Prospective, randomized, and active controlled study of the efficacy of alginic acid and antacid in the treatment of patients with endoscopy-negative reflux disease

Table 1 Demographics between groups- (safety populations)

	All (134)	Topaal （-69）	Nacid （-65）	P
Sex
Male:Female	36:98	25:44	11:54	0.01861
Age (yr)	41.9  ±  13.4	41.6  ±  14.8	42.4  ±  11.8	0.73002
Body mass index(kg/m2)	23.1  ±  3.8	23.4  ±  3.8	22.8 ± 3.8	0.35472
Pulse rate (bpm)	75.2   ±  6.8	75.3  ±  7.0	75.1 ± 6.7	0.90752
SBP (mmHg)	117.0  ±  14.1	119.7  ±  14.2	114.1  ±  13.5	0.02112
DBP (mmHg)	75.0  ±  1.01	76.6  ±  9.5	73.2  ±  10.6	0.05162
History of heartburn (%)				0.96583
6–12 mo	75 (56.4)	39 (56.5)	36 (56.3)
1–5 yr	45 (33.8)	23 (33.3)	22 (34.4)
> 5 yr	13 (9.8)	7 (10.1)	6 (9.4)
Smoking (%)				0.40111
Yes	14 (10.5)	9 (13.0)	5 (7.7)
No	120 (89.5)	60 (87.0)	60 (92.3)
Drinking (%)				1.00001
Yes	5 (3.7)	3 (4.4)	2 (3.1)
No	129 (96.3)	66 (95.6)	63 (96.9)
Coffee (%)				0.08811
Yes	28 (20.9)	10 (14.5)	18 (27.7)
No	106 (79.1)	59 (85.5)	47 (72.3)
VAS (cm)				0.83882
Heartburn	7.5  ±  3.4	7.6  ±  3.0	7.4  ±  3.7
Regurgitation	8.2  ±  3.0	8.1  ±  3.1	8.2  ±  2.9
Dysphagia	1.7  ±  3.2	1.4  ±  3.0	2.0  ±  3.5
Epigastric pain	5.4  ±  4.1	4.6  ±  4.1	6.2  ±  3.9
Nausea	3.5  ±  3.8	3.3  ±  3.8	3.7  ±  3.8
Vomiting	1.1  ±  2.7	1.2  ±  2.7	1.0  ±  2.6
Belching	6.2  ±  4.0	5.9  ±  3.9	6.4  ±  4.1
Quality of life (%)				0.84893
Mild symptoms	4 (3.0)	3 (4.4)	1 (1.5)
Moderate w/o interfering	33 (24.6)	15 (21.7)	18 (27.7)
Moderate with interfering	66 (49.3)	36 (52.2)	30 (46.2)
Symptom as bad/worse	31 (23.1)	15 (21.7)	16 (24.6)

¹Fisher’s exact test; ²ANOVA model; ³Mantel–Henszel test; VAS: visual analog scale.

Table 2 The change in the VAS of heartburn (ITT population)

Unit: cm	Topaal Mean (SE)	Nacid Mean (SE)	Difference	P
Visit 1/baseline Observed data	7.52 (0.42)	7.43 (0.45)	0.09	0.8774
Visit 3/week 7Observed data	1.15 (0.30)	3.06 (0.34)	–1.91	< 0.0001
Change from baseline	–6.39 (0.28)	–4.44 (0.31)	–1.95	< 0.0001

ANCOVA model: Dependent variable = (baseline value) + treatment.

Table 3 Summary of the changes in the VAS at 3 weeks (ITT population)

Unit: cm	Topaal (65)		Nacid (56)			P-value
	Mean	(SE)	Mean	(SE)	Difference
Heartburn
Observed data	2.98	0.37	4.43	0.4	–1.44	0.0091
Change from baseline	–4.52	0.31	–3.03	0.34	–1.49	0.0016
Regurgitation
Observed data	3.52	0.37	5.32	0.4	–1.80	0.0012
Change from baseline	–4.55	0.33	–2.84	0.36	–1.72	0.0006
Dysphagia
Observed data	0.65	0.27	1.25	0.29	–0.60	0.1326
Change from baseline	–0.97	0.19	–0.68	0.2	–0.28	0.3138
Epigastric pain
Observed data	2.08	0.42	3.88	0.45	–1.80	0.0039
Change from baseline	–2.93	0.33	–2.10	0.36	–0.84	0.0925
Nausea
Observed data	1.25	0.32	1.89	0.34	–0.65	0.1705
Change from baseline	–2.10	0.25	–1.51	0.27	–0.59	0.1137
Vomiting
Observed data	0.31	0.18	0.61	0.2	–0.30	0.2662
Change from baseline	–0.92	0.12	–0.55	0.13	–0.37	0.0373
Belching
Observed data	2.54	0.4	5.14	0.43	–2.60	＜0.0001
Change from baseline	–3.64	0.32	–1.40	0.34	–2.23	＜0.0001

ANCOVA model: Dependent variable = (baseline value) + treatment.

Table 4 The change in the severity of the reflux symptom

Population: intent-to-treat	Topaal (%)	Overall (%)	Nacid (%)	P-value
Heartburn				0.00191
Change from baseline
–1	4 (3.3)	1 (1.5)	3 (5.4)
0	28 (23.1)	8 (12.3)	20 (35.7)
1	42 (34.7)	21 (32.3)	21 (37.5)
2	30 (24.8)	23 (35.4)	7 (12.5)
3	17 (14.1)	12 (18.5)	5 ( 8.9)
Regurgitation				0.06251
Change from baseline
–1	2 (1.6)	1 (1.5)	1 ( 1.8)
0	30 (24.8)	12 (18.5)	18 (32.1)
1	42 (34.7)	21 (32.3)	21 (37.5)
2	36 (29.8)	21 (32.3)	15 (26.8)
3	11 ( 9.1)	10 (15.4)	1 (1.8)
Dysphagia				0.25591
Change from baseline
–1	4 (3.3)	2 (3.1)	2 (3.8)
0	90 (74.4)	50 (79.6)	40 (71.4)
1	16 (13.2)	5 ( 7.5)	11 ( 19.6)
2	10 ( 8.3)	7 (10.8)	3 ( 5.3)
3	1 ( 0.8)	1 ( 1.5)	0 ( 0.0)
Epigastric pain				0.25171
Change from baseline
–2	3 (2.5)	1 (1.5)	2 (3.8)
–1	4 ( 3.3)	3 ( 4.6)	1 ( 1.8)
0	57 (47.1)	30 (46.2)	27 (48.2)
1	33 (27.3)	15 ( 23.1)	18 ( 32.1)
2	19 (15.7)	11 (16.9)	8 ( 14.3)
3	5 (4.1)	5 (7.7)	0 ( 0.0)
Nausea				0.22101
Change from baseline
–1	1 (0.8)	0 (0.00%)	1 (1.8)
0	70 (57.9)	33 (50.8)	37 (66.1)
1	23 (19.0)	15 (23.1)	8 (14.3)
2	25 (20.7)	15 (23.1)	10 (17.9)
3	2 (1.7)	2 (3.1)	0 (0.0)
Vomiting				0.18881
Change from baseline
–1	1 (0.8)	0 (0.0)	1 (1.8)
0	100 (82.6)	50 (79.6)	50 (81.3)
1	9 (7.4)	6 (9.2)	3 ( 5.4)
2	9 (7.4)	7 (10.8)	2 ( 3.6)
3	2 (1.7)	2 (3.1)	0 ( 0.0)
Belching				0.03661
Change from baseline
–1	8 (6.6)	2 (3.1)	6 (10.7)
0	48 (39.7)	21 (32.3)	27 (48.2)
1	42 (34.7)	25 (38.5)	17 (30.4)
2	19 (15.7)	13 (20.0)	6 (10.7)
3	4 (3.3)	4 ( 6.2)	0 (0.0)

χ2 test.

Table 5 Summary of the change of quality of life

ITT population	Overall (%)	Topaal (%)	Nacid (%)	P-value
Visit 1/baseline
Observed data				0.9298
No symptom	0 (0.0)	0 (0.0)	0 (0.0)
Moderate symptom	4 (3.3)	3 (4.6)	1 (1.8)
Moderate symptom w/o interfering	29 (24.0)	13 (20.0)	16 (28.6)
Moderate symptom with interfering	61 (50.4)	35 (53.9)	26 (46.4)
Symptom as bad/worse	27 (22.3)	14 (21.5)	13 (23.2)
Study end
Observed data				<0.0001
No symptom	24 (19.8)	19 (29.2)	5 (8.9)
Moderate symptom	51 (42.2)	34 (52.3)	17 (30.4)
Moderate symptom w/o interfering	27 (22.3)	8 (12.3)	19 (33.9)
Moderate symptom with interfering	15 (12.4)	3 (4.6)	12 (21.4)
Symptom as bad/worse	4 (3.3)	1 (1.5)	3 (5.4)
Decrease from baseline				<0.0001
–1	1 (0.8)	0 (0.0)	1 (1.8)
0	24 (19.8)	7 (10.8)	17 (30.4)
1	36 (29.8)	16 (24.6)	20 (35.7)
2	36 (29.8)	22 (33.9)	14 (25.0)
3	16 (13.2)	13 (20.0)	3 (5.4)
4	8 (6.6)	7 (10.8)	1 (1.8)

¹Mantel–Henszel χ2 test.