Management of Cough in Patients with Chronic Obstructive Pulmonary Disease: Results of the Multicenter Randomized Placebo-Controlled Clinical Trial

Figures & data

Figure 1 Flow diagram.

Table 1 Patient Demographic Characteristics

Parameter	Group		Total	Statistics
	Rengalin	Placebo
All Included Patients	N=121	N=117	N=238
Age, years
Mean±SD	63.9±7.9	64.8±8.4	64.3±8.2	t=0.86;
Median	65	66	65	p=0.39
Minimum	44	45	44
Maximum	80	80	80
Q1-Q3	58–69	59–71	58–71
Gender, n (%)
Male	94 (77.7)	94 (80.3)	188 (79.0)	p=0.64
Female	27 (22.3)	23 (19.7)	50 (21.0)
ITT Analysis	N=116	N=113	N=230	Statistics
Age, years
Mean±SD	63.7±8.0	64.7±8.6	64.2±8.3	t=0.92;
Median	65	65	65	p=0.36
Minimum	44	45	44
Maximum	80	80	80
Q1-Q3	58–69	58–71	58–70
Gender, n (%)
Male	90 (77.6)	90 (79.7)	180 (78.6)	p=0.75
Female	26 (22.4)	23 (20.3)	49 (21.4)
PP Analysis	N=112	N=110	N=222	Statistics
Age, years
Mean±SD	63.8±8.1	64.7±8.6	64.2±8.4	t=0.88; p=0.38
Median	65	65	65
Minimum	44	45	44
Maximum	80	80	80
Q1-Q3	58–69	58–71	58–70
Gender, n (%)
Male	86 (76.8)	87 (79.1)	174 (77.9)	p=0.75
Female	26 (23.2)	23 (20.9)	49 (22.1)

Notes: Mean±SD – mean value and its standard deviation. Patients age was analyzed with Stuart’s t-criterion; the result of the null test with Shapiro–Wilk criterion: Rengalin - p=0.2813, Placebo – p=0.0740. Comparison of the groups according to set was performed with the Fisher criterion.

Table 2 Cough Severity and CAT Scores

Parameter	Group		Statistics
	Rengalin	Placebo
All Included Patients	N=121	N=117
Cough severity, Mean±SD (score)	4.2±1.4	4.1±1.4	Z=0.49; p=0.63
CAT, Mean±SD (score)	19.9±6.6	20.2±6.6	Z=0.36; p=0.72
CAT: 0–10 score, number of patients, n (%)	11 (9.1)	8 (6.8)	p=0.87
CAT: 11–20 score, number of patients, n (%)	53 (43.8)	51 (43.6)
CAT: 21–30 score, number of patients, n (%)	51 (42.1)	50 (42.7)
CAT: 31–40 score, number of patients, n (%)	6 (5.0)	8 (6.8)
ITT Analysis	N=116	N=113	Statistics
Cough severity, Mean±SD (score)	4.2±1.4	4.1±1.4	Z=0.23; p=0.82
CAT, Mean±SD (score)	19.9±6.8	20.3±6.6	Z=0.43; p=0.67
CAT: 0–10 score, number of patients, n (%)	11 (9.5)	8 (7.1)	p=0.87
CAT: 11–20 score, number of patients, n (%)	50 (43.1)	49 (43.4)
CAT: 21–30 score, number of patients, n (%)	49 (42.2)	48 (42.5)
CAT: 31–40 score, number of patients, n (%)	6 (5.2)	8 (7.1)
PP Analysis	N=112	N=110	Statistics
Cough severity, Mean±SD (score)	4.2±1.4	4.1±1.4	Z=0.11; p=0.10
CAT, Mean±SD (score)	19.8±6.6	20.3±6.7	Z=0.50; p=0.61
CAT: 0–10 score, number of patients, n (%)	10 (8.9)	8 (7.3)	p=0.69
CAT: 11–20 score, number of patients, n (%)	49 (43.8)	47 (42.7)
CAT: 21–30 score, number of patients, n (%)	49 (43.8)	47 (42.7)
CAT: 31–40 score, number of patients, n (%)	4 (3.5)	8 (7.3)

Notes: Analysis of the mean values was performed with Wilcoxon criterion. For subgroups comparison according to the number of patients Fisher’s criterion was used.

Figure 2 Percentage of patients responsive to treatment. PP analysis data. *p=0.016.

Table 3 Total CAT Score

	ITT Analysis		PP Analysis
	Rengalin (N = 116)	Placebo (N = 113)	Rengalin (N = 112)	Placebo (N = 110)
Total score at baseline
Mean±SD	19.9 ± 6.8	20.3 ± 6.6	19.8 ± 6.6	20.3 ± 6.7
Median	20.0	20.0	20.0	20.5
Q1-Q3	14.5–25.0	16.0–24.0	14.5–25.0	16.0–24.0
[95% CI]	18.6–21.1	19.1–21.6	18.5–21.0	19.1–21.6
Total score after 4 weeks of treatment
Mean±SD	16.6 ± 6.9	17.8 ± 6.8	16.2 ± 6.6	17.8 ± 6.9
Median	16.0	18.0	16.0	18.0
Q1-Q3	11.0–22.0	13.0–22.0	11.0–21.0	13.0–22.0
[95% CI]	15.3–17.8	16.5–19.1	15.0–17.4	16.5–19.1
Δ (between baseline and after 4 weeks)
Mean±SD	3.3 ± 4.2	2.5 ± 4.1	3.6 ± 3.9	2.5 ± 4.2
Median	3.0	2.5	3.0	2.5
Q1-Q3	1.0–5.0	0.0–5.0	1.0–5.5	0.0–5.0
[95% CI]	2.5–4.1	1.8–3.3	2.8–4.3	1.7–3.3
Δ (between Rengalin and Placebo groups)
Mean±SD	0.79 ± 4.16		1.04 ± 4.02
[95% CI]	−0.29–1.87		−0.02–2.11
Statistics	Z = 1.71		Z = 2.04
	P = 0.0870		P = 0.0416

Notes: Analysis was performed using Wilcoxon criterion; the result of the null test with Shapiro Wilk criterion confirming abnormal data distribution: for ITT Rengalin sample p=0.0006, Placebo – p=0.0001; for PP Rengalin sample – p=0.0080, Placebo – p=0.0001. Mean±SD – mean value and its standard deviation. CI – confidence interval. The threshold of the first and third quartiles are shown (Q1-Q3) due to the lack of normal distribution of parameters.

Figure 3 The change of the total CAT score after 4 weeks of treatment. PP analysis data. *p=0.0416.