Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori

Figures & data

Table 1 Studies evaluating the efficacy of non-bismuth quadruple (concomitant) regimen for the treatment of Helicobacter pylori infection

Author	Country	Publication year	Study design	Disease type	Therapy regimen	Days	No of patients	Eradication rate (%) (ITT)	Eradication rate (%) (PP)
Calvet et al^Citation47	Spain	2000	NC	PUD	O 20 mg bid + A 1 g bid + C 500 mg bid + T 500 mg bid	4	56	49/56 (87.5)	49/54 (90.7)
Catalano et al^Citation48	Italy	2000	RCT	PUD	O 40 mg od + A 1 g bid + C 500 mg bid + M 500 mg bid	3	56	50/56 (89.3)	50/54 (92.6)
Chan et al^Citation49,†	China	2001	NC	PUD, NUD, others	O 20 mg bid + A 20 mg/kg tid + C 7.5 mg/kg tid + M 7.5 mg/kg 5 times a day	7	33	31/33 (94)	31/33 (94)
Molina-Infante et al^Citation50	Spain	2011	NC	PUD, NUD, others	PPI bid + A 1 g bid + C 500 mg bid + M 500 mg	10	155	132/55 (85)	132/150 (88)
Nagahara et al^Citation51	Japan	2000	RCT	PUD, NUD	R 10 mg bid + A 750 mg bid + C 200 mg bid + M 250 mg bid	5	55	52/55 (94.5)	52/53 (98.1)
Nagahara et al^Citation52	Japan	2001	RCT	PUD, NUD	R 20 mg bid + A 750 mg bid + C 200 mg bid + M 250 mg bid	5	80	74/80 (92.5)	74/79 (93.7)
Neville et al^Citation53	UK	1999	RCT	PUD, NUD, others	L 30 mg bid + A 1 g bid + C 250 mg bid + M 400 mg bid	5	56	49/56 (87.5)	49/54 (90.7)
Okada et al^Citation34	Japan	1998	RCT	PUD, NUD, others	O 20 mg bid + A 500 mg tid + Ro 150 mg bid + M 250 mg tid	7	90	85/90 (94.4)	85/88 (96.6)
Okada et al^Citation54	Japan	1999	RCT	PUD, NUD, others	O 20 mg bid + A 500 mg tid + Ro 150 mg bid + M 250 mg tid	7	169	155/169 (92)	155/163 (95)
Treiber et al^Citation33	Germany	1998	RCT	PUD, others	O 20 mg bid + A 1 g bid + C 250 mg bid + M 400 mg bid	5	46	42/46 (91.3)	42/44 (95.5)
Treiber et al (a)^Citation55	Germany	2002	RCT	PUD, NUD, others	L 30 mg bid + A 1 g bid + C 250 mg bid + M 400 mg bid	3	80	65/80 (81.2)	65/76 (85.5)
Treiber et al (b)^Citation55	Germany	2002	RCT	PUD, NUD, others	L 30 mg bid + A 1 g bid + C 250 mg bid + M 400 mg bid	5	83	74/83 (89.2)	74/79 (93.7)
Wu et al^Citation56	Taiwan	2010	RCT	PUD, NUD, others	E 40 mg bid + A 1 g bid + C 500 mg bid + M 500 mg bid	10	115	107/115 (93)	107/115 (93)
Greenberg et al^Citation57	Latin America	2011	RCT	PUD, NUD, others	L 30 mg bid + A 1 g bid + C 500 mg bid + M 500 mg bid	5	488	360/489 (73.6)	348/442 (78.7)
Kongchayanun et al (a)^Citation58	Thailand	2011	RCT	NUD	R 20 mg bid + A 1 g bid + C 1 g od + M 500 mg tid	5	50	45/50 (90)	45/50 (90)
Kongchayanun et al (b)^Citation58	Thailand	2011	RCT	NUD	R 20 mg bid + A 1 g bid + C 1 g od + M 500 mg tid	10	50	48/50 (96)	48/50 (96)
Kim et al^Citation59	Korea	2011	RCT	–	L 30 mg bid + A 1 g bid + C 500 mg bid + M 500 mg bid	5	135	123/135 (91.4)	123/135 (91.4)
Toros et al^Citation60	Turkey	2011	NC	NUD	L 30 mg bid + A 1 g bid + C 500 mg bid + M 500 mg tid	14	84	63/84 (75%)	63/84 (75%)
Kwon et al (a)^Citation61	Korea	2011	RCT	–	L 30 mg bid + A 1 g bid + C 500 mg bid + M 500 mg bid	5	48	42/48 (87.5%)	42/48 (87.5%)
Kwon et al (b)^Citation61	Korea	2011	RCT	–	L 30 mg bid + A 1 g bid + C 500 mg bid + M 500 mg bid	7	49	44/49 (89.8%)	44/49 (89.8%)
Moon et al^Citation62	Korea	2011	RCT	–	PPI bid + A 1 g bid + C 500 mg bid + M 500 mg bid	7	53	43/53 (81.1%)	43/53 (81.1%)
Choi et al^Citation63	Korea	2011	NC	–	R 20 mg bid + A 1 g bid + C 500 mg bid + M 500 mg tid	14	38	24/38 (63.2%)	24/38 (63.2%)

Notes: Days of antibiotic treatment.

† Pediatric patients.

Abbreviations: A, amoxicillin; bid, two times a day; C, clarithromycin; E, esomeprazole; ITT, intention-to-treat; L, lansoprazole; M, metronidazole; NC, non-controlled; NUD, non-ulcer disease; O, omeprazole; od, once daily; PP, per-protocol; PPI, proton pump inhibitor (at standard dose); PUD, peptic ulcer disease; R, rabeprazole; Ro, roxithromycin; RCT, randomized controlled trial; T, tinidazole; tid, three times a day.

Table 2 Meta-analysis of efficacy (intention-to-treat) of studies evaluating the concomitant regimen for the treatment of Helicobacter pylori infection

Study or subgroup	Eradication rate	SE	Weight	Eradication rate IV, random, 95% CI	Eradication rate IV, random, 95% CI
Calvet et al^Citation47	0.875	0.044	4.2%	0.88 [0.79, 0.96]
Catalano et al^Citation48	0.893	0.041	4.4%	0.89 [0.81, 0.97]
Chan et al^Citation49	0.939	0.042	4.3%	0.94 [0.86, 1.02]
Choi et al^Citation63	0.632	0.078	2.6%	0.63 [0.48, 0.78]
Greenberg et al^Citation57	0.736	0.02	5.5%	0.74 [0.70, 0.78]
Kim et al^Citation59	0.91	0.024	5.3%	0.91 [0.86, 0.96]
Kongchayanun et al^Citation58	0.9	0.042	4.3%	0.90 [0.82, 0.98]
Kongchayanun et al^Citation58	0.96	0.028	5.1%	0.96 [0.91, 1.01]
Kwon^Citation61	0.875	0.048	4.0%	0.88 [0.78, 0.97]
Kwon^Citation61	0.9	0.043	4.3%	0.90 [0.82, 0.98]
Molina-Infante et al^Citation50	0.864	0.038	4.6%	0.86 [0.79, 0.94]
Moon et al^Citation62	0.81	0.054	3.6%	0.81 [0.71, 0.92]
Nagahara et al^Citation51	0.945	0.031	5.0%	0.94 [0.88, 1.01]
Nagahara et al^Citation52	0.925	0.029	5.1%	0.93 [0.87, 0.98]
Neville et al^Citation53	0.875	0.044	4.2%	0.88 [0.79, 0.96]
Okada et al^Citation34	0.944	0.024	5.3%	0.94 [0.90, 0.99]
Okada et al^Citation54	0.917	0.021	5.5%	0.92 [0.88, 0.96]
Toros et al^Citation60	0.75	0.047	4.0%	0.75 [0.66, 0.84]
Treiber et al^Citation33	0.913	0.042	4.3%	0.91 [0.83, 1.00]
Treiber et al^Citation55	0.813	0.044	4.2%	0.81 [0.73, 0.90]
Treiber et al^Citation55	0.892	0.034	4.8%	0.89 [0.83, 0.96]
Wu et al^Citation56	0.93	0.024	5.3%	0.93 [0.88, 0.98]
Total (95%CI)			100.0%	0.88 [0.85, 0.91]
Heterogeneity: Tau^2 = 0.00; Chi^2 = 107.58, df = 21 (P < 0.00001); I^2 = 80%
Test for overall effect: Z = 53.68 (P < 0.00001)

Abbreviations: CI, confidence interval; IV, inverse variance; SE, standard error.

Table 3 Meta-analysis comparing the efficacy (intention-to-treat) of the concomitant regimen with that of standard triple therapy for the eradication of Helicobacter pylori infection

Study or subgroup	Concomitant events	Total	Standard events	Total	Weight	Peto odds ratio peto, fixed, 95% CI	Year	Peto odds ratio peto, fixed, 95% CI
Treiber et al^Citation33	42	46	38	42	5.7%	1.10 [0.26, 4.69]	1998
Neville et al^Citation53	49	56	33	56	17.3%	4.24 [1.84, 9.74]	1999
Nagahara et al^Citation51	52	55	40	50	9.0%	3.77 [1.19, 12.00]	2000
Catalano et al^Citation48	50	56	45	55	10.8%	1.82 [0.63, 5.23]	2000
Nagahara et al^Citation52	74	80	65	80	14.4%	2.67 [1.07, 6.65]	2001
Moon et al^Citation62	43	53	55	85	21.2%	2.21 [1.04, 4.69]	2011
Kim et al^Citation59	123	135	116	135	21.6%	1.66 [0.79, 3.51]	2011
Total (95% CI)		481		503	100.0%	2.36 [1.67, 3.34]
Total events	433		392
Heterogeneity: Chi^2 = 4.76, df = 6 (P = 0.57); I^2 = 0%
Test for overall effect: Z = 4.85 (P < 0.00001)

Abbreviation: CI, confidence interval.

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