Hybrid, sequential and concomitant therapies for Helicobacter pylori eradication: A systematic review and meta-analysis

Table 1 Characteristics of included studies involving hybrid therapy

Ref.	Region	Design	No. of patients	Age, mean or range, yr	Men, %	Hybrid group	Control group	Confirmation of infection	Confirmation of eradication	Follow-up	Jadad score
Hsu et al[10] (2011)	Taiwan	Single-arm	117	54	50	E 40 mg + A 1g, bid, 7d; E 40 mg + A 1g + C 500 mg + M 500 mg, bid, 7d	NA	RUT, UBT, and histology	UBT	8w	NA
Sardarian et al[25] (2012)	Iran	RCT	420	43	48	P 40 mg + A 1g, bid, 7d; P 40 mg + A 1 g + C 500mg + T 500 mg, bid, 7d	Sequential therapy (P 40 mg + A 1g, bid, 5d; P 40 mg + C 500mg + T 500 mg, bid, 5d)	RUT and/or histology	UBT	8w	3
Molina-Infante et al[27] (2013)	Spain, Italy	RCT	343	18-87	49	O 40 mg + A 1g bid, 7d; O 20 mg +A 1 g + C 500 mg + N 500 mg, bid, 7d	Concomitant therapy (O 20 mg + A 1 g + C 500 mg + N 500 mg, bid, 14d)	UBT or any two of RUT, histology, or culture	UBT	8w	3
Zullo et al[6] (2013)	Italy	RCT	270	49	41	O 40 mg + A 1 g bid, 7d; O 20 mg + A 1 g + C 500 mg + T 500 mg, bid, 7d	Concomitant therapy (O 20 mg + A 1 g + C 500 mg + T 500 mg, bid, 5d); sequential therapy (O 20 mg + A 1 g, bid, 5d; O 20 mg + C 500mg + T 500 mg, bid, 5d)	RUT and histology	UBT	6w	3
Oh et al[13] (2014)	Korea	RCT	184	57	37	R 20mg + A 1g bid, 7d; R 20 mg + A 1 g + C 500 mg + M 500 mg, bid, 7d	Sequential therapy (R 20 mg + A 1g, bid, 7d; R 20 mg + M 500 mg, bid, Mo 500 mg, qd, 7d)	RUT or histology	UBT	6w	3
De Francesco et al[12] (2014)	Italy	RCT	440	47	42	O 20 mg + A 1g bid, 7d; O 20 mg + A 1 g + C 500 mg + T 500 mg, bid, 7d	Concomitant therapy (O 20 mg + A 1 g + C 500 mg + M 500 mg + T 500 mg, bid, 5d or 14d); sequential therapy (R 20 mg + A 1 g, bid, 7d; R 20 mg + M 500 mg, bid, Mo 500 mg, qd, 7d)	RUT+histology	UBT	6-8w	2
Wu et al[23] (2014)	Taiwan	RCT	220	53	49	E 20 mg + A 1g bid, 3d; E 20 mg + A 1 g + C 500 mg + M 500 mg, bid, 7d	Hybrid therapy (E 20 mg + A 1g bid, 5d/7d; E 20 mg + A 1 g + C 500 mg + M 500 mg, bid, 7d)	RUT, UBT, histology, or culture	UBT or triple negative (RUT + histology + culture)	8w	3
Cuadrado-Lavin et al[28] (2015)	Spain	RCT	300	44	38	O 20 mg + A 1 g bid, 5d; O 20 mg + A 1 g + C 500 mg + M 500 mg, bid,5d	Concomitant therapy (O 20 mg + A 1g + C 500 mg + M 500 mg, bid, 10d)	RUT, UBT, or histology	UBT	4w	3
Heo et al[29] (2015)	Korea	RCT	422	57	59	E 20 mg + A 1g bid, 5d; E 20 mg + A 1 g + C 500 mg + M 500 mg, bid, 5d	Concomitant therapy (E 20 mg + A 1 g + C 500 mg + M 500 mg, bid, 10d)	Any two of UBT, histology, or RUT	UBT	4w	3
Hwang et al[26] (2015)	Korea	RCT	284	59	46	R 20 mg + A 1g bid, 7d; R 20 mg + A 1g + C 500 mg + M 500 mg, bid, 7d	Sequential therapy (R 20 mg + A 1g, bid, 7d; R 20 mg + M 500 mg, bid, Mo 500 mg, qd, 7d)	UBT, histology, or RUT	UBT	4w	3
Chen et al[11] (2015)	Taiwan	RCT	175	53	37	R 20 mg + A 1g bid, 7d; R 20 mg + A 1 g + C 500 mg + M 500 mg, bid, 7d	Sequential therapy (R 20 mg + A 1g, bid, 5d; R 20 mg + C 500 mg + M 500 mg, bid, 5d)	RUT + histology, culture	RUT + histology or UBT	8w	2
Metanat et al[24] (2015)	Iran	RCT	270	46	44	P 40 mg + A 1g, bid, 5d; P 40 mg + A 1 g + C 500 mg + T 500 mg, bid, 5d	Sequential therapy (P 40 mg + A 1 g, bid, 7d; P 40 mg + A 1 g + C 500 mg + T 500 mg, bid, 7d)	RUT, histology	UBT	8w	2

A: Amoxicillin; C: Clarithromycin; E: Esomeprazole; M: Metronidazole; Mo: Moxifloxacin; N: Nitroimidazole; O: Omeprazole; P: Pantoprazole; R: Rabeprazole; RUT: Rapid urease test; T: Tinidazole; UBT: 13C-urea breath test.

Table 2 Summary of meta-analyses: hybrid therapy vs sequential and concomitant therapy

Outcomes	Studies, n	Hybrid group	Control group	RR (95%CI)	I2	P value for heterogeneity
Hybrid vs sequential
Eradication rate (PP)	6	88.6%	87.8%	1.03 (0.94-1.12)	82.2%	< 0.05
Eradication rate (ITT)	6	84.3%	85.1%	1.00 (0.89-1.12)	85.2%	< 0.05
Compliance rate	5	96.0%	98.0%	0.99 (0.96-1.02)	50.4%	> 0.05
Side effect rate	6	30.3%	28.2%	1.05 (0.86-1.02)	37.8%	> 0.05
Hybrid vs concomitant
Eradication rate (PP)	5	91.3%	92.4%	1.01 (0.96-1.05)	56.1%	< 0.05
Eradication rate (ITT)	5	84.8%	86.7%	0.99 (0.95-1.03)	0	> 0.05
Compliance rate	4	95.8%	93.2%	1.03 (1.00-1.05) 1	0	> 0.05
Side effect rate	4	39.5%	44.2%	0.93 (0.82-1.05)	0	> 0.05

¹Statistically significant results. ITT: Intention-to-treat; PP: Per-protocol.