Add-on trimebutine-maleate does not improve tolerability or eradication in bismuth quadruple therapy for Helicobacter pylori

Table 1 Baseline demographic and clinical characteristics, mean ± SD/n (%)

Variable	Control (n = 66)	Trimebutine (n = 66)	P value
Age, years	47.9 ± 11.1	47.8 ± 11.2	0.932
Male sex	40 (60.6)	34 (51.5)	0.381
Body mass index, kg/m2	24.1 ± 3.0	23.8 ± 3.3	0.507
Current smoker	13 (19.7)	16 (24.2)	0.679
Habitual alcohol use	37 (56.1)	38 (57.6)	0.859
Hypertension	9 (13.6)	7 (10.6)	0.791
Diabetes mellitus	3 (4.5)	5 (7.6)	0.718
Dyslipidemia	4 (6.1)	4 (6.1)	> 0.999
Family history of gastric cancer	14 (21.2)	7 (10.6)	0.152

Comparisons used Student t-test for continuous variables and Fisher’s exact test for categorical variables.

Table 2 Treatment-emergent adverse events during 14-day bismuth quadruple therapy, n (%)

Event	Control (n = 66)	Trimebutine (n = 66)	P value
Any adverse event	34 (51.5)	33 (50.0)	> 0.999
Nausea	20 (30.3)	22 (33.3)	0.852
Diarrhea/loose stool	7 (10.6)	13 (19.7)	0.224
Dizziness	5 (7.6)	1 (1.5)	0.208
Dyspepsia/bloating	5 (7.6)	3 (4.5)	0.718
Dysgeusia (bitter/metallic)	3 (4.5)	4 (6.1)	> 0.999
Headache	3 (4.5)	3 (4.5)	> 0.999
Epigastric discomfort/heartburn	3 (4.5)	4 (6.1)	> 0.999
Asthenia/fatigue	4 (6.1)	3 (4.5)	> 0.999
Vomiting	3 (4.5)	1 (1.5)	0.619
Dark stool (bismuth-related)	3 (4.5)	6 (9.1)	0.492
Abdominal pain	1 (1.5)	2 (3.0)	> 0.999
Anorexia	0 (0.0)	1 (1.5)	> 0.999
Treatment discontinuation due to AE	7 (10.6)	7 (10.6)	> 0.999
Serious adverse event	0 (0.0)	0 (0.0)

Patients could report more than one type of adverse event; percentages therefore do not sum to 100. P values from Fisher’s exact test. AE: Adverse event.

Table 3 Medication adherence and eradication outcomes, mean ± SD/n (%)

Outcome	Control (n = 66)	Trimebutine (n = 66)	P value
Mean adherence, %	85.0 ± 33.0	81.6 ± 36.8	0.764
Adherence ≥ 80%	53 (80.3)	52 (78.8)	> 0.999
Completed 14-day regimen	59 (89.4)	59 (89.4)	> 0.999
Lost to follow-up for UBT	9 (13.6)	11 (16.7)	0.809
ITT eradication n/N (%), (95%CI)	50/66 (75.8) (64.2-84.5)	49/66 (74.2) (62.6-83.3)	> 0.999
PP eradication, n/N (%), (95%CI)	50/57 (87.7) (76.8-93.9)	49/55 (89.1) (78.2-94.9)	> 0.999

95% confidence intervals for single proportions calculated by the Wilson method. Continuous variables compared by Mann-Whitney U-test; categorical variables by Fisher’s exact test. CI: Confidence interval; ITT: Intention-to-treat; PP: Per-protocol; UBT: Urea breath test.

Table 4 Adverse-event and discontinuation rates with bismuth quadruple therapy in comparable randomized trials and registry cohorts

Ref.	Setting/population	BQT-treated (n)	Any adverse event (%)	Discontinuation (%)
Present trial (control arm)	Korea, RCT, 14-day classical BQT	66	51.5	10.6
Nyssen et al[10]	Hp-EuReg, 28 countries	Approximately 22000 (any regimen; BQT subset)	Approximately 37 (BQT)	1.3 (whole cohort)1
Olmedo et al[34]	Hp-EuReg, 2013-2021, all BQT	15582	Approximately 30-40	10
Nyssen et al[35]	Hp-EuReg, single-capsule BQT (Pylera), 10-day	Approximately 2100	Approximately 29	1.7
Malfertheiner et al[6]	Europe, RCT, Pylera 10-day	218	Approximately 50	< 2
Liou et al[7]	Taiwan, RCT, 10-day BQT	540	67	10
Kim et al[36]	Korea, RCT, 10-day BQT	175	67.5	23 (dose reduction or discontinuation)
Gisbert et al[39]	Meta-review of Pylera studies	6482 (30 studies)	Approximately 29 (Pylera)/approximately 37 (classical)	Approximately 2

¹The 13% discontinuation rate in Nyssen et al[10] is the overall European Registry on Helicobacter pylori Management cohort value across all regimens; the bismuth quadruple therapy-specific discontinuation rate was not separately reported.

Superscripted numbers after author/year correspond to the reference list. Numbers are shown as reported in the original studies; registry estimates are rounded. BQT: Bismuth quadruple therapy; Hp-EuReg: European Registry on Helicobacter pylori Management; RCT: Randomized controlled trial.