic Obstructive Pulmonary Disease (COPD): a Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-centre Trial.

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: placebo
* Drug: ipratropium bromide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: All patients must sign an informed consent. Male or female patients aged >= 40 years and <= 80 years All patients must be diagnosed with COPD and must meet the following spirometric criterion: post-bronchodilator forced expiratory volume in 1 second (FEV1) < 70% of forced vital capacity (FVC) at Screening Visit (Visit 1). All patients have relatively stable COPD (i.e. have no COPD exacerbation within 4 weeks prior to Screening Visit). All patients are about to receive selective surgical procedures of lobectomy or right bilobectomy or segmentectomy under general anaesthesia, whilst the estimated time of surgical procedures lasts for not less than 2 hours, and the estimated time of general anaesthesia lasts for not less than 3 hours and not longer than 5 hours. Patients must be able to perform all study related procedures including technically acceptable pulmonary function tests (PFTs). Exclusion criteria: Patients who need maintenance treatment of bronchodilators (including anticholinergics, ß-agonists, xanthines). Patients with a recent history (i.e. six months or less) of myocardial infarction Patients with any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year Patients with symptomatic chronic heart failure (i.e. New York Heart Association functional class III-IV) Known narrow angle glaucoma Patients with prostatic hyperplasia or bladder neck obstruction with significant symptoms Patients with a history of asthma, allergic rhinitis or who have a blood eosinophil count >= 600 / mm3 (0.6×10^9/L). A repeat eosinophil count will not be conducted in these patients

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ipratropium<br>500 mcg four times a day | Drug: ipratropium bromide<br>* ipratropium bromide<br>|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Forced Expiratory Volume in 1 Second (FEV1) From Pre-bronchodilator at Baseline to Post-nebulization One Day Before the Surgery | Change of forced expiratory volume in 1 second (FEV1) from pre-bronchodilator at baseline to post-nebulization one day before the surgery (Treatment day 3). Measurements of FEV1 were performed using calibrated electronic spirometers. Equipment and techniques should conform to American Thoracic Society (ATS) criteria (P05-12782). At screening visit, pulmonary function testing (PFT) was performed at baseline and repeated 30 minutes following inhalation of 4 puffs of salbutamol hydrofluoroalkanes metered-dose inhaler (HFA MDI). At treatment day 3, pulmonary function testing was performed 60 minutes following the inhalation of investigational drug. Spirometry was conducted with the patient in a seated position having abstained from medications. The best of three efforts was defined as the highest FEV1 each obtained on any of three efforts meeting the ATS criteria and it was selected regardless of whether they came from different spirometric manoeuvres or the same manoeuvre. | Baseline and Treatment day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Forced Vital Capacity (FVC) From Pre-bronchodilator at Baseline to Post-nebulization One Day Before the Surgery | Change of forced vital capacity (FVC) from pre-bronchodilator at baseline to post-nebulization one day before the surgery (Treatment day 3). Measurements of FVC were performed using calibrated electronic spirometers. Equipment and techniques should conform to American Thoracic Society (ATS) criteria (P05-12782). At Visit 1, pulmonary function testing (PFT) was performed at baseline and repeated 30 minutes following inhalation of 4 puffs of salbutamol hydrofluoroalkanes metered-dose inhaler (HFA MDI). At Visit 3, pulmonary function testing was performed 60 minutes following the inhalation of investigational drug. Spirometry was conducted with the patient in a seated position having abstained from medications. The best of three efforts was defined as the highest FVC each obtained on any of three efforts meeting the ATS criteria and it was selected regardless of whether they came from different spirometric manoeuvres or the same manoeuvre. | Baseline and Treatment day 3 | 
| Change of Blood Gas Analyses From Pre-bronchodilator at Baseline to Post-nebulization One Day Before the Surgery: Arterial Oxygen Pressure (PaO2) Value | Change of blood gas analyses from pre-bronchodilator at baseline to post-nebulization one day before the surgery (Treatment day 3): arterial oxygen pressure (PaO2) value | Baseline and Treatment day 3 | 
| Change of Blood Gas Analyses From Pre-bronchodilator at Baseline to Post-nebulization One Day Before the Surgery: Oxygen Saturation | Change of blood gas analyses from pre-bronchodilator at baseline to post-nebulization one day before the surgery (Treatment day 3): Oxygen saturation | Baseline and Treatment day 3 | 
| Change of Blood Gas Analyses From Pre-bronchodilator at Baseline to Post-nebulization One Day Before the Surgery: Arterial Carbon Dioxide Pressure (PaCO2) Value | Change of blood gas analyses from pre-bronchodilator at baseline to post-nebulization one day before the surgery (Treatment day 3): arterial carbon dioxide pressure (PaCO2) value | Baseline and Treatment day 3 | 
| Main Post-operative Pulmonary Complications (Including Pneumonia, Atelectasis and Acute Respiratory Failure) Within Three Weeks After the Surgery | Number of patients with at least one main post-operative pulmonary complications (including pneumonia, atelectasis and acute respiratory failure) within three weeks after the surgery. Post-operative pneumonia was defined by the presence of the following criteria: persistent lung infiltrate on chest X-ray or chest computerized tomography (CT)-scan, white blood cell count >10,000 /mm3 and fever. Post-operative atelectasis was diagnosed by presence of atelectasis affecting one lobe or several lobes in chest X-ray test or chest CT-scan. Post-operative acute respiratory failure was defined by the presence of: PaO2 < 60 mmHg and/or PaCO2 > 50 mmHg while breathing air or other evidences which were considered as respiratory failure by investigators. | From surgery to 3 weeks post surgery, up to 21 days |