Trial Outcomes & Findings for Ipratropium Bromide in Peri-Operative COPD (NCT NCT01943552)
NCT ID: NCT01943552
Last Updated: 2016-10-25
Results Overview
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.
COMPLETED
PHASE4
192 participants
Baseline and Treatment day 3
2016-10-25
Participant Flow
192 patients were randomized in a 1:1 ratio(96 patients in each group).1 patient each in both treatment groups did not receive the treatment.1 patient, who was randomized to the placebo group, but received nebulized ipratropium bromide, so the actual numbers of patients received nebulized ipratropium bromide and placebo were 96 and 94 respectively
This was randomised, double-blind, placebo-controlled, parallel-group, multicentre trial which aims to evaluate efficacy and safety of nebulized ipratropium bromide in Chinese peri-operative patients with chronic obstructive pulmonary disease (COPD) under general anaesthesia.
Participant milestones
| Measure |
Nebulized Ipratropium Bromide
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
|---|---|---|
|
Overall Study
STARTED
|
96
|
94
|
|
Overall Study
COMPLETED
|
71
|
69
|
|
Overall Study
NOT COMPLETED
|
25
|
25
|
Reasons for withdrawal
| Measure |
Nebulized Ipratropium Bromide
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
6
|
6
|
|
Overall Study
Other Reasons
|
16
|
17
|
Baseline Characteristics
Ipratropium Bromide in Peri-Operative COPD
Baseline characteristics by cohort
| Measure |
Nebulized Ipratropium Bromide
n=96 Participants
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
n=94 Participants
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
Total
n=190 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.4 Years
STANDARD_DEVIATION 6.5 • n=99 Participants
|
62.4 Years
STANDARD_DEVIATION 6.4 • n=107 Participants
|
62.9 Years
STANDARD_DEVIATION 6.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
83 Participants
n=99 Participants
|
85 Participants
n=107 Participants
|
168 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline and Treatment day 3Population: Full analysis set (FAS): All patients in the treated set who had observed analysable data in at least one efficacy endpoint. (Only patients with observed cases (OC) values were analysed)
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.
Outcome measures
| Measure |
Nebulized Ipratropium Bromide
n=94 Participants
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
n=89 Participants
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
|---|---|---|
|
Change of Forced Expiratory Volume in 1 Second (FEV1) From Pre-bronchodilator at Baseline to Post-nebulization One Day Before the Surgery
|
169.9 ml
Standard Error 29.07
|
15.0 ml
Standard Error 29.35
|
SECONDARY outcome
Timeframe: Baseline and Treatment day 3Population: Full analysis set (FAS). (Only patients with observed cases (OC) values were analysed)
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.
Outcome measures
| Measure |
Nebulized Ipratropium Bromide
n=94 Participants
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
n=89 Participants
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
|---|---|---|
|
Change of Forced Vital Capacity (FVC) From Pre-bronchodilator at Baseline to Post-nebulization One Day Before the Surgery
|
59.4 ml
Standard Error 48.76
|
8.5 ml
Standard Error 49.27
|
SECONDARY outcome
Timeframe: Baseline and Treatment day 3Population: Full analysis set (FAS). (Only patients with observed cases (OC) values were analysed)
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
Outcome measures
| Measure |
Nebulized Ipratropium Bromide
n=89 Participants
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
n=80 Participants
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
|---|---|---|
|
Change of Blood Gas Analyses From Pre-bronchodilator at Baseline to Post-nebulization One Day Before the Surgery: Arterial Oxygen Pressure (PaO2) Value
|
3.2 mmHg
Standard Error 1.92
|
0.5 mmHg
Standard Error 1.92
|
SECONDARY outcome
Timeframe: Baseline and Treatment day 3Population: Full analysis set (FAS). (Only patients with observed cases (OC) values were analysed)
Change of blood gas analyses from pre-bronchodilator at baseline to post-nebulization one day before the surgery (Treatment day 3): Oxygen saturation
Outcome measures
| Measure |
Nebulized Ipratropium Bromide
n=89 Participants
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
n=81 Participants
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
|---|---|---|
|
Change of Blood Gas Analyses From Pre-bronchodilator at Baseline to Post-nebulization One Day Before the Surgery: Oxygen Saturation
|
0.6 Percentage of Oxygen
Standard Error 0.25
|
0.3 Percentage of Oxygen
Standard Error 0.25
|
SECONDARY outcome
Timeframe: Baseline and Treatment day 3Population: Full analysis set (FAS). (Only patients with observed cases (OC) values were analysed)
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
Outcome measures
| Measure |
Nebulized Ipratropium Bromide
n=89 Participants
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
n=80 Participants
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
|---|---|---|
|
Change of Blood Gas Analyses From Pre-bronchodilator at Baseline to Post-nebulization One Day Before the Surgery: Arterial Carbon Dioxide Pressure (PaCO2) Value
|
-0.1 mmHg
Standard Error 0.51
|
-0.5 mmHg
Standard Error 0.52
|
SECONDARY outcome
Timeframe: From surgery to 3 weeks post surgery, up to 21 daysPopulation: Surgery complete set (SCS): All patients who completed 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.
Outcome measures
| Measure |
Nebulized Ipratropium Bromide
n=77 Participants
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
n=78 Participants
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
|---|---|---|
|
Main Post-operative Pulmonary Complications (Including Pneumonia, Atelectasis and Acute Respiratory Failure) Within Three Weeks After the Surgery
|
8 Participants
|
14 Participants
|
Adverse Events
Nebulized Ipratropium Bromide
Placebo
Serious adverse events
| Measure |
Nebulized Ipratropium Bromide
n=96 participants at risk
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
n=94 participants at risk
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
|---|---|---|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
1.1%
1/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
|
General disorders
Pyrexia
|
1.0%
1/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
0.00%
0/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
|
Immune system disorders
Anaphylactic shock
|
1.0%
1/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
0.00%
0/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
|
Infections and infestations
Post procedural pneumonia
|
0.00%
0/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
1.1%
1/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
1.0%
1/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
1.1%
1/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
1.0%
1/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
1.1%
1/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.0%
1/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
0.00%
0/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
Other adverse events
| Measure |
Nebulized Ipratropium Bromide
n=96 participants at risk
500 microgram (mcg) ipratropium bromide solution was administered orally via nebulizer four times a day up to 11 days.
|
Placebo
n=94 participants at risk
4 milliliter (ml) normal saline was administered orally via nebulizer four times a day up to 11 days.
|
|---|---|---|
|
Infections and infestations
Post procedural pneumonia
|
2.1%
2/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
9.6%
9/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
|
Injury, poisoning and procedural complications
Wound complication
|
8.3%
8/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
10.6%
10/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
|
Respiratory, thoracic and mediastinal disorders
Sputum retention
|
4.2%
4/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
7.4%
7/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
|
Vascular disorders
Hypertension
|
5.2%
5/96 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
1.1%
1/94 • From first drug administration until 14 days after the last drug administration, up to 32 days
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER