Efficacy and safety of mixture of ivy leaf extract and coptidis rhizome in the treatment of acute bronchitis: multicenter, randomized, double-blinded, active-controlled, parallel, therapeutic confirmatory clinical trial

Figures & data

Figure 1. Enrolled patients with acute bronchitis. Abbreviations. AGS, investigational drug (Synatura syrup); AGU, comparative drug (Umckamin); FAS, full analysis set; PPS, per-protocol set.

Table 1. Baseline characteristics of randomized patients.

	AGS group (n = 110)	AGU group (n = 110)	Total patients (n = 220)	p-Value
Age, years	39.81 ± 12.07	38.29 ± 11.07	39.05 ± 11.58	0.2189
Sex, male (%)	31 (28.18)	32 (29.09)	63 (28.64)	0.8814
Height, cm	164.47 ± 7.88	164.71 ± 9.06	164.59 ± 8.47	0.8413
Weight, kg	62.06 ± 11.47	62.63 ± 15.73	62.35 ± 13.73	0.5196
Smoking				0.7705
Non-smoker, n (%)	96 (87.27)	93 (84.55)	189 (85.91)
Past smoker, n (%)	6 (5.45)	6 (5.45)	12 (5.45)
Current smoker, n (%)	8 (7.27)	11 (10.00)	19 (8.64)
Duration of acute bronchitis (day)	6.01 ± 3.27	5.89 ± 3.10	5.95 ± 3.18	0.9991
Past medical history, n (%)	20 (18.18)	22 (20.00)	42 (19.09)	0.7315
Comorbidities, n (%)	31 (28.18)	38 (34.55)	69 (31.36)	0.3091
Respiratory, n (%)	3 (2.73)	2 (1.82)
Gastrointestinal, n (%)	4 (3.64)	13 (11.82)
Infection, n (%)	3 (2.73)	11 (10.00)
Cardiovascular, n (%)	9 (8.18)	5 (4.55)
Musculoskeletal, n (%)	6 (5.45)	6 (5.45)
Reproductive, n (%)	4 (3.64)	7 (6.36)
Metabolism, n (%)	4 (3.64)	5 (4.55)
Others, n (%)	8 (7.27)	5 (4.55)
Prior medication within 1 month, n (%)	4 (3.64)	6 (5.45)	10 (4.09)	0.5174
Concomitant medication, n (%)	12 (10.91)	8 (7.27)	20 (9.09)	0.3482

Figure 2. Change of the total bronchitis severity score (BSS) of the AGS and AGU groups from the baseline visit (visit 2) to end of treatment visit (visit 3) in the per-protocol set (A) and full analysis set (B). Abbreviations. BSS, bronchitis severity score; AGS, investigational drug (Synatura syrup); AGU, comparative drug (Umckamin).

Figure 3. Mean difference in the total BSS between visits 2 and 3 in per-protocol analysis. Abbreviation. BSS, bronchitis severity score.

Table 2. Difference in each BSS component of the AGS and AGU groups with treatment.

	Per-protocol set			Full analysis set
	AGS (n = 109)	AGU (n = 107)	p-Value	AGS (n = 110)	AGU (n = 109)	p-Value
Cough	1.86 ± 1.00	1.87 ± 1.02	0.9248	1.85 ± 1.02	1.88 ± 1.02	0.7704
Sputum	1.46 ± 0.95	1.42 ± 0.92	0.858	1.45 ± 0.95	1.43 ± 0.93	0.9901
Rales/rhonchi	0.27 ± 0.56	0.28 ± 0.64	0.814	0.26 ± 0.55	0.28 ± 0.64	0.7863
Chest pain during coughing	0.32 ± 0.54	0.40 ± 0.55	0.1952	0.32 ± 0.54	0.40 ± 0.55	0.1681
Dyspnea	0.19 ± 0.48	0.27 ± 0.54	0.2424	0.19 ± 0.48	0.28 ± 0.54	0.1989

Abbreviations. BSS, bronchitis severity score; AGS, investigational drug (Synatura syrup); AGU, comparative drug (Umckamin).

Table 3. Treatment response rate between visits 2 and 3.

	Per-protocol set			Full analysis set
	AGS (n = 109)	AGU (n = 107)	p-Value	AGS (n = 110)	AGU (n = 109)	p-Value
Total response rate, n (%)	77 (70.64)	83 (77.57)	0.2454	77 (70.00)	85 (77.98)	0.1783
Total BSS < 3, n (%)	76 (69.72)	83 (77.57)	0.1909	76 (69.09)	85 (77.98)	0.136
Δ Total BSS ≥ 7, n (%)	10 (9.17)	8 (7.48)	0.6517	10 (9.09	8 (7.34)	0.637
Total BSS < 3 and δ total BSS ≥ 7, n (%)	9 (8.26)	8 (7.48)	0.8314	9 (8.18)	8 (7.34)	0.8158

Δ total BSS, difference in the total BSS between visits 2 and 3.

Abbreviations. BSS, bronchitis severity score; AGS, investigational drug (Synatura syrup); AGU, comparative drug (Umckamin).

Table 4. Treatment response rate between visits 2 and 3.

	Per-protocol set			Full analysis set
	AGS (n = 109)	AGU (n = 107)	p-Value	AGS (n = 110)	AGU (n = 109)	p-Value
1 (Deterioration), n (%)	3 (2.75)	3 (2.80)	0.3506	3 (2.73)	3 (2.75)	0.3754
2 (No change), n (%)	6 (5.50)	8 (7.48)		7 (6.36)	8 (7.34)
3 (Slight to moderate improvement), n (%)	24 (22.02)	16 (14.95)		24 (21.82)	16 (14.68)
4 (Major improvement), n (%)	40 (36.70)	52 (48.60)		40 (36.36)	53 (48.62)
5 (Complete recovery), n (%)	36 (33.03)	28 (26.17)		36 (32.73)	29 (26.61)
4 + 5, n (%)	76 (69.72)	80 (74.77)	0.4082	76 (69.09)	82 (75.23)	0.311

Abbreviations. AGS, investigational drug (Synatura syrup); AGU, comparative drug (Umckamin).

Table 5. Subjective satisfaction of patients.

	Per-protocol set			Full analysis set
	AGS (n = 109)	AGU (n = 107)	p-Value	AGS (n = 110)	AGU (n = 109)	p-Value
1 (Very dissatisfied), n (%)	1 (0.92)	0 (0.00)	0.4388	1 (0.91)	0 (0.00)	0.5957
2 (Dissatisfied), n (%)	2 (1.83)	6 (5.61)		3 (2.73)	6 (5.50)
3 (Neutral), n (%)	30 (27.52)	24 (22.43)		30 (27.27)	24 (22.02)
4 (Satisfied), n (%)	44 (40.37)	42 (39.25)		44 (40.00)	43 (39.45)
5 (Very satisfied), n (%)	32 (29.36)	35 (32.71)		32 (29.09)	36 (33.03)

Abbreviations. AGS, investigational drug (Synatura syrup); AGU, comparative drug (Umckamin).

Table 6. Adverse events during the clinical trial.

	AGS (n = 110)		AGU (n = 110)		p-Value
	n (%)	Number of events	n (%)	Number of events
Treatment-emergent adverse events	5 (4.55)	5^a	4 (3.64)	7^b	>0.9999
Number of ADRs	5 (4.55)	5^a	2 (1.82)	5^c	0.4455
Number of SAEs	0 (0.00)	0	0 (0.00)	0
AEs led to study discontinuation	0 (0.00)	0	0 (0.00)	0

Abbreviations. ADR, adverse drug reaction; SAE, serious adverse event; AE, adverse event; AGS, investigational drug (Synatura syrup); AGU, comparative drug (Umckamin).

Note: The number of specific adverse events as below, n.

^aDiarrhea, 3; constipation, 1; alanine aminotransferase increased 1.

^bDiarrhea, 3; aspartate aminotransferase increased 1; flank pain 1; myalgia 1; dyspnea 1.

^cDiarrhea, 2; aspartate aminotransferase increased 1; myalgia 1; dyspnea 1.