Supplementary appendix

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Supplementary appendix

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2 Contents

Appendix 1: PRISMA checklist ……… 3

Appendix 2: Search strategy ………. 7

Appendix 3: PRISMA flowchart ……… 10

Appendix 4: Characteristics of included studies ………... 11

Appendix 5: Outcomes information of the included studies ……… 16

Appendix 6: Risk of bias assessment ……….. 25

Appendix 7: Evaluation of heterogeneity ………... 29

Appendix 8: Inconsistency analysis ……… 31

Appendix 9: Publication bias assessment ………... 34

Appendix 10: Meta-regression analysis ………. 35

Appendix 11: Confidence in evidence (GRADE assessment) ………...………... 36

Appendix 12: Sensitivity analysis ………... 43

12.1: Removing high risk of bias studies ………...………... 43

12.2: Removing high heterogeneity studies ………….…...……….. 44

Appendix 13: Subgroup analysis ……… 46

13.1: By antibiotics resistance rate …………...……… 46

13.2: By gastric cancer incidence rate ………...………... 51

13.3. By continents …………...……….. 55

Appendix 14: Results of outcome of adverse events leading to treatment discontinuation ……….. 72

References ……….……… 77

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Appendix 1. PRISMA Checklist

PRISMA NMA Checklist of Items to Include When Reporting A Systematic Review Involving a Network Meta-analysis

Section/Topic Item

#

Checklist Item Reported on

Page # TITLE

Title 1 Identify the report as a systematic review incorporating a network meta-analysis (or related form of meta-analysis).

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ABSTRACT Structured summary

2 Provide a structured summary including, as applicable:

Background: main objectives

Methods: data sources; study eligibility criteria, participants, and interventions; study appraisal; and synthesis methods, such as network meta-analysis.

Results: number of studies and participants identified;

summary estimates with corresponding

confidence/credible intervals; treatment rankings may also be discussed. Authors may choose to summarize pairwise comparisons against a chosen treatment included in their analyses for brevity.

Discussion/Conclusions: limitations; conclusions and implications of findings.

Other: primary source of funding; systematic review registration number with registry name.

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INTRODUCTION

Rationale 3 Describe the rationale for the review in the context of what is already known, including mention of why a network meta-analysis has been conducted.

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Objectives 4 Provide an explicit statement of questions being addressed, with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

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METHODS Protocol and registration

5 Indicate whether a review protocol exists and if and where it can be accessed (e.g., Web address); and, if available, provide registration information, including registration number.

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Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years

considered, language, publication status) used as criteria for eligibility, giving rationale. Clearly describe eligible

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treatments included in the treatment network, and note whether any have been clustered or merged into the same node (with justification).

Information sources

7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

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Appendix 2 Search 8 Present full electronic search strategy for at least one

database, including any limits used, such that it could be repeated.

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Appendix 2 Study selection 9 State the process for selecting studies (i.e., screening,

eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

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Data collection process

10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

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Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

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Geometry of the network

S1 Describe methods used to explore the geometry of the treatment network under study and potential biases related to it. This should include how the evidence base has been graphically summarized for presentation, and what characteristics were compiled and used to describe the evidence base to readers.

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Risk of bias within individual studies

12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

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Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means). Also describe the use of additional summary measures assessed, such as treatment rankings and surface under the cumulative ranking curve (SUCRA) values, as well as modified approaches used to present summary findings from meta-analyses.

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Planned methods of analysis

14 Describe the methods of handling data and combining results of studies for each network meta-analysis. This should include, but not be limited to:

• Handling of multi-arm trials;

• Selection of variance structure;

• Selection of prior distributions in Bayesian analyses; and

• Assessment of model fit.

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Assessment of Inconsistency

S2 Describe the statistical methods used to evaluate the agreement of direct and indirect evidence in the treatment network(s) studied. Describe efforts taken to address its presence when found.

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Risk of bias across studies

15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

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Additional analyses 16 Describe methods of additional analyses if done, indicating which were pre-specified. This may include, but not be limited to, the following:

• Sensitivity or subgroup analyses;

• Meta-regression analyses;

• Alternative formulations of the treatment network; and

• Use of alternative prior distributions for Bayesian analyses (if applicable).

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RESULTS†

Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

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Appendix 3 (PRISMA) Presentation of

network structure

S3 Provide a network graph of the included studies to enable visualization of the geometry of the treatment network.

Figure 1 Summary of

network geometry

S4 Provide a brief overview of characteristics of the

treatment network. This may include commentary on the abundance of trials and randomized patients for the different interventions and pairwise comparisons in the network, gaps of evidence in the treatment network, and potential biases reflected by the network structure.

Appendices 12-14

Study

characteristics

18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

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Appendices 4- 5 Risk of bias within

studies

19 Present data on risk of bias of each study and, if available, any outcome level assessment.

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Appendix 6 Results of

individual studies

20 For all outcomes considered (benefits or harms), present, for each study: 1) simple summary data for each

intervention group, and 2) effect estimates and confidence intervals. Modified approaches may be needed to deal with information from larger networks.

Figures 2, 4-9

& Appendix 14

Synthesis of results 21 Present results of each meta-analysis done, including confidence/credible intervals. In larger networks, authors may focus on comparisons versus a particular

comparator (e.g. placebo or standard care), with full findings presented in an appendix. League tables and forest plots may be considered to summarize pairwise comparisons. If additional summary measures were explored (such as treatment rankings), these should also be presented.

Figures 2, 4-9

& Table 3 &

Appendix 14

Exploration for inconsistency

S5 Describe results from investigations of inconsistency.

This may include such information as measures of model fit to compare consistency and inconsistency models, P values from statistical tests, or summary of inconsistency

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Appendix 8

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estimates from different parts of the treatment network.

Risk of bias across studies

22 Present results of any assessment of risk of bias across studies for the evidence base being studied.

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Appendix 9 Results of

additional analyses

23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression analyses, alternative network geometries studied, alternative choice of prior distributions for Bayesian analyses, and so forth).

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Appendices 12-14

DISCUSSION Summary of evidence

24 Summarize the main findings, including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy-makers).

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Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review level (e.g., incomplete retrieval of identified research, reporting bias). Comment on the validity of the assumptions, such as transitivity and consistency. Comment on any concerns regarding network geometry (e.g., avoidance of certain comparisons).

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Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

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FUNDING

Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review. This should also include information regarding whether funding has been received from manufacturers of treatments in the network and/or whether some of the authors are content experts with professional conflicts of interest that could affect use of treatments in the network.

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PICOS = population, intervention, comparators, outcomes, study design.

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Appendix 2: Search strategy

We primarily searched the databases on 23 July 2019, then updated the search results on 1 December 2020.

We have represented our final search strategy and records for the papers published from 1 January 2011 in the following.

PubMed Search strategy:

(treatment[Title/Abstract] OR treatments[Title/Abstract] OR eradication[Title/Abstract] OR eradications[Title/Abstract] OR regimen[Title/Abstract] OR regimens[Title/Abstract] OR therapy[Title/Abstract] OR therapies[Title/Abstract] OR eradicated[Title/Abstract] OR

treated[Title/Abstract] OR therap*[Title/Abstract] OR intervention*[Title/Abstract]) AND (("helicobacter pylori"[Title/Abstract] OR "h. pylori"[Title/Abstract] OR helicobacter[Title/Abstract]) OR

(helicobacter[MeSH Terms])) Total records: 7564

Embase Search strategy:

1. (treatment:ab,ti OR treatments:ab,ti OR eradication:ab,ti OR eradications:ab,ti OR regimen:ab,ti OR regimens:ab,ti OR therapy:ab,ti OR therapies:ab,ti OR eradicated:ab,ti OR treated:ab,ti OR

therap*:ab,ti OR intervention*:ab,ti) AND [embase]/lim

2. ('helicobacter pylori':ab,ti OR 'h. pylori':ab,ti OR helicobacter:ab,ti) AND [embase]/lim 3. #1 AND #2

Total records: 13212

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8 Cochrane - CENTRAL

Search strategy:

1. (treatment OR treatments OR eradication OR eradications OR regimen OR regimens OR therapy OR therapies OR eradicated OR treated OR therap* OR intervention*):ti AND (treatment OR treatments OR eradication OR eradications OR regimen OR regimens OR therapy OR therapies OR eradicated OR treated OR therap* OR intervention*):ab

2. MeSH descriptor: [Helicobacter] explode all trees

3. ("helicobacter pylori" OR "h. pylori" OR helicobacter):ti AND ("helicobacter pylori" OR "h. pylori"

OR helicobacter):ab 4. #2 OR #3

5. #1 AND #4 Total records: 1737

Web of Science Search strategy:

TOPIC: (treatment OR treatments OR eradication OR eradications OR regimen OR regimens OR therapy OR therapies OR eradicated OR treated OR therap* OR intervention*) AND TOPIC:

("helicobacter pylori" OR "h. pylori" OR helicobacter) Total records: 12177

Scopus

Search strategy:

( ( TITLE ( treatment OR treatments OR eradication OR eradications OR regimen OR regimens OR therapy OR therapies OR eradicated OR treated OR therap* OR intervention* ) OR ABS ( treatment OR treatments OR eradication OR eradications OR regimen OR regimens OR therapy OR therapies OR eradicated OR treated OR therap* OR intervention* ) ) ) AND ( ( TITLE (

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"helicobacter pylori" OR "h. pylori" OR helicobacter ) OR ABS ( "helicobacter pylori" OR "h.

pylori" OR helicobacter ) ) ) Total records: 8652

Clinicaltrials.gov Search strategy:

We searched the Clinicaltrials.gov search portal by Helicobacter pylori name as condition in adult population and interventional studies, and 355 records were finally found.

WHO - ICTRP Search strategy:

We searched the ICTRP search portal by Helicobacter pylori name, and 1185 records were finally found.

ISRCTN Search strategy:

We searched the ISRCTN search portal by Helicobacter pylori name, and 34 records were finally found.

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Appendix 3. PRISMA flowchart

Figure 3. PRISMA flowchart

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Appendix 4. Characteristics of included studies

Table 4. Characteristics of the randomized controlled trials included in the systematic review

Continent Country Author Publication year

Total subjects (n)

Mean age (years)

Male/Female (n) Disease Confirmation of infection

Confirmation of eradication

Washout period (w)

Follow-up period (w)

Africa Egypt Farhoud(1) 2020 103 NA NA Dyspepsia R U 4 6

Kenya Sokwala(2) 2012 120 35 49/71 Dyspepsia S S 12 6

Morocco Lahbabi(3) 2013 323 47.3 162/161 Dyspepsia,

Peptic ulcer

U/H/C/R U 4 12

Morocco Lahbabi(4) 2012 62 42.5 52/10 Peptic ulcer H/R U/H 4 12

Morocco Seddik(5) 2013 281 43 163/118 Dyspepsia,

Peptic ulcer

H U 8 4-6

Nigeria Onyekwere(6) 2014 47 43.6 18/29 Dyspepsia,

Peptic ulcer

U/R U NA 4

Tunisia Loghmari(7) 2012 85 40.1 44/41 Peptic ulcer,

Gastritis

R/H H 15 d 6

Asia China Qian(8) 2012 345 45.1 179/166 Dyspepsia R/U U 4 4

China Su(9) 2017 180 43.4 88/92 Dyspepsia H/R/U U 4 4

China Wang(10) 2017 351 51.1 186/165 Chronic

gastritis

H U 8 12

China Wang(11) 2015 298 52.2 142/156 H. pylori

infection

H/U R/U 4 8

China Yang(12) 2015 (a) 284 NA NA Erosive

gastritis, Peptic ulcer

U U 4 4

China Zhou(13) 2016 700 44.2 367/333 Dyspepsia R U 4 4

China Zhou(14) 2014 280 43.5 132/148 Dyspepsia R/C U 4 8-12

China Zhou(15) 2012 140 36.5 NA Peptic ulcer U/R U/R/H 4 4

Hong Kong Liu(16) 2014 357 56.4 155/202 Dyspepsia H/R U 4 8

India Ashokkumar(17) 2017 120 40.4 56/64 Peptic ulcer,

Gastritis

R/H/S R/H NA 6

India Das(18) 2016 68 29.4 61/7 Peptic ulcer R/H R/H NA 12

India Gopal(19) 2013 74 40.4 71/3 Peptic ulcer R/H R/H NA 12

India Javid(20) 2013 272 36.6 167/105 Peptic ulcer R/H R/H 8 4

India Nasa(21) 2013 231 38.5 128/103 Dyspepsia H/R R NA 4

Iran Alhooei(22) 2016 252 47.3 93/159 Peptic ulcer H/R U NA 8

Iran Fakheri(23) 2019 140 46.8 76/64 Peptic ulcer R/H U 4 8

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Iran Hafizi(24) 2017 96 39.3 45/51 Dyspepsia R S NA 4

Iran Hajiani(25) 2018 203 NA NA Dyspepsia U/H/R/S U 4 4

Iran Moradniani(26) 2018 302 NA NA Dyspepsia,

Peptic ulcer

H U NA 6

Iran Masjedizadeh(27) 2015 200 39 NA Peptic ulcer R/H U 4 8

Iran Masjedizadeh(28) 2014 300 40.3 151/149 Dyspepsia,

Peptic ulcer

R/H U 4 4

Iran Metanat(29) 2015 270 45.9 120/150 Peptic ulcer H/R U NA 8

Iran Sherkatolabbasieh (30)

2017 192 40.6 92/100 Dyspepsia H U 4 6

Iran Sardarian(31) 2013 420 42.7 203/217 Peptic ulcer H/R U NA 8

Japan Maruyama(32) 2017 141 59 81/60 Chronic

gastritis

U U NA 8

Japan Murakami(33) 2016 650 54.6 390/260 Peptic ulcer R/C/U U NA ≥4

Japan Nishizawa(34) 2015 124 60.8 51/73 Atrophic

gastritis

U/C U NA 12

Japan Yanai(35) 2012 119 61.5 93/26 Peptic ulcer,

Atrophic gastritis

R/C/H U NA 12

Korea Choi(36) 2012 460 46.8 239/221 Dyspepsia,

Peptic ulcer

U/R/H U/H 4 4

Korea Choi(37) 2011 197 55.6 112/85 H. pylori

infection

R/H U 8 6

Korea Chung(38) 2012 159 49.6 103/56 Peptic ulcer H/C/R U 4 4

Korea Heo(39) 2015 479 57.3 NA H. pylori

infection

R/H/U U NA 4

Korea Heo(40) 2014 348 57.9 216/132 H. pylori

infection

R/H/U U 2 4

Korea Kim(41) 2020 369 54.4 197/172 H. pylori

infection

H/R U 4 >4

Korea Kim(42) 2019 (a) 1137 55 621/516 H. pylori

infection

R/U/H/C U 4 4-6

Korea Kim(43) 2019 (b) 136 58.8 72/64 Peptic ulcer,

Gastritis, Gastric polyps

R/H U NA 4

infection

R/H U NA 4-5

Korea Kim(45) 2016 601 54 361/240 H. pylori

infection

H/R H/R/U 2 4

infection

U/H/R U 4 4

Korea Lee(47) 2020 222 NA Gastritis,

Peptic ulcer

H/R/U U 4 4

Korea Lee(48) 2015 680 56.8 425/255 Gastritis,

Peptic ulcer

H U NA 6

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Korea Lee(49) 2014 226 54 109/117 H. pylori

infection

R/C/U R/C/U NA 4

Korea Lim(50) 2013 164 56.8 88/76 Dyspepsia,

Peptic ulcer

H/R U 4 4

Korea Oh(51) 2014 184 57.1 68/116 Gastritis,

Peptic ulcer

H/R U 4 4

Korea Oh(52) 2012 246 57.5 107/139 Dyspepsia H/R U 4 4

Korea Park(53) 2017 341 53.2 216/125 H. pylori

infection

H/R U/R/H 2 4

Korea Park(54) 2012 326 52.9 174/152 Peptic ulcer U/R/H U 2 4

Kuwait Alboraie(55) 2015 218 43.9 114/104 Dyspepsia H U 4 4

Lebanon Tarhini(56) 2018 60 NA 30/30 Gastritis,

Peptic ulcer

U/H U 4 4

Malaysia Leow(57) 2018 364 55 175/189 H. pylori

infection

R U NA 4

Mongolia Byambajav(58) 2019 270 37.6 109/161 Dyspepsia R/S/H S 4 4

Myanmar Myint(59) 2020 313 55 80/233 H. pylori

infection

S S NA 4

Qatar Ennkaa(60) 2018 206 38.8 111/95 Dyspepsia R S 4 4

Saudi Arabia Alsohaibani(61) 2015 232 46.9 114/118 H. pylori

infection

R/H/C U NA 6

Singapore Ang(62) 2015 462 48.1 254/208 H. pylori

infection

U/R/H U NA 4

Syria Cheha(63) 2018 80 37.9 29/51 H. pylori

infection

H H 4 6

Taiwan Chen(64) 2015 175 53.3 64/111 H. pylori

infection

H/C/R U/R 4 8

Taiwan Hsu(65) 2020 248 55.4 118/130 H. pylori

infection

H/C/R/U H/C/R/U 4 6

Taiwan Hsu(66) 2018 352 54.2 168/184 H. pylori

infection

H/C/R/U H/C/R/U 4 6

Taiwan Hsu(67) 2014 307 55 175/132 Dyspepsia,

Peptic ulcer

H/C/R H/C/R/U 4 6

Taiwan Huang(68) 2012 169 52.6 96/73 Dyspepsia H/R/C U 4 12

Taiwan Liou(69) 2018 620 53.2 327/293 H. pylori

infection

H/R/C/U U NA ≥6

Taiwan Liou(70) 2016 (a) 1620 53.4 801/819 Dyspepsia H/R/C/U U NA 6

Taiwan Liou(71) 2016 (b) 1300 49.3 644/656 H. pylori

infection

U/H/C/R U 4 6

Taiwan Liou(72) 2013 900 53.3 491/409 H. pylori

infection

U/H/C/R U 4 6

Taiwan Tai(73) 2015 200 NA NA Peptic ulcer,

Gastritis

H/R/U R/H 4 8

Taiwan Tsay(74) 2017 330 54 173/157 Peptic ulcer,

Gastritis

R/H/C R/H NA 6

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Taiwan Wu(75) 2017 162 50.5 75/87 Dyspepsia R/H/C U 4 ≥4

Taiwan Wu(76) 2014 147 53.3 72/75 H. pylori

infection

R/H/C U 4 8

Taiwan Yang(77) 2015 (b) 300 53.9 118/182 Chronic

gastritis

U/H/C U 4 4

Thailand Auesomwang(78) 2018 120 54.9 46/74 Dyspepsia R U 8 4

Thailand Prasertpetmanee(7 9)

2013 110 51.8 39/71 Dyspepsia H/R/C/U U 4 4

Turkey Akpinar(80) 2017 194 48.3 52/142 Dyspepsia U/H U/H 4 6

Turkey Demirci(81) 2015 200 41.5 105/95 Dyspepsia R/H U 4 8

Turkey Gungor(82) 2015 200 43.4 82/118 H. pylori

Infection

U/S/R/H U 4 6

Turkey Kahramanoğlu Aksoy(83)

2017 218 46.6 NA Dyspepsia H S 4 4

Turkey Kefeli(84) 2018 340 37.6 178/162 Gastritis H U 8 4

Turkey Kefeli(85) 2016 390 37.1 208/182 Gastritis,

Peptic ulcer

H U NA 6

Turkey Özdil(86) 2011 187 40.8 72/115 H. pylori

infection

H S NA 5

Turkey Ozturk(87) 2017 195 44.9 93/102 Dyspepsia H/R U 6 6-8

Turkey Polat(88) 2012 150 42 82/68 Dyspepsia U/H U 4 6

Turkey Rakici(89) 2014 343 46.6 148/195 H. pylori

infection

H S 10 d 4-6

Turkey Sezikli(90) 2018 210 42.4 90/120 Dyspepsia H/S U 4 4-6

Turkey Yağbasan(91) 2019 70 39.4 23/47 Dyspepsia H/S S NA 4

Vietnam Tuong(92) 2020 491 44.7 205/286 Peptic ulcer,

Dyspepsia

R/U R/U NA 4-8

Europe Europe Malfertheiner(93) 2011 440 48.2 237/203 Dyspepsia U/R/H/C U 4 4-8

Greece Apostolopoulos(9 4)

2020 364 57.8 164/200 Peptic ulcer,

Dyspepsia

U/R/H U/H 4 4

Greece Apostolopoulos(9 5)

2016 364 58.8 193/171 Peptic ulcer,

Dyspepsia

U/R/H U 4 4

Greece Georgopoulos(96) 2016 353 52.1 186/167 Dyspepsia R U 2 4

Greece Georgopoulos(97) 2013 257 46.1 150/107 Dyspepsia,

Peptic ulcer

U/H/R U 8 8

Ireland Haider(98) 2015 86 41.7 31/55 H. pylori

infection

U U 4 8

Italy De Francesco(99) 2018 129 52.6 60/69 Dyspepsia R/H U NA 4-6

Italy De Francesco(100) 2014 330 47.3 138/192 Dyspepsia H/R U 4 4-6

Italy Dore(101) 2011 417 52.5 153/264 Dyspepsia U/H U/H 4 4-6

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Italy Zullo(102) 2019 291 49 122/169 Dyspepsia H U NA 6

Italy Zullo(103) 2013 180 49.7 73/107 Dyspepsia,

Peptic ulcer

H/R U 4 6

Kosovo Telaku(104) 2013 105 40.8 46/59 Dyspepsia H/R/S H/R/S 4 4

Portugal Boal

Carvalho(105)

2017 63 NA NA H. pylori

infection

H U 4 4-6

Romania Arama(106) 2016 78 40.3 28/50 Dyspepsia H/R R 24 8

Romania Preda(107) 2017 96 51.3 NA H. pylori

infection

S S NA 4

Russia Veliev(108) 2019 210 43 136/74 Peptic ulcer R/U R/U NA 4

Slovenia Tepeš(109) 2016 356 48.3 154/202 Dyspepsia,

Peptic ulcer

U/R/H U 4 4

Spain Cuadrado-

Lavín(110)

2015 299 44.2 NA H. pylori

infection

U/R/ H U 2 4

Spain Cuadrado-

Lavín(111)

2012 250 43 120/130 H. pylori

infection

H/R U 4 4

Spain McNicholl(112) 2014 338 47.4 133/205 Dyspepsia,

Peptic ulcer

U/H/C/R U/H 4 4

Spain Muñoz-

Gómez(113)

2017 212 51 99/113 H. pylori

infection

H/R S/H/R NA 4

Spain & Italy Molina- Infante(114)

2013 343 48.5 169/174 Dyspepsia,

Peptic ulcer

U/H/R/C U 4 8

North America

Canada Fallone(115) 2013 314 60.5 132/182 H. pylori

infection

H/U H/U NA 4

Canada Morse(116) 2013 104 40 51/53 H. pylori

infection

U/H U NA ≥10

USA Eisig(117) 2015 100 47.2 28/72 Dyspepsia H/R U/H/R 4 8

South America

Colombia Castaño

Llano(118)

2013 317 48.3 100/217 H. pylori

infection

H U 4 4

Colombia Castaño

Llano(119)

2012 293 48.2 97/196 H. pylori

infection

H U 4 4

Colombia Gómez

Zuleta(120)

2011 165 NA 60/105 Dyspepsia H H 12 6-8

Cuba Alonso Soto(121) 2016 160 46.1 72/88 H. pylori

infection

H/R H/R 4 4

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Appendix 5. Outcomes information of the included studies

Table 5. Information of primary and secondary outcomes of the randomized controlled trials included in the systematic review

Continent Country Study Therapeutic regimen (N:

Number of subjects)

Eradication rate (ITT, %)

Adverse events leading to treatment discontinuation

Number Name

Africa Egypt

Farhoud, 2020 CCT-14 (N = 34) 55.9 1 Not specified

SCT-10 (N = 34) 79.4 0

SCT-14 (N = 35) 82.9 1 Penicillin allergy

Kenya

Sokwala, 2012 CCT-7 (N = 60) 76.7 NA

CCT-14 (N = 60) 73.3 NA

Morocco

Lahbabi, 2013 CMT-7 (N = 104) 70.2 7 Not specified

CCT-7 (N = 115) 78.3 5 Not specified

SCT-10 (N = 104) 94.2 0

Morocco

Lahbabi, 2012 CCT-7 (N = 30) 66.7 NA

CMT-7 (N = 32) 53.1 NA

Morocco

Seddik, 2013 CCT-7 (N = 141) 66 1 Not specified

SCT-10 (N = 140) 82.9 2 Not specified

Nigeria

Onyekwere, 2014 CCT-7 (N = 18) 88.9 NA

CCT-10 (N = 29) 86.2 NA

Tunisia

Loghmari, 2012 CCT-7 (N = 46) 69.6 NA

CMT-7 (N = 39) 48.7 NA

Asia

China

Qian, 2012 CLT-7 (N = 114) 78.1 0

SCT-10 (N = 115) 78.3 1 Palpitation

SLT-10 (N = 116) 82.8 1 Skin rash

China

Su, 2017 CLT-7 (N = 90) 75.6 1 Not specified

mCBQ-7 (N = 90) 72.2 4 Not specified

China

Wang, 2017 CCT-10 (N = 185) 58.4 4 Not specified

China

Wang, 2015 CCT-7 (N = 143) 55.9 6 Not specified

China Yang, 2015 (a) CCQ-7 (N = 72) 80.6 NA

mCBQ-7 (N = 70) 78.6 NA

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CCQ-14 (N = 71) 93 NA

mCBQ-14 (N = 71) 91.5 NA

China

Zhou, 2016 mCBQ-10 (N = 350) 77.4 7 Not specified

CCQ-10 (N = 350) 78.3 12 Not specified

China

Zhou, 2014 CCT-10 (N = 140) 66.4 NA

SCT-10 (N = 140) 72.1 NA

China

Zhou, 2012 SCT-10 (N = 70) 84.3 NA

CCT-10 (N = 70) 74.3 NA

Hong Kong Liu, 2014 SCT-10 (N = 179) 89.4 NA

CBQ-10 (N = 178) 92.7 NA

India

Ashokkumar, 2017 HCQ-14 (N = 60) 88.3 NA

SCT-10 (N = 60) 73.3 NA

India

Das, 2016 SCT-10 (N = 35) 71.4 NA

CCQ-10 (N = 33) 81.8 NA

India

Gopal, 2013 CCT-10 (N = 39) 69.2 NA

CLT-10 (N = 35) 80 NA

India

Javid, 2013 CCT-10 (N = 134) 61.9 1 Uncontrolled diarrhea

SCT-10 (N = 138) 76.1 0

India

Nasa, 2013 CCT-14 (N = 120) 79.2 NA

SCT-10 (N = 111) 88.3 NA

Iran

Alhooei, 2016 HCQ-14 (N = 126) 87.3 3 Not specified

CCQ-10 (N = 126) 81 4 Not specified

Iran

Fakheri, 2019 CCT-10 (N = 70) 75.7 3 Not specified

CLT-10 (N = 70) 58.6 3 Not specified

Iran

Hafizi, 2017 CCT-10 (N = 47) 66 1 Nausea

SLT-10 (N = 49) 67.3 1 Cramps

Iran

Hajiani, 2018 SLT-10 (N = 112) 54.5 NA

mCBQ-14 (N = 91) 71.4 NA

Iran

Moradniani, 2018 SCT-14 (N = 101) 74.3 1 Not specified

SLT-14 (N = 101) 85.1 2 Not specified

CCT-14 (N = 100) 66 0

Iran Masjedizadeh, 2015 CCT-10 (N = 100) 92 1 Not specified

CBQ-14 (N = 100) 76 0

Iran Masjedizadeh, 2014 SCT-10 (N = 150) 84 5 Not specified

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18

CBQ-14 (N = 150) 79.3 5 Not specified

Iran

Metanat, 2015 HCQ-10 (N = 134) 77.6 4 Not specified

HCQ-14 (N = 136) 86 5 Not specified

Iran

Sherkatolabbasieh, 2017 CCT-14 (N = 95) 68.4 NA

SLT-14 (N = 97) 87.6 NA

Iran Sardarian, 2013 HCQ-14 (N = 210) 89.5 3 Epigastric pain=2; epigastric pain,

nausea, vomiting and bitter taste=1

SCT-10 (N = 210) 76.7 1 Severe vomiting and bitter taste=1 Japan

Maruyama, 2017 CVT-7 (N = 72) 95.8 NA

CCT-7 (N = 69) 69.6 NA

Japan

Murakami, 2016 CVT-7 (N = 329) 91.2 3 Not specified

Japan

Nishizawa, 2015 CCT-7 (N = 60) 73.3 1 Severe diarrhea

CMT-7 (N = 64) 90.6 1 Severe skin rash

Japan

Yanai, 2012 CCQ-7 (N = 59) 94.9 0

CCT-7 (N = 60) 68.3 1 Severe diarrhea

Korea

Choi, 2012 CCT-7 (N = 115) 70.4 NA

CCT-10 (N = 115) 74.8 NA

CCT-14 (N = 115) 80 NA

SCT-10 (N = 115) 75.7 NA

Korea

Choi, 2011 CCT-7 (N = 99) 77.8 5 Not specified

CLT-7 (N = 98) 65.3 3 Not specified

Korea

Chung, 2012 CCT-10 (N = 80) 58.8 3 Not specified

Korea

Heo, 2015 CCQ-10 (N = 238) 78.6 7 Diarrhea=3; nausea=1;

regurgitation=2; headache=1

HCQ-10 (N = 241) 78.8 0

Korea

Heo, 2014 CCQ-10 (N = 174) 78.7 1 Severe nausea

CCT-10 (N = 174) 70.7 2 Neutropenia=1; severe diarrhea=1 Korea

Kim, 2020 CCT-7 (N = 178) 64 2 Abdominal pain

CCT-14 (N = 191) 66 0

Korea

Kim, 2019 (a) CCT-7 (N = 377) 63.9 16 Not specified

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19 Korea

Kim, 2019 (b) CBQ-14 (N = 68) 88.2 NA

CCQ-14 (N = 68) 79.4 NA

Korea

Kim, 2017 CCQ-10 (N = 243) 81.9 NA

SCT-10 (N = 235) 76.6 NA

Korea

Kim, 2016 CCT-7 (N = 295) 70.8 NA

SCT-10 (N = 306) 82.4 NA

Korea

Kim, 2011 SCT-10 (N = 205) 85.9 NA

CCT-14 (N = 204) 75 NA

Korea

Lee, 2020 CCT-7 (N = 111) 64.9 NA

CCT-10 (N = 111) 75.7 NA

Korea

Lee, 2015 CCT-7 (N = 170) 64.1 NA

CMT-7 (N = 170) 68.8 NA

SCT-10 (N = 170) 70 NA

CCQ-7 (N = 170) 79.4 NA

Korea

Lee, 2014 CCT-7 (N = 115) 64.3 0

Korea

Lim, 2013 SCT-14 (N = 86) 75.6 NA

CCQ-14 (N = 78) 80.8 NA

Korea

Oh, 2014 HCQ-14 (N = 90) 81.1 3 Not specified

Korea

Oh, 2012 SCT-10 (N = 116) 79.3 NA

CCT-7 (N = 130) 63.1 NA

Korea

Park, 2017 SCT-10 (N = 85) 77.6 NA

SCT-14 (N = 84) 73.8 NA

CCQ-10 (N = 86) 75.6 NA

CCQ-14 (N = 86) 77.9 NA

Korea

Park, 2012 SCT-10 (N = 162) 77.8 1 Skin rash and diarrhea

CCT-7 (N = 164) 62.2 1 Diarrhea and headache

Kuwait

Alboraie, 2015 CCT-10 (N = 118) 68.6 NA

CBQ-10 (N = 100) 88 NA

Lebanon

Tarhini, 2018 CBQ-10 (N = 30) 50 NA

SCT-14 (N = 30) 80 NA

Malaysia

Leow, 2018 CCT-7 (N = 121) 79.3 NA

mCBQ-7 (N = 120) 81.7 NA

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20

CCT-14 (N = 123) 88.6 NA

Mongolia

Byambajav, 2019 CCT-10 (N = 90) 71.1 0

Myanmar

Myint, 2020 CCQ-14 (N = 156) 78.8 NA

SCT-10 (N = 157) 81.5 NA

Qatar

Ennkaa, 2018 CCT-10 (N = 62) 45.2 NA

CCT-14 (N = 73) 54.8 NA

SCT-10 (N = 71) 50.7 NA

Saudi Arabia

Alsohaibani, 2015 SCT-10 (N = 115) 50.4 NA

CCT-14 (N = 117) 59 NA

Singapore

Ang, 2015 CCT-10 (N = 155) 83.2 NA

SCT-10 (N = 154) 84.4 NA

CCQ-10 (N = 153) 81.7 NA

Syria

Cheha, 2018 CCT-14 (N = 40) 32.5 NA

CLT-14 (N = 40) 27.5 NA

Taiwan

Chen, 2015 HCQ-14 (N = 88) 92 2 Nausea=1; headache=1

SCT-10 (N = 87) 78.2 2 Diarrhea=1; headache=1

Taiwan

Hsu, 2020 RCQ-14 (N = 124) 95.2 8 Diarrhea=3; nausea=1; abdominal

pain=1; headache=1; fever=1; skin rash=1

CCQ-14 (N = 124) 93.5 15 Diarrhea=3; nausea=1; abdominal pain=4; taste perversion=1; cold

sweating=1; skin rash=5 Taiwan

Hsu, 2018 RCQ-14 (N = 176) 96.6 8 Not specified

CBQ-14 (N = 176) 96 10 Not specified

Taiwan

Hsu, 2014 CCT-7 (N = 103) 81.6 1 Palpitation and constipation

CCQ-7 (N = 102) 94.1 1 Abdominal pain and headache

SCT-10 (N = 102) 89.2 1 Constipation

Taiwan

Huang, 2012 SCT-10 (N = 85) 80 1 Drug related acute

rhabdomyolysis

CCQ-10 (N = 84) 88.1 6 Dizziness=5; diarrhea=1

Taiwan

Liou, 2018 SCT-14 (N = 310) 91.3 7 Not specified

Taiwan Liou, 2016 (a) CCT-14 (N = 540) 83.7 19 Not specified

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21

Taiwan

Liou, 2016 (b) SCT-10 (N = 650) 87.2 NA

CCT-14 (N = 650) 85.7 NA

Taiwan

Liou, 2013 SCT-14 (N = 300) 90.7 NA

SCT-10 (N = 300) 87 NA

CCT-14 (N = 300) 82.3 NA

Taiwan

Tai, 2015 CCQ-7 (N = 100) 88 NA

CCT-7 (N = 100) 73 NA

Taiwan

Tsay, 2017 CBQ-14 (N = 164) 93.9 10 Nausea=4, dizziness=2, skin

rash=2, headache=1, diarrhea=1

HCQ-14 (N = 166) 92.8 4 Dizziness=1, headache=1,

diarrhea=1, skin rash=1 Taiwan

Wu, 2017 CCT-7 (N = 81) 72.8 NA

mCBQ-7 (N = 81) 77.8 NA

Taiwan

Wu, 2014 HCQ-10 (N = 77) 81.8 NA

HCQ-14 (N = 70) 85.7 NA

Taiwan

Yang, 2015 (b) SCT-10 (N = 150) 85.3 NA

CCT-7 (N = 150) 80.7 NA

Thailand

Auesomwang, 2018 CCT-10 (N = 60) 80 1 Not specified

SCT-10 (N = 60) 85 4 Not specified

Thailand

Prasertpetmanee, 2013 CCT-7 (N = 55) 92.7 NA

CCT-14 (N = 55) 100 NA

Turkey

Akpinar, 2017 SCT-10 (N = 104) 53.8 3 Not specified

Turkey

Demirci, 2015 CCT-14 (N = 100) 63 NA

mCBQ-14 (N = 100) 72 NA

Turkey

Gungor, 2015 CCT-14 (N = 100) 42 2 Not specified

CBQ-14 (N = 100) 62 3 Not specified

Turkey

Kahramanoğlu Aksoy, 2017 CBQ-14 (N = 111) 88.3 NA

CLT-14 (N = 107) 74.8 NA

Turkey

Kefeli, 2018 HCQ-14 (N = 170) 86.5 6 Not specified

Turkey

Kefeli, 2016 CBQ-10 (N = 130) 87.7 NA

SCT-10 (N = 130) 86.9 NA