Trial Outcomes & Findings for Exacerbation Study (NCT NCT00845728)
NCT ID: NCT00845728
Last Updated: 2013-11-19
Results Overview
The primary objective of the study was to demonstrate the non-inferiority of indacaterol vs. tiotropium with respect to 24 hour post dose (trough) FEV1 after 12 weeks of treatment in patients with severe COPD. Trough FEV1 was defined as the average of the 23 hours 10 min and the 23 hours 45 min post dose values. Trough FEV1 was analyzed using a mixed model for the PPS-S. The model contained treatment as a fixed effect with the baseline FEV1, FEV1 prior to inhalation and FEV1 15 min post-inhalation of salbutamol/albuterol (components of SABA reversibility at Visit 2), FEV1 prior to inhalation and FEV1 60 min post-inhalation of ipratropium (components of anti-cholinergic reversibility at Visit 3) as covariates. Smoking history (current or ex-smoker) was included as a factor in the model.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
3439 participants
Primary outcome timeframe
12 weeks
Results posted on
2013-11-19
Participant Flow
3,444 patients were randomized, but only 3,439 received treatment as 5 patients were mis-randomized.
Participant milestones
| Measure |
Indacaterol
Indacaterol 150 μg o.d., delivered via SDDPI o.d. plus placebo to tiotropium o.d.
delivered via the manufacturer's proprietary inhalation device (Handihaler®)
|
Tiotropium
Tiotropium 18 μg o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®) plus placebo to indacaterol o.d. delivered via SDDPI
|
|---|---|---|
|
Overall Study
STARTED
|
1723
|
1721
|
|
Overall Study
Exposed
|
1721
|
1718
|
|
Overall Study
COMPLETED
|
1337
|
1379
|
|
Overall Study
NOT COMPLETED
|
386
|
342
|
Reasons for withdrawal
| Measure |
Indacaterol
Indacaterol 150 μg o.d., delivered via SDDPI o.d. plus placebo to tiotropium o.d.
delivered via the manufacturer's proprietary inhalation device (Handihaler®)
|
Tiotropium
Tiotropium 18 μg o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®) plus placebo to indacaterol o.d. delivered via SDDPI
|
|---|---|---|
|
Overall Study
Abnormal laboratory value (s)
|
2
|
2
|
|
Overall Study
Patient's inability to use the device
|
4
|
6
|
|
Overall Study
Abnormal test procedure result (s)
|
7
|
2
|
|
Overall Study
Lost to Follow-up
|
22
|
13
|
|
Overall Study
Death
|
24
|
26
|
|
Overall Study
Administrative Problems
|
34
|
26
|
|
Overall Study
Protocol Violation
|
36
|
24
|
|
Overall Study
Lack of Efficacy
|
51
|
39
|
|
Overall Study
Adverse Event
|
101
|
96
|
|
Overall Study
Withdrawal by Subject
|
105
|
108
|
Baseline Characteristics
Exacerbation Study
Baseline characteristics by cohort
| Measure |
Indacaterol
n=1721 Participants
Indacaterol 150 μg o.d., delivered via SDDPI o.d. plus placebo to tiotropium o.d.
delivered via the manufacturer's proprietary inhalation device (Handihaler®)
|
Tiotropium
n=1718 Participants
Tiotropium 18 μg o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®) plus placebo to indacaterol o.d. delivered via SDDPI
|
Total
n=3439 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
<65 years
|
929 Participants
n=93 Participants
|
909 Participants
n=4 Participants
|
1838 Participants
n=27 Participants
|
|
Age, Customized
≥ 65 years
|
792 Participants
n=93 Participants
|
809 Participants
n=4 Participants
|
1601 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
377 Participants
n=93 Participants
|
405 Participants
n=4 Participants
|
782 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
1344 Participants
n=93 Participants
|
1313 Participants
n=4 Participants
|
2657 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Per-Protocol Set for Spirometry (PPS-S) This set included Full Analysis Set (FAS) patients without any major protocol deviations or non-protocol deviation criteria that could affect the respective analysis of efficacy.
The primary objective of the study was to demonstrate the non-inferiority of indacaterol vs. tiotropium with respect to 24 hour post dose (trough) FEV1 after 12 weeks of treatment in patients with severe COPD. Trough FEV1 was defined as the average of the 23 hours 10 min and the 23 hours 45 min post dose values. Trough FEV1 was analyzed using a mixed model for the PPS-S. The model contained treatment as a fixed effect with the baseline FEV1, FEV1 prior to inhalation and FEV1 15 min post-inhalation of salbutamol/albuterol (components of SABA reversibility at Visit 2), FEV1 prior to inhalation and FEV1 60 min post-inhalation of ipratropium (components of anti-cholinergic reversibility at Visit 3) as covariates. Smoking history (current or ex-smoker) was included as a factor in the model.
Outcome measures
| Measure |
Indacaterol
n=1450 Participants
Indacaterol 150 μg o.d., delivered via SDDPI o.d. plus placebo to tiotropium o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®)
|
Tiotropium
n=1467 Participants
Tiotropium 18 μg o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®) plus placebo to indacaterol o.d. delivered via SDDPI
|
|---|---|---|
|
Trough Forced Expiratory Volume in 1 Second (FEV1).
|
1.134 Liters
Standard Error 0.0008
|
1.145 Liters
Standard Error 0.0008
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Per-Protocol Set for Exacerbations (PPS-E). This set included Full Analysis Set (FAS) patients without any major protocol deviations or non-protocol deviation criteria that could affect the respective analysis of efficacy.
COPD exacerbations were defined as :Worsening of 2 or more major symptoms for at least 2 consecutive days: dyspnea; sputum volume; suputum purulence AND requiring treatment with systemic corticosteroids and/or antibiotics OR Worsening of any 1 major symptom together with any 1 of the following minor symptoms for at least 2 consecutive days: Sore throat; colds; fever without other cause; increased cough; increase wheeze AND requiring treatment with systemic glucocorticosteroids and/or antibiotics. The rate was analyzed using a linear model assuming a negative binomial distribution for the PPS-E. The time at risk for a patient was defined as the length of time the patient was in the study and the log(length of time in the study) was used as the offset variable in the model.
Outcome measures
| Measure |
Indacaterol
n=1675 Participants
Indacaterol 150 μg o.d., delivered via SDDPI o.d. plus placebo to tiotropium o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®)
|
Tiotropium
n=1675 Participants
Tiotropium 18 μg o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®) plus placebo to indacaterol o.d. delivered via SDDPI
|
|---|---|---|
|
Rate of COPD Exacerbations
|
0.79 Exacerbations per patient per year
|
0.61 Exacerbations per patient per year
|
Adverse Events
IndIndacaterol
Serious events: 263 serious events
Other events: 890 other events
Deaths: 0 deaths
Tiotropium
Serious events: 255 serious events
Other events: 793 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
IndIndacaterol
n=1721 participants at risk
Indacaterol 150 μg o.d., delivered via SDDPI o.d. plus placebo to tiotropium o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®)
|
Tiotropium
n=1718 participants at risk
Tiotropium 18 μg o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®) plus placebo to indacaterol o.d. delivered via SDDPI
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/1721
|
0.17%
3/1718
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Acute coronary syndrome
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Acute myocardial infarction
|
0.17%
3/1721
|
0.12%
2/1718
|
|
Cardiac disorders
Angina pectoris
|
0.29%
5/1721
|
0.29%
5/1718
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Aortic valve calcification
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Arrhythmia
|
0.17%
3/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Arrhythmia supraventricular
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Atrial fibrillation
|
0.17%
3/1721
|
0.23%
4/1718
|
|
Cardiac disorders
Atrial flutter
|
0.12%
2/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Atrioventricular block
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Bradycardia
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Bundle branch block left
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Cardiac arrest
|
0.17%
3/1721
|
0.12%
2/1718
|
|
Cardiac disorders
Cardiac failure
|
0.17%
3/1721
|
0.29%
5/1718
|
|
Cardiac disorders
Cardiac failure chronic
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Cardiac failure congestive
|
0.17%
3/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.17%
3/1721
|
0.12%
2/1718
|
|
Cardiac disorders
Cardiomegaly
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Cardiomyopathy
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Congestive cardiomyopathy
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Cor pulmonale
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Coronary artery disease
|
0.06%
1/1721
|
0.17%
3/1718
|
|
Cardiac disorders
Cyanosis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Diastolic dysfunction
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Ischaemic cardiomyopathy
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Left ventricular hypertrophy
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Mitral valve incompetence
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Myocardial infarction
|
0.23%
4/1721
|
0.47%
8/1718
|
|
Cardiac disorders
Myocardial ischaemia
|
0.35%
6/1721
|
0.23%
4/1718
|
|
Cardiac disorders
Palpitations
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Right ventricular failure
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Cardiac disorders
Tachyarrhythmia
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Ear and labyrinth disorders
Hypoacusis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Endocrine disorders
Goitre
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Eye disorders
Angle closure glaucoma
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Eye disorders
Cataract
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Eye disorders
Maculopathy
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Eye disorders
Retinal vein occlusion
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Acute abdomen
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Colitis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/1721
|
0.17%
3/1718
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Constipation
|
0.06%
1/1721
|
0.17%
3/1718
|
|
Gastrointestinal disorders
Diarrhoea
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Diverticulum
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Duodenal fistula
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Duodenitis
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Gastrointestinal disorders
Gastritis
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Ileus
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.17%
3/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Mallory-Weiss syndrome
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Nausea
|
0.12%
2/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/1721
|
0.17%
3/1718
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Gastrointestinal disorders
Regurgitation
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Sigmoiditis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Gastrointestinal disorders
Thrombosis mesenteric vessel
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.12%
2/1721
|
0.06%
1/1718
|
|
Hepatobiliary disorders
Bile duct stone
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Hepatobiliary disorders
Cholangitis acute
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.06%
1/1721
|
0.12%
2/1718
|
|
Hepatobiliary disorders
Gallbladder fistula
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Immune system disorders
Drug hypersensitivity
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Infections and infestations
Anal abscess
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Infections and infestations
Appendicitis perforated
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Bronchitis
|
0.17%
3/1721
|
0.12%
2/1718
|
|
Infections and infestations
Bronchitis bacterial
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Infections and infestations
Bronchopneumonia
|
0.12%
2/1721
|
0.17%
3/1718
|
|
Infections and infestations
Clostridial infection
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Diverticulitis
|
0.06%
1/1721
|
0.12%
2/1718
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Infections and infestations
H1N1 influenza
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Infections and infestations
Helicobacter infection
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Herpes zoster
|
0.06%
1/1721
|
0.23%
4/1718
|
|
Infections and infestations
Influenza
|
0.23%
4/1721
|
0.12%
2/1718
|
|
Infections and infestations
Intervertebral discitis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Lobar pneumonia
|
0.23%
4/1721
|
0.23%
4/1718
|
|
Infections and infestations
Lower respiratory tract infection
|
1.6%
28/1721
|
1.0%
18/1718
|
|
Infections and infestations
Lower respiratory tract infection bacterial
|
0.23%
4/1721
|
0.12%
2/1718
|
|
Infections and infestations
Lower respiratory tract infection viral
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Lung abscess
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Lung infection
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Infections and infestations
Meningitis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Meningitis viral
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Nasopharyngitis
|
0.17%
3/1721
|
0.17%
3/1718
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Pneumococcal sepsis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Infections and infestations
Pneumonia
|
1.7%
29/1721
|
1.4%
24/1718
|
|
Infections and infestations
Pneumonia bacterial
|
0.06%
1/1721
|
0.12%
2/1718
|
|
Infections and infestations
Pneumonia pneumococcal
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Infections and infestations
Pneumonia staphylococcal
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Pseudomonas infection
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Respiratory tract infection bacterial
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Respiratory tract infection viral
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Infections and infestations
Sepsis
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Infections and infestations
Septic shock
|
0.06%
1/1721
|
0.17%
3/1718
|
|
Infections and infestations
Sinusitis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Infections and infestations
Testicular abscess
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Tracheobronchitis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Infections and infestations
Upper respiratory tract infection
|
0.17%
3/1721
|
0.12%
2/1718
|
|
Infections and infestations
Upper respiratory tract infection bacterial
|
1.0%
18/1721
|
0.93%
16/1718
|
|
Infections and infestations
Urinary tract infection
|
0.06%
1/1721
|
0.12%
2/1718
|
|
Infections and infestations
Urosepsis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Infections and infestations
Viral sepsis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.70%
12/1721
|
0.64%
11/1718
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Injury, poisoning and procedural complications
Concussion
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Injury, poisoning and procedural complications
Fall
|
0.12%
2/1721
|
0.06%
1/1718
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.06%
1/1721
|
0.12%
2/1718
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Injury, poisoning and procedural complications
Penetrating abdominal trauma
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Injury, poisoning and procedural complications
Post procedural fistula
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.12%
2/1721
|
0.06%
1/1718
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Injury, poisoning and procedural complications
Traumatic shock
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Investigations
Arteriogram coronary
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Investigations
C-reactive protein increased
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Investigations
Prostatic specific antigen increased
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.12%
2/1721
|
0.00%
0/1718
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Musculoskeletal and connective tissue disorders
Axillary mass
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.23%
4/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of prostate
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder papilloma
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.12%
2/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.12%
2/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon neoplasm
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gallbladder cancer
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung cancer metastatic
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.23%
4/1721
|
0.29%
5/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to peritoneum
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelofibrosis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm prostate
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.17%
3/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal neoplasm
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Salivary gland adenoma
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Amyotrophic lateral sclerosis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Brain injury
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Cerebral infarction
|
0.12%
2/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Cerebral ischaemia
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Cerebral thrombosis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Cerebrovascular accident
|
0.12%
2/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Coma
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Dizziness
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Grand mal convulsion
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Headache
|
0.12%
2/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Hypoglycaemic coma
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Hypoxic-ischaemic encephalopathy
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Intracranial aneurysm
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Ischaemic stroke
|
0.12%
2/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Lacunar infarction
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Peripheral sensorimotor neuropathy
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Presyncope
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Sensory loss
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Spinal cord compression
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Nervous system disorders
Syncope
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Nervous system disorders
Transient ischaemic attack
|
0.12%
2/1721
|
0.23%
4/1718
|
|
Nervous system disorders
Vascular encephalopathy
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Psychiatric disorders
Completed suicide
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Psychiatric disorders
Confusional state
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Psychiatric disorders
Depression
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Renal and urinary disorders
Bladder neck obstruction
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Renal and urinary disorders
Haematuria
|
0.12%
2/1721
|
0.00%
0/1718
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Renal and urinary disorders
Renal failure
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Renal and urinary disorders
Renal failure acute
|
0.17%
3/1721
|
0.00%
0/1718
|
|
Renal and urinary disorders
Urethral stenosis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Renal and urinary disorders
Urinary retention
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.12%
2/1721
|
0.17%
3/1718
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.23%
4/1721
|
0.12%
2/1718
|
|
Respiratory, thoracic and mediastinal disorders
Apnoea
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
8.5%
147/1721
|
7.0%
121/1718
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.70%
12/1721
|
0.23%
4/1718
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Respiratory, thoracic and mediastinal disorders
Hydrothorax
|
0.00%
0/1721
|
0.12%
2/1718
|
|
Respiratory, thoracic and mediastinal disorders
Hypercapnia
|
0.12%
2/1721
|
0.06%
1/1718
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal oedema
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.12%
2/1721
|
0.12%
2/1718
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.23%
4/1721
|
0.12%
2/1718
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.06%
1/1721
|
0.17%
3/1718
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.12%
2/1721
|
0.00%
0/1718
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory acidosis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.23%
4/1721
|
0.35%
6/1718
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Vascular disorders
Aortic aneurysm
|
0.12%
2/1721
|
0.00%
0/1718
|
|
Vascular disorders
Aortic stenosis
|
0.12%
2/1721
|
0.00%
0/1718
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Vascular disorders
Deep vein thrombosis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Vascular disorders
Hypertension
|
0.12%
2/1721
|
0.06%
1/1718
|
|
Vascular disorders
Hypertensive crisis
|
0.06%
1/1721
|
0.06%
1/1718
|
|
Vascular disorders
Hypertensive emergency
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Vascular disorders
Hypotension
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Vascular disorders
Peripheral artery stenosis
|
0.06%
1/1721
|
0.00%
0/1718
|
|
Vascular disorders
Peripheral ischaemia
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Vascular disorders
Phlebitis
|
0.00%
0/1721
|
0.06%
1/1718
|
|
Vascular disorders
Varicose vein
|
0.00%
0/1721
|
0.06%
1/1718
|
|
General disorders
Chills
|
0.06%
1/1721
|
0.00%
0/1718
|
|
General disorders
Death
|
0.06%
1/1721
|
0.06%
1/1718
|
|
General disorders
Device dislocation
|
0.06%
1/1721
|
0.00%
0/1718
|
|
General disorders
Drug ineffective
|
0.00%
0/1721
|
0.06%
1/1718
|
|
General disorders
Malaise
|
0.06%
1/1721
|
0.00%
0/1718
|
|
General disorders
Multi-organ failure
|
0.00%
0/1721
|
0.06%
1/1718
|
|
General disorders
Non-cardiac chest pain
|
0.23%
4/1721
|
0.06%
1/1718
|
|
General disorders
Oedema due to cardiac disease
|
0.00%
0/1721
|
0.06%
1/1718
|
|
General disorders
Oedema peripheral
|
0.12%
2/1721
|
0.06%
1/1718
|
|
General disorders
Pyrexia
|
0.17%
3/1721
|
0.06%
1/1718
|
|
General disorders
Soft tissue inflammation
|
0.06%
1/1721
|
0.00%
0/1718
|
|
General disorders
Sudden cardiac death
|
0.00%
0/1721
|
0.06%
1/1718
|
|
General disorders
Sudden death
|
0.06%
1/1721
|
0.06%
1/1718
|
Other adverse events
| Measure |
IndIndacaterol
n=1721 participants at risk
Indacaterol 150 μg o.d., delivered via SDDPI o.d. plus placebo to tiotropium o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®)
|
Tiotropium
n=1718 participants at risk
Tiotropium 18 μg o.d. delivered via the manufacturer's proprietary inhalation device (Handihaler®) plus placebo to indacaterol o.d. delivered via SDDPI
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
1.5%
26/1721
|
2.5%
43/1718
|
|
Infections and infestations
Bronchitis
|
2.3%
39/1721
|
2.0%
34/1718
|
|
Infections and infestations
Influenza
|
2.2%
38/1721
|
2.6%
45/1718
|
|
Infections and infestations
Lower respiratory tract infection
|
7.3%
125/1721
|
5.7%
98/1718
|
|
Infections and infestations
Nasopharyngitis
|
6.9%
118/1721
|
5.9%
101/1718
|
|
Infections and infestations
Upper respiratory tract infection
|
4.1%
70/1721
|
3.7%
63/1718
|
|
Infections and infestations
Upper respiratory tract infection bacterial
|
8.1%
139/1721
|
7.4%
127/1718
|
|
Infections and infestations
Urinary tract infection
|
1.8%
31/1721
|
1.5%
26/1718
|
|
Infections and infestations
Viral upper respiratory tract infection
|
5.3%
91/1721
|
3.8%
65/1718
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.3%
39/1721
|
2.3%
40/1718
|
|
Nervous system disorders
Headache
|
3.1%
53/1721
|
2.9%
49/1718
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
38.8%
668/1721
|
34.4%
591/1718
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
107/1721
|
3.3%
56/1718
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.3%
56/1721
|
2.9%
50/1718
|
|
Vascular disorders
Hypertension
|
3.7%
63/1721
|
2.8%
48/1718
|
|
General disorders
Pyrexia
|
1.1%
19/1721
|
1.5%
26/1718
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial.
- Publication restrictions are in place
Restriction type: OTHER