Efficacy and safety of rebamipide/nizatidine in patients with erosive gastritis: A randomized, multicenter, phase 4 study

Table 1 Baseline characteristics

	Rebamipide/nizatidine (n = 130)	Nizatidine (n = 130)	Total (n = 260)	P value
Age (year), mean ± SD	45.96 ± 14.25	44.0 ± 13.54	44.98 ± 13.91	0.296
Sex, male, n (%)	41 (31.54)	50 (38.46)	91 (35.00)	0.242
Height (cm), mean ± SD	163.13 ± 8.19	164.95 ± 7.24	164.04 ± 7.77	0.034
Weight (cm), mean ± SD	63.25 ± 13.65	63.48 ± 12.17	63.36 ± 12.91	0.530
Body mass index (kg/m2), mean ± SD	23.61 ± 3.76	23.21 ± 3.43	23.41 ± 3.60	0.528
Smoking status, n (%)				0.688
No	107 (82.31)	104 (80.00)	211 (81.15)
Past smoker	13 (10.00)	12 (9.23)	25 (9.62)
Current smoker	10 (7.69)	14 (10.77)	24 (9.23)
Alcohol consumption, yes, n (%)				0.494
No	53 (40.77)	44 (33.85)	97 (37.31)
Past	11 (8.46)	11 (8.46)	22 (8.46)
Current	66 (50.77)	75 (57.69)	141 (54.23)
Concurrent disease, yes, n (%)	25 (19.23)	20 (15.38)	45 (17.31)	0.412
Concomitant medication, yes, n (%)	10 (7.69)	15 (11.54)	25 (9.62)	0.293
Gastrointestinal symptom scores, mean ± SD
Total	14.6 ± 10.0	15.0 ± 11.2	14.8 ± 10.6	0.758
Severity	8.5 ± 5.9	8.5 ± 6.5	8.5 ± 6.2	0.968
Frequency	6.1 ± 4.6	6.5 ± 5.0	6.3 ± 4.8	0.524

Table 2 Baseline endoscopic findings in the study patients, n (%)

	Rebamipide/nizatidine (n = 121)	Nizatidine (n = 118)	P value
Erosion			0.784
1 (no erosion)	0 (0)	0 (0)
2 (1-2 erosions)	42 (34.7)	46 (39.0)
3 (3-5 erosions)	43 (35.5)	40 (33.9)
4 (> 5 erosions)	36 (29.8)	32 (27.1)
Edema			0.379
1 (none)	86 (71.1)	90 (76.9)
2 (pale/whiter and slightly accentuated hexagonal area gastric pattern)	35 (28.9)	27 (23.1)
Redness			0.906
1 (none)	35 (28.9)	31 (26.5)
2 (minimal but obvious change)	74 (61.2)	74 (63.2)
3 (conspicuous patchy discoloration)	11 (9.1)	10 (8.5)
4 (color change is beefy-red in intensity)	1 (0.8)	2 (1.7)
Hemorrhage			0.622
1 (none)	86 (71.1)	77 (65.8)
2 (1 hemorrhagic lesion)	15 (12.4)	17 (14.5)
3 (2-5 hemorrhagic lesions)	15 (12.4)	20 (17.1)
4 (> 6 hemorrhagic lesions)	5 (4.1)	3 (2.6)

Table 3 Treatment outcomes, n (%)

	Rebamipide/nizatidine	Nizatidine	P value
FAS
Total number of patients	121	118
Primary outcome
Erosion improvement	75/121 (62.0)	58/118 (49.2)	0.046
Secondary outcome
Erosion cure	62/121 (51.2)	50/118 (42.4)	0.170
Bleeding improvement	26/35 (74.3)	30/40 (75.0)	0.943
Erythema improvement	38/86 (44.2)	43/86 (50.0)	0.445
Edema cure	22/35 (62.9)	19/27 (70.4)	0.535
Symptom improvement	74/121 (61.2)	67/118 (56.8)	0.492
Erosion improvement in symptomatic subjects1	68/108 (63.0)	54/109 (49.5)	0.046
PPS
Total number of patients	110	108
Primary outcome
Erosion improvement	69/110 (62.7)	54/108 (50.0)	0.058
Secondary outcome
Erosion cure	57/110 (51.8)	47/108 (43.5)	0.220
Bleeding improvement	24/33 (72.7)	26/35 (74.3)	0.884
Erythema improvement	33/79 (41.8)	41/80 (51.2)	0.231
Edema cure	20/31 (64.5)	16/23 (69.6)	0.697
Symptom improvement	71/110 (64.5)	61/108 (56.5)	0.223
Erosion improvement in symptomatic subjects1	64/102 (62.8)	51/104 (49.0)	0.048

¹For patients who responded to have symptoms, endoscopic erosion score improved by 50% or more.

Erosion improvement: The endoscopic erosion score improved by 50% or more. Erosion cure: No remaining erosions observed in endoscopy. Bleeding improvement: The endoscopic bleeding score improved by 50% or more in subjects with an initial bleeding score of 2 or higher. Erythema improvement: The endoscopic erythema score improved by 50% or in subjects with an initial erythema score of 2 or higher. Complete resolution of edema: No remaining edema observed in endoscopy. Symptom improvement: Symptom score improved by 50% or more. FAS: Full analysis set; PPS: Per-protocol set.

Table 4 Incidence of adverse drug reactions of the two treatment groups, n (%)

Variables	Rebamipide/nizatidine (n = 128)	Nizatidine (n = 125)
Total	3 (2.34)	2 (1.60)
Gastrointestinal disorders	3 (2.34)	1 (0.80)
Diarrhea	2 (1.56)	0
Dyspepsia	0	1 (0.80)
Epigastric discomfort	1 (0.78)	0
Nausea	1 (0.78)	0
Immune system disorders	0	1 (0.80)
Drug hypersensitivity	0	1 (0.80)
Skin and subcutaneous tissue disorders	0	1 (0.80)
Yellow skin	0	1 (0.80)