Supplementary Table 1. Efficacy of concomitant therapy and triple therapy of the individual studies ITT analysis Eradicatio
n rate
No.
eradicated
Total No. of cases
Eradication rate
No.
eradicated
Total No.
of cases
Eradicatio n rate
No.
eradicated
Total No.
of cases
C5 T5(AC) T5(CM)
Neville 1999(1) 88% 49 56 59% 33 56 81% 43 53
Nagahara 2000(2) 94.5% 52 55 80% 40 50
C5 T7(AC) T7(CM)
Nagahara 2001(3) 93% 74 80 81% 65 80
Kim 2013(4) 80.7% 109 135 72.6% 98 135
C5 (AC day1-2, ACM day3-5) T10(AC)
Gatalano 2000(5) 89.3% 50 56 81.8% 45 55
C5 T14(AC)
Greenberg 2011(6) 73.6% 360 489 82.2% 401 488
C7 T7(AC) T7(AM)
Yanai 2012(7) 94.9% 56 59 68.3% 41 60
Hsu 2014(8) 94.1% 96 102 81.6% 84 103
Tai 2015(9) 88% 88 100 73% 73 100
Lee 2015(10) 79.4% 135 170 64.1% 109 170 68.8% 117 170
ITT analysis Eradicatio
n rate
No.
eradicated
Total No. of cases
Eradication rate
No.
eradicated
Total No.
of cases
Eradicatio n rate
No.
eradicated
Total No.
of cases
C7 T7(AC) T7(AM)
Tepes 2016(11) 91.7% 110 120 83.6% 97 116
Kim 2017(12) 89.7% 204 224 78.3% 181 231 82.6% 180 218
C7 T7(AC) T10(AC)
Wang 2014(13) 91.4% 74 81 79.3% 65 82 79.5% 66 83
C7 T14(AC)
Moradniani 2017(14)
80.4% 86 107 66.4% 71 107
C10 T10(AC)
Yasser F 2013(15) 57.1% 44 77 58.1% 36 62
Georgopoulos 2013(16)
90.5% 115 127 73.8% 96 130
Heo 2014(17) 78.7% 137 174 70.7% 123 174
Lim 2014(18) 80% 52 65 59.5% 47 79
Ang 2015(19) 81.7% 125 153 83.2% 129 155
Guadrado-Lavin 2015(20)
90% 107 119 70% 42 60
Chung 2016(21) 77.8% 137 176 62.6% 107 171
ITT analysis Eradicatio
n rate
No.
eradicated
Total No. of cases
Eradication rate
No.
eradicated
Total No.
of cases
Eradicatio n rate
No.
eradicated
Total No.
of cases
C10 T14(AC)
Liou 2016(22) 86% 464 540 84% 452 540
C14 T10(AC)
Mihai 2017(23) 85% 34 40 67.5% 27 40
Abbreviations: ITT, Intention to treat; C5, concomitant therapy for 5 days; C7, concomitant therapy for 7 days; C10, concomitant therapy for 10 days; T5, triple therapy for 5 days; T7, triple therapy for 7 days; T10, triple therapy for 10 days; T14, triple therapy for 14 days; AC: amoxicillin and clarithromycin; CM:
clarithromycin and metronidazole; ACM: amoxicillin, clarithromycin and metronidazole; AM: amoxicillin and metronidazole
Supplementary Table 2. Adverse effects of concomitant therapy and triple therapy of the individual studies Incidence
of AE %
No with AE
Total No Incidence of AE %
No with AE Total No Incidence of AE %
No with AE Total No
C5 T5(AC) T5(CM)
Neville 1999(1) 51% 24 47 31% 15 48 43% 16 37
Nagahara 2000(1) 26.5% 13 49 22% 9 41
C5 T7(AC) T7(CM)
Nagahara 2001(3) 30.7% 23 75 21.6% 16 74
Kim 2013(4) 35.6% 48 135 25.2% 34 135
C5 (ACM day1-2, ACM day3-5) T10(AC)
Gatalano 2000(5) 42.6% 23 54 48.1% 25 52
C5 T14(AC)
Greenberg 2011(6) Unknown Unknown Unknown Unknown Unknown Unknown
C7 T7(AC) T7(AM)
Yanai 2012(7) 42.9% 24 56 38.9% 21 54
Hsu 2014(8) 13.7% 14 102 8.7% 9 103
Tai 2015(9) 30.4% 28 92 16.3 15 92
Lee 2015(10) 43.7% 69 158 56.7% 86 152 52.2% 82 157
Tepes 2016(11) 25.4% 30 118 15.5% 17 110
Incidence of AE %
No with AE
Total No Incidence of AE %
No with AE Total No Incidence of AE %
No with AE Total No
C7 T7(AC) T7(AM)
Kim 2017(12) Unknown Unknown Unknown Unknown Unknown Unknown Unknown Unknown Unknow
n
C7 T7(AC) T10(AC)
Wang 2014(13) 8.8% 7 80 7.5% 6 80 9.8% 8 82
C7 T14(AC)
Moradniani 2017(14)
14.6% 15 103 16.6% 17 103
C10 T10(AC)
Yasser F 2013(15) Unknown Unknown Unknown Unknown Unknown Unknown
Georgopoulos 2013(16)
30.9% 38 123 28.4% 35 123
Heo 2014(17) 38.3% 62 162 34% 55 162
Lim 2014(18) Unknown Unknown Unknown Unknown Unknown Unknown
Ang 2015(19) Unknown Unknown Unknown Unknown Unknown Unknown
Guadrado-Lavin 2015(20)
65.8% 79 120 45% 27 60
Chung 2016(21) 39.2% 69 176 35.1% 60 171
C10 T14(AC)
Liou 2016(22) 58% 309 535 47% 252 535 Incidence
of AE %
No with AE
Total No Incidence of AE %
No with AE Total No Incidence of AE %
No with AE Total No
C14 T10(AC)
Mihai 2017(23) 32.5% 13 40 17.5% 7 40
Abbreviations: ITT, Intention to treat; C5, concomitant therapy for 5 days; C7, concomitant therapy for 7 days; C10, concomitant therapy for 10 days; T5, triple therapy for 5 days; T7, triple therapy for 7 days; T10, triple therapy for 10 days; T14, triple therapy for 14 days; AC: amoxicillin and clarithromycin; CM:
clarithromycin and metronidazole; ACM: amoxicillin, clarithromycin and metronidazole; AM: amoxicillin and metronidazole
Supplementary Table 3. The efficacies of concomitant therapy and triple therapy according to the antibiotic susceptibility patterns
Concomitant therapy Triple therapy
Study Compariso
n C/T
CLA-S, MET- S, % (cured/total
)
CLA-S, MET- R, % (cured/total)
CLA-R, MET-S,
% (cured/total)
CLA-R, MET- R, % (cured/total)
CLA-S, MET-S,
% (cured/total)
CLA-S, MET- R, % (cured/total
)
CLA-R, MET-S,
% (cured/total)
CLA-R, MET- R, % (cured/total
) Hsu 2014(8) C7T7 23/23(100%
)
18/18(100%) 2/2(100%) 2/3(66.7%) 22/24(91.7%) 7/8(87.5%) 2/4(50%) 2/3(66.7%)
Tai 2015(9) C7T7 - - - 1/3(33.3%) - - - 0/6(0%)
Liou 2016(22)
C10T14 189/211(90
%)
61/69(88%) 26/36(72%) 13/22(59%) 186/209(89%) 66/77(86%) 14/29(48%) 7/19(37%)
CLA: clarithromycin; MET: metronidazole; S: susceptible; R: resistant.
Supplementary Table 4. The efficacies of concomitant therapy according to the antibiotic susceptibility patterns in the literature Study
(First author/Year)
Duration (day)
Country Test used for MIC determination
PPI type /dosage
CLA-S, MET-S,
% (cured/total)
CLA-S, MET-R,
% (cured/total)
CLA-R, MET-S, % (cured/total)
CLA-R, MET-R,
% (cured/total)
Okada 1999(24) 7 Japan E-test Omeprazole/20mg 95·2% (11/124) 95·7% (22/23) 100% (12/12) 75% (3/4)
Treiber 2002(25) 3-5 German
y
E-test Lansoprazole/30m g
or
ranitidine/300mg
89·7% (35/39) 50% (6/12) - 50% (2/4)
Wu 2010(26) 10 Taiwan E-test Esomeprazole/40m
g
91·2% (52/57) 95·5% (21/22) - 75% (3/4)
Molina–Infante 2012(27) 10 Spain E-test A standard dose PPI
89% (25/28) 100% (8/8) 100% (5/5) 75% (3/4)
Huang 2012(28) 10 China E-test Lansoprazole/30m
g
90·9% (20/22) 100% (14/14) 100% (1/1) 100% (2/2)
Georgopoulos 2013(29) (first-line)
10 Greece E-test Esomeprazole/40m
g
100% (30/30) 100% (25/25) 87% (13/15) 70% (7/10)
Georgopoulos 2013(29) (second-line)
10 Greece E-test Esomeprazole/40m
g
100% (7/7) 50% (1/2) 80% (4/5) 42% (5/12)
Molina–Infante 2013(30) 14 Spain E-test Omeprazole/40mg 94% (17/18) 100% (8/8) 100% (5/5) 100% (3/3)
Hsu 2014(8) 7 Taiwan E-test Pantoprazole/40m
g
100% (23/23) 100% (18/18) 100% (2/2) 66·7% (2/3)
Tai 2015(9) 7 Taiwan Agar dilution
test
Esomeprazole/40m g
- - - 33.3% (1/3)
Georgopoulos 2016(31) 10 Greece E-test Esomeprazole/40m g
97·1% (67/69) 97·4% (38/39) 89·3% (25/28) 75% (9/12)
Liou 2016(22) 10 Taiwan Agar dilution
test
Lansoprazole/30m g
95·3%
(183/192)
95·2% (59/62) 76·5% (26/34) 63·2% (12/19)
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Figure legends
Supplementary Figure 1.
Funnel plot of concomitant therapy for 7-14 days vs. triple therapy for 7-14 days.1a. Funnel plot on trials comparing the efficacy
1b. Funnel plot on trials comparing the adverse effects
