Inhaled indacaterol for the treatment of COPD patients with destroyed lung by tuberculosis and moderate-to-severe airflow limitation: results from the randomized INFINITY study

Figures & data

Figure 1 Study design.

Abbreviation: o.d., once daily.

Figure 2 Patient disposition.

Table 1 Baseline demographic and clinical characteristics

Parameter	Indacaterol 150 µg o.d. (n=68)	Placebo (n=68)
Age, years, mean (SD)	63.9 (10.9)	64.6 (9.2)
Males	45 (66.2)	40 (58.8)
COPD duration, years, mean (SD)	4.2 (4.0)	4.3 (3.7)
Previous COPD-related medication	55 (80.9)	58 (85.3)
COPD exacerbation in previous year
Yes	4 (5.9)	6 (8.8)
No	64 (94.1)	62 (91.2)
Smoking history
Yes	34 (50.0)	36 (52.9)
No	34 (50.0)	32 (47.1)
Smoker’s pack-year, mean (SD)	33.9 (26.9)	27.9 (15.6)
Radiologic findings, n (%)
Lung volume loss	59 (86.8)	56 (82.4)
Bronchovascular distortion	32 (47.1)	31 (45.6)
Fibrosis	42 (61.8)	46 (67.7)
Post-bronchodilator FEV1, L	1.41 (0.40)	1.39 (0.43)
Post-bronchodilator FEV1, % predicted	54.5 (12.4)	54.8 (11.8)
Post-bronchodilator FEV1/FVC, %	54.7 (10.0)	53.2 (10.5)
BDI focal scorea	7.4 (2.0)	7.5 (1.9)
SGRQ-C total scoreb	37.6 (18.2)	40.1 (21.0)

Notes: Data are presented as n (%) unless otherwise stated.

a Three patients from each group had missing values;

b values are from the ITT population.

Abbreviations: BDI, baseline dyspnea index; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; ITT, intent-to-treat; o.d., once daily; SD, standard deviation; SGRQ-C, St George’s Respiratory Questionnaire for COPD.

Table 2 Change from baseline in trough FEV₁ at week 8 (A) and analysis of change from baseline in FEV₁ at week 8 by smoking status and previous use of fixed-dose combination of inhaled β₂-agonist and ICS (B)

	Indacaterol, LS, mean ± SE	Placebo, LS, mean ± SE	Treatment difference, LS, mean (95% CI)	P-value
A
ITT	0.08±0.02	−0.06±0.02	0.14 (0.09, 0.18)	<0.001
PP	0.10±0.02	−0.04±0.02	0.14 (0.09, 0.19)	<0.001
B
Smoking status
ITT
Yes	0.07±0.03	−0.07±0.02	0.14 (0.07, 0.21)	<0.001
No	0.09±0.02	−0.05±0.02	0.14 (0.08, 0.19)	<0.001
PP
Yes	0.11±0.02	−0.05±0.02	0.16 (0.09, 0.23)	<0.001
No	0.10±0.02	−0.03±0.03	0.13 (0.05, 0.20)	0.001
ICS/LABA use
ITT
Yes	0.05±0.03	−0.07±0.03	0.12 (0.03, 0.20)	0.01
No	0.10±0.02	−0.05±0.02	0.15 (0.10, 0.21)	<0.001
PP
Yes	0.08±0.03	−0.04±0.03	0.12 (0.03, 0.20)	0.007
No	0.11±0.02	−0.04±0.02	0.15 (0.09, 0.21)	<0.001

Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 s; ICS, inhaled corticosteroid; ITT, intent-to-treat; LABA, long-acting β₂-agonist; LS, least squares; PP, per protocol; SE, standard error.

Figure 3 Change from baseline in trough FEV₁ at Week 8 (ITT set and PP set).

Notes: Data are presented as LS means. Δ, Treatment difference LS mean.
Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 s; ITT, intent-to-treat; LS, least squares; PP, per protocol; SE, standard error.

Table 3 Change from baseline in TDI focal scores at Week 8 (A) and change from baseline in SGRQ-C scores at Week 8 (B)

	Indacaterol, mean ± SD	Placebo, mean ± SD	Treatment difference, mean (95% CI)	P-value
A
ITT	1.01±2.15	0.23±2.38	0.78 (0.01, 1.56)	0.047
PP	1.14±2.09	0.33±1.30	0.81 (0.08, 1.54)	0.024
B
ITT	−2.69±13.00	−0.33±16.30	−2.35 (−7.39, 2.68)	0.356
PP	−4.34±11.90	0.45±16.57	−4.79 (−10.64, 1.06)	0.118

Abbreviations: CI, confidence interval; ITT, intent-to-treat; PP, per protocol; SD, standard deviation; SGRQ-C, St George’s Respiratory Questionnaire for COPD; TDI, transition dyspnea index.

Figure 4 (A) Proportion of patients with a clinically important improvement from baseline in TDI total score (≥1 point; ITT and PP population). (B) Proportion of patients achieving MCID in St George’s Respiratory Questionnaire score.

Notes: Data for TDI total score are least squares means. *P<0.05 and **P<0.01 versus placebo.
Abbreviations: ITT, intent-to-treat; MCID, minimal clinically important difference; PP, per protocol; TDI, transition dyspnea index.

Table 4 Change from baseline in COPD assessment test scores

	Indacaterol, mean ± SD	Placebo, mean ± SD	Treatment difference, mean (95% CI)	P-value
ITT
Visit 2	15.40±7.31	16.24±9.30	−0.84 (−3.69, 2.00)	0.559
Visit 4a	15.65±8.08	17.89±8.53	−2.25 (−5.09, 0.59)	0.120
Difference (Visit 4 – Visit 2)	0.25±5.90	1.80±7.65	−1.55 (−3.88, 0.78)	0.192
PP
Visit 2	15.37±8.03	16.30±8.72	−0.93 (−4.37, 2.51)	0.592
Visit 4	15.31±8.68	18.63±8.48	−3.31 (−6.85, 0.22)	0.066
Difference (Visit 4 – Visit 2)	−0.06±6.12	2.33±8.22	−2.38 (−5.33, 0.56)	0.121

Note:

a LOCF was used to impute missing values at Visit 4.

Abbreviations: CI, confidence interval; ITT, intent-to-treat; LOCF, last observation carried forward; PP, per protocol; SD, standard deviation.

Table 5 Incidence of frequent adverse events and serious adverse events in treatment groups (safety set)

Parameter	Indacaterol (n=68)	Placebo (n=68)
Patients with any adverse event	20 (29.41)	30 (44.12)
COPD exacerbation	3 (4.4)	6 (8.8)
Upper respiratory tract infection	3 (4.4)	7 (10.3)
Nasopharyngitis	3 (4.4)	4 (5.6)
Hemoptysis	2 (2.9)	1 (1.5)
Cough	1 (1.5)	2 (2.9)
Pyrexia	0	2 (2.9)
Serious adverse events	3 (4.41)	1 (1.47)
Adverse events leading to discontinuation	1 (1.47)	3 (4.41)

Note: Data are presented as n (%).

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table S1 Full list of institutional review boards and ethics committees which approved this study

Site no	Site name	Principal investigator name
1	Seoul National University Hospital	Chul-Gyu Yoo
2	Kyung Hee University Medical Center	Myung-Jae Park
3	Konkuk University Medical Center	Kwang-Ha Yoo
4	Korea University Guro Hospital	Jae Jeong Shim
5	Asan Medical Center	Yeon-Mok Oh
6	Hallym University Sacred Heart Hospital	Ki-Suck Jung
7	Severance Hospital	Young-Sam Kim
8	Yeouido St Mary’s Hospital	Hyoung-Kyu Yoon
9	Kangbuk Samsung Hospital	Seong Yong Lim
10	Gachon University Gil Medical Center	Jeong-Woong Park
11	NHIC Ilsan Hospital	Cheong-Ju Kim
12	Chonbuk National University Hospital	Yong Chul Lee