Consensus statement the Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults
Yüklə 0,75 Mb. Pdf görüntüsü
|
- Bu səhifədəki naviqasiya:
- Document Outline
|
floxacin but not cipro floxacin use. Int J Antimicrob Agents 2010; 35:261 –264
. 89.
Wu HH, Liu HY, Lin YC, et al. Correlation between lev- o floxacin consumption and the incidence of nosocomial infections due to fluoroquinolone-resistant Escherichia coli. J Microbiol Immunol Infect 2012 May 4 [Epub ahead of print] . 90.
May L, Klein EY, Rothman RE, et al. Trends in antibiotic resistance in coagulase-negative staphylococci in the United States, 1999 to 2012. Antimicrob Agents Che- mother 2014;58:1404 –1409 .
Gatta L, Vakil N, Leandro G, et al. Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children. Am J Gastroenterol 2009; 104:3069 –3079; quiz 1080 . 92.
Jafri NS, Hornung CA, Howden CW. Meta-analysis: sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment. Ann Intern Med 2008;148:923 –931 .
Gisbert JP, Calvet X, O ’Connor A, et al. Sequential therapy for Helicobacter pylori eradication: a critical re- view. J Clin Gastroenterol 2010;44:313 –325 .
Nyssen O, McNicholl A, Megraud F, et al. Sequential versus standard triple therapy for Helicobacter pylori eradication (protocol). Cochrane Database Syst Rev 2011:CD009034 . 95.
Nyssen OP, McNicholl AG, Megraud F, et al. Meta- analysis of sequential vs. standard triple therapy for Helicobacter pylori
eradication: final results of a Cochrane systematic review (abstr Su1165). Gastroen- terology 2014;146:S393 . 96.
Kim JS, Park SM, Kim BW. Sequential or concomitant therapy for eradication of H. pylori infection: a systematic review and meta-analysis. J Gastroenterol Hepatol 2015; 30:1338
–1345 . 97. He L, Deng T, Luo H. Meta-analysis of sequential, concomitant and hybrid therapy for Helicobacter pylori eradication. Intern Med 2015;54:703 –710
. 98.
Morse AL, Goodman KJ, Munday R, et al. A randomized controlled trial comparing sequential with triple therapy for Helicobacter pylori in an Aboriginal community in the Canadian North. Can J Gastroenterol 2013;27:701 –706 .
Marin AC, McNicholl AG, Gisbert JP. A review of rescue regimens after clarithromycin-containing triple therapy failure (for Helicobacter pylori eradication). Expert Opin Pharmacother 2013;14:843 –861 .
van der Wouden EJ, Thijs JC, van Zwet AA, et al. The in fluence of in vitro nitroimidazole resistance on the ef- ficacy of nitroimidazole-containing anti-Helicobacter py- lori regimens: a meta-analysis. Am J Gastroenterol 1999; 94:1751 –1759
. 101.
Graham DY, Osato MS, Hoffman J, et al. Metronidazole containing quadruple therapy for infection with metroni- dazole resistant Helicobacter pylori: a prospective study. Aliment Pharmacol Ther 2000;14:745 –750 .
van der Wouden EJ, Thijs JC, Kusters JG, et al. Mech- anism and clinical signi ficance of metronidazole resis- tance in Helicobacter pylori. Scand J Gastroenterol 2001; 36:10 –14
. 103.
Bardhan K, Bayerdorffer E, Veldhuyzen Van Zanten SJ, et al. The HOMER Study: the effect of increasing the dose of metronidazole when given with omeprazole and amoxicillin to cure Helicobacter pylori infection. Heli- cobacter 2000;5:196 –201
. 104.
Roghani HS, Massarrat S, Pahlewanzadeh MR, et al. Effect of two different doses of metronidazole and tetracycline in bismuth triple therapy on eradication of Helicobacter pylori and its resistant strains. Eur J Gas- troenterol Hepatol 1999;11:709 –712
. 105.
Marin AC, McNicholl AG, Gisbert JP. Ef ficacy of a second-line levo floxacin-containing triple therapy after the failure of the non-bismuth sequential or concomitant treatments: systematic review and meta-analysis (abstr P11.39). Helicobacter 2014;19(suppl 1):139 –140
. 106.
Di Caro S, Fini L, Daoud Y, et al. Levo floxacin/
amoxicillin-based schemes vs quadruple therapy for Helicobacter pylori eradication in second-line. World J Gastroenterol 2012;18:5669 –5678
. 107.
Chuah SK, Tai WC, Hsu PI, et al. The ef ficacy of
second-line anti-Helicobacter pylori therapy using an extended 14-day levo floxacin/amoxicillin/proton-pump inhibitor treatment –a pilot study. Helicobacter 2012; 17:374
–381 . 108. Gisbert JP, Romano M, Gravina AG, et al. Helicobacter pylori second-line rescue therapy with levo floxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments. Aliment Pharmacol Ther 2015;41:768 –775 .
Urgesi R, Pelecca G, Cianci R, et al. Helicobacter pylori infection: is sequential therapy superior to standard triple therapy? A single-centre Italian study in treatment-naive July 2016 Toronto Consensus for H pylori Treatment 67
and non-treatment-naive patients. Can J Gastroenterol 2011;25:315 –318 .
Liu KS, Hung IF, Seto WK, et al. Ten day sequential versus 10 day modi fied bismuth quadruple therapy as empirical firstline and secondline treatment for Heli- cobacter pylori in Chinese patients: an open label, randomised, crossover trial. Gut 2014;63:1410 –1415
. 111.
Gisbert JP, Calvet X. Review article: rifabutin in the treatment of refractory Helicobacter pylori infection. Aliment Pharmacol Ther 2012;35:209 –221
. 112.
Gisbert JP, Castro-Fernandez M, Perez-Aisa A, et al. Fourth-line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures. Aliment Pharmacol Ther 2012;35:941 –947 .
Gisbert JP, Castro-Fernandez M, Aisa AP, et al. Fourth- line rescue therapy with rifabutin in patients with three H. pylori eradication failures (abstr Su1131). Gastroenter- ology 2015;148:S-416 . 114.
Van der Poorten D, Katelaris PH. The effectiveness of rifabutin triple therapy for patients with dif ficult-to- eradicate Helicobacter pylori in clinical practice. Aliment Pharmacol Ther 2007;26:1537 –1542
. 115.
Ueki N, Miyake K, Kusunoki M, et al. Impact of quadruple regimen of clarithromycin added to metronidazole- containing triple therapy against Helicobacter pylori infection following clarithromycin-containing triple- therapy failure. Helicobacter 2009;14:91 –99 . 116. Sugimoto M, Furuta T, Shirai N, et al. Evidence that the degree and duration of acid suppression are related to Helicobacter pylori eradication by triple therapy. Heli- cobacter 2007;12:317 –323 .
Vallve M, Vergara M, Gisbert JP, et al. Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis. Aliment Pharmacol Ther 2002;16:1149 –1156 .
Villoria A, Garcia P, Calvet X, et al. Meta-analysis: high- dose proton pump inhibitors vs. standard dose in triple therapy for Helicobacter pylori eradication. Aliment Pharmacol Ther 2008;28:868 –877 .
McNicholl AG, Linares PM, Nyssen OP, et al. Meta- analysis: esomeprazole or rabeprazole vs. first-
generation pump
inhibitors in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther 2012;36:414 –425
. 120.
Maradey-Romero C, Fass R. New and future drug development for gastroesophageal re flux disease. J Neurogastroenterol Motil 2014;20:6 –16
. 121.
Garnock-Jones KP. Vonoprazan: first global approval. Drugs 2015;75:439 –443
. 122.
Scarpignato C, Hunt RH. Editorial: towards extended acid suppression - the search continues. Aliment Phar- macol Ther 2015;42:1027 –1029
. 123.
Hunt R, Scarpignato C. Potassium-competitive acid blockers (P-CABs): Are they finally ready for prime time in acid-related disease? Clin Trans Gastroenterol 2015; 6:e119 .
Murakami K, Sakurai Y, Shiino M, et al. A phase 3, double-blind study of a triple therapy with TAK-438, amoxicillin, and clarithromycin as first line eradication of H. pylori and a triple therapy with TAK-438, amoxicillin, and metronidazole as second line eradication of H. pylori (abstr Tu1056). Gastroenterology 2014;5:S-740 . 125. Chiba N. Chapter 5: Ulcer disease and Helicobacter pylori. In: McDonald J, Burroughs A, Feagan B, eds. Evidence-based gastroenterology and hepatology. 2nd ed. New Delhi: Blackwell Publishing Ltd, 2004:83 –116 .
Wang ZH, Gao QY, Fang JY. Meta-analysis of the ef fi- cacy and safety
of Lactobacillus-containing and Bi
ration in Helicobacter pylori eradication therapy. J Clin Gastroenterol 2013;47:25 –32 .
Manfredi M, Bizzarri B, Sacchero RI, et al. Helicobacter pylori infection in clinical practice: probiotics and a combination of probiotics þ lactoferrin improve compli- ance, but not eradication, in sequential therapy. Heli- cobacter 2012;17:254 –263 .
Shavakhi A, Tabesh E, Yaghoutkar A, et al. The effects of multistrain probiotic compound on bismuth-containing quadruple therapy for Helicobacter pylori infection: a randomized placebo-controlled triple-blind study. Heli- cobacter 2013;18:280 –284
. 129.
Molina-Infante J, Gisbert JP. Probiotics for Helicobacter pylori eradication therapy: not ready for prime time. Rev Esp Enferm Dig 2013;105:441 –444
. 130.
Zhang G, Zou J, Liu F, et al. The ef ficacy of moxifloxacin- based triple therapy in treatment of Helicobacter pylori infection: a systematic review and meta-analysis of ran- domized clinical trials. Braz J Med Biol Res 2013; 46:607
–613 . 131. Wu C, Chen X, Liu J, et al. Moxi floxacin-containing triple therapy versus bismuth-containing quadruple therapy for second-line treatment of Helicobacter pylori infection: a meta-analysis. Helicobacter 2011;16:131 –138
. 132.
Wenzhen Y, Kehu Y, Bin M, et al. Moxi floxacin-based triple therapy versus clarithromycin-based triple therapy for
first-line treatment of Helicobacter pylori infection: a meta-analysis of randomized controlled trials. Intern Med 2009;48:2069 –2076
. 133.
Gisbert JP, Romano M, Molina-Infante J, et al. Two- week, high-dose proton pump inhibitor, moxi floxacin triple Helicobacter pylori therapy after failure of standard triple or non-bismuth quadruple treatments. Dig Liver Dis 2015;47:108 –113 .
Sezgin O, Altintas E, Ucbilek E, et al. Bismuth-based therapies for the first step eradication of Helicobacter pylori. Turk J Gastroenterol 2006;17:90 –93 .
Liang J, Li J, Han Y, et al. Helicobacter pylori eradication with ecabet sodium, omeprazole, amoxicillin, and clari- thromycin versus bismuth, omeprazole, amoxicillin, and clarithromycin quadruple therapy: a randomized, open- label, phase IV trial. Helicobacter 2012;17:458 –465
. 136.
Sun Q, Liang X, Zheng Q, et al. High ef ficacy of 14-day triple therapy-based, bismuth-containing quadruple therapy for initial Helicobacter pylori eradication. Heli- cobacter 2010;15:233 –238 .
Srinarong C, Siramolpiwat S, Wongcha-um A, et al. Improved eradication rate of standard triple therapy by adding bismuth and probiotic supplement for Heli- cobacter pylori treatment in Thailand. Asian Pac J Cancer Prev 2014;15:9909 –9913
. 68 Fallone et al Gastroenterology Vol. 151, No. 1 138. Gisbert JP, Morena F. Systematic review and meta- analysis: levo floxacin-based rescue regimens after Heli- cobacter pylori treatment failure. Aliment Pharmacol Ther 2006;23:35 –44 .
Molina-Infante J, Romano M, Fernandez-Bermejo M, et al. Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in pop- ulations with high rates of antibiotic resistance. Gastro- enterology 2013;145:121 –128.e1
. 140.
Zullo A, Scaccianoce G, De Francesco V, et al. Concomitant, sequential, and hybrid therapy for H. pylori eradication: a pilot study. Clin Res Hepatol Gastroenterol 2013;37:647 –650 .
Address requests for reprints to: Carlo A. Fallone, MD, Division of Gastroenterology, McGill University Health Centre, Royal Victoria Hospital Site, 1001 Decarie Boulevard, Room D5.7154, Montréal, Quebec, Canada H4A 3J1. e-mail: carlo.fallone@mcgill.ca . Acknowledgments The consensus group thanks Paul Sinclair (Canadian Association of Gastroenterology [CAG] representative, administrative and technical support) and Louise Hope and Lesley Marshall (CAG, logistics assistance) as well as Pauline Lavigne and Steven Portelance (unaf filiated), who provided medical writing services supported entirely by funds from CAG and the Canadian Helicobacter Study Group. The steering committee (CAF, NC, SVvZ), GIL, and PM reviewed the literature and drafted the statements. GIL and PM assessed the evidence and provided GRADE evaluations. All members of the CAG Treatment of H pylori Infection Consensus Group voted on the recommendations. The steering committee then drafted the initial manuscript, which was reviewed, revised, and approved by all members of the consensus group and all authors. It was subsequently made available to all CAG members for comments before submission for publication. CAG Statement These consensus statements on the treatment of H pylori infection were developed under the direction of Drs Carlo A. Fallone, Naoki Chiba, and Sander Veldhuyzen van Zanten, in accordance with the policies and procedures of CAG and under the direction of CAG Clinical Affairs. They have been reviewed by the CAG Practice Affairs and Clinical Affairs Committees and the CAG Board of Directors. The consensus statements were developed following a thorough consideration of medical literature and the best available evidence and clinical experience. They represent the consensus of a Canadian and international panel composed of experts on this topic. The consensus aims to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families and can be subject to change as scienti fic knowledge and technology advance and as practice patterns evolve. These consensus statements are not intended to be a substitute for physicians using their individual judgment in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available, and available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case. Con flicts of interest The authors disclose the following: Advisory Board: AbbVie (JPG), Allergan (JPG), Almirall (JPG), AstraZeneca (JPG), Casen Fleet (JPG), Casen Recordati (JPG), Chiesi (JPG), Dr Falk Pharma (JPG), Faes Farma (JPG), Ferring Pharmaceuticals (JPG), Gebro Pharma (JPG), Hospira (JPG), Janssen (JPG), Kern Pharma (JPG), MSD (JPG), Nycomed (JPG), Otsuka Pharmaceuticals (JPG), P
fizer (JPG), Shire Pharmaceuticals (JPG), Takeda (JPG), Vifor Pharma (JPG).
Consultation Fees: AbbVie (JKM, SVvZ), Actavis (CAF), AstraZeneca (JKM), Celltrion (JKM), Cubist (JKM), Ferring Pharmaceuticals (JKM), Forest (JKM), Hospira (JKM), Janssen (CAF, JKM, SVvZ), Procter & Gamble (JKM), Pendopharm (CAF), Shire (JKM, SVvZ), Takeda (CAF, JKM). Educational Support: AstraZeneca (PM). Research Grants/Clinical Trial Funding: AbbVie (JPG), Allergan (JPG), Almirall (JPG), AstraZeneca (JPG), Casen Fleet (JPG), Casen Recordati (JPG), Chiesi (JPG), Dr Falk Pharma (JPG), Faes Farma (JPG), Ferring Pharmaceuticals (JPG), Gebro Pharma (JPG), Hospira (JPG), Janssen (JPG), Kern Pharma (JPG), MSD (JPG), Nycomed (JPG), Otsuka Pharmaceutical (JPG), P fizer (JPG), Shire Pharmaceuticals (JPG), Takeda (JPG), Vifor Pharma (JPG). Speaker ’s Bureau: AbbVie (JPG, JKM), Allergan (JPG), Almirall (JPG), Aptalis (JKM), AstraZeneca (JPG), Casen Fleet (JPG), Casen Recordati (JPG), Chiesi (JPG), Dr. Falk Pharma (JPG), Faes Pharma (JPG), Ferring Pharmaceuticals (JPG, JKM), Forest (JKM), Gebro Pharma (JPG), Hospira (JPG), Janssen (JPG, JKM), Kern Pharma (JPG), MSD (JPG), Nycomed (JPG), Otsuka Pharmaceutical (JPG), P fizer (JPG), Procter & Gamble (JKM), Purdue Pharma (SVvZ), Shire (JPG, JKM), Takeda (JPG, JKM, SVvZ), Warner Chilcott (JKM), Vifor Pharma (JPG). Funding Supported by the Canadian Association of Gastroenterology and the Canadian Helicobacter Study Group, with no external funding sources. July 2016 Toronto Consensus for H pylori Treatment 69
Supplementary Appendix 1. Search Strategies Used for EMBASE, MEDLINE, and CENTRAL 1. pylori.tw. 2. clarithromycin.tw. 3. (amoxicillin or amoxycillin).tw. 4. azithromycin.tw. 5. tetracycline.tw. 6. (roxithromycin or erythromycin).tw. 7. nitroimidazole.tw. 8. metronidazole.tw. 9. tinidazole.tw. 10. ranitidine-bismuth.tw 11. levo
floxacin*.tw. 12. moxi
floxacin*.tw. 13. furazolidone.tw. 14. rifabutin.tw. 15. or/2-14 16. 1 and 15 17. eradicat*.tw. 18. 1 and 17 19. 16 or 18 20. limit 19 to yr ¼2008-2013 21. exp animals/not humans.sh. 22. 20 not 21 23. limit 22 to english language 69.e1
Fallone et al Gastroenterology Vol. 151, No. 1 Supplementary Table 1.Evidence for Statement 1 (In patients with H pylori infection, we recommend a treatment duration of 14 days) Quality assessment Summary of findings
Comments Studies
Risk of bias
Inconsistency Indirectness Imprecision Other
considerations a Quality of evidence Overall
quality of evidence Eradication rates (ITT) (%) Relative effect
(95% CI) Longer
duration Shorter
duration Eradication of H pylori infection (importance of outcome: critical for decision making) PPI-based triple regimens: 14 days vs 7 days 4442
Moderate The quality of evidence is moderate
for PAC but low for PMC 1 SR
28 (45 RCTs) Serious b
None None
None 4442
Moderate 81.9
72.9 NNT: 11
(9 –14)
PPI-based triple regimens: 14 days vs 10 days 1 SR
28 (12 RCTs) Serious b
None None
None 4442
Moderate 84.4
78.5 NNT: 17
(11 –46)
PPI-based triple regimens: 10 days vs 7 days 1 SR
28 (24 RCTs) Serious b
None None
None 4442
Moderate 79.9
75.7 NNT: 21
(15 –38)
PPI-based triple regimens: 14 days vs 10 days vs 7 days Increased ef ficacy
with longer durations of therapy in resistant strains 1 RCT
46 None
None None
Serious None
4442 Moderate
NA NA NA PBMT: 14 days vs 7 days 4222 Very low
Trend favoring 14 or 10 vs 7 days but not
statistically signi
ficant 1 SR
28 (3 RCTs)
Serious b None None Very serious None 4222
Very low 77.9
69.1 Nonsigni
ficant difference PBMT: 14 days vs 10 days 1 SR 28
Serious b None None Very serious None 4222
Very low 91.6
92.6 Nonsigni
ficant difference 1 SR c
data from 51 studies) None Serious
None Serious
None 4222
Very low 78.7
75.6 Nonsigni
ficant difference PBMT: 10 days vs 7 days 1 SR 28
Serious b None None Very serious None 4222
Very low 87.4
81.9 Nonsigni
ficant difference July 2016
Toronto Consensus for H
Treatment 69.e2
Supplementary Table 1. Continued Quality assessment Summary of findings
Comments Studies
Risk of bias
Inconsistency Indirectness Imprecision Other
considerations a Quality of evidence Overall
quality of evidence Eradication rates (ITT) (%) Relative effect
(95% CI) Longer
duration Shorter
duration PAMC
4222 Very low
1 SR 44 (cohort-type data from 15 studies) None None
None Serious
None 4222
Very low 92 (10
days) 89 (5
days) Not statistically signi ficant
1 cohort study 45 Serious None Serious
d None
None 4222
Very low 93.3
(14 days) 86.6 (10
days) P
Relative effect not reported PAL: 14 days vs 7 days 4222
Very low 1 SR
28 (2 RCTs)
Serious e None Serious f Serious None 4222
Very low 78.5 (14
days) 42 (7
days) NNT: 3
(2 –10)
SR, systematic review; NA, not applicable. a Including publication bias. b Most of the included RCTs were at high risk or unclear risk of bias. c Unpublished data; SR conducted for the meeting. d The longer regimen also included a higher PPI dose. e Both studies were at high risk for bias. f One of the studies used o floxacin (not levofloxacin). 69.e3
Fallone et al Gastroenterology Vol.
151, No.
1 Supplementary Table 2.Evidence for Statement 2 (In patients with H pylori infection, we recommend that the choice of first-line therapy consider regional antibiotic resistance patterns and eradication rates) Quality assessment Summary of findings
Comments Studies
Risk of bias Inconsistency Indirectness Imprecision Other considerations a Quality
of evidence Overall
quality of evidence Eradication rates (ITT) Relative
effect (95% CI)
Regional antibiotic resistance patterns
considered Regional
antibiotic resistance patterns not considered Eradication of H pylori infection (importance of outcome: critical for decision making) Culture-guided vs empirical triple therapy 4422 Low
Culture-guided triple therapy resulted in a signi ficantly lower risk of treatment failure compared with empirical standard triple therapy 1 systematic review 47 (5 RCTs) Serious b None Serious c None None 4422
Low NA NA NA Time trends for H pylori antibiotic resistance and ef ficacy of eradication regimens Multiple
reviews of observational studies 19,22
None None
Serious None
None 4222
Very low NA NA NA a Including publication bias. b Mainly due to inadequate sequence generation and unclear/inadequate allocation concealment. c The research question is only indirectly related to this statement. July 2016
Toronto Consensus for H
Treatment 69.e4
Supplementary Table 3. Evidence for Statement 3 (In patients with H pylori infection, we recommend traditional bismuth quadruple therapy [PBMT] for 14 days as one of the options for first-line therapy) Quality assessment Summary of findings
Comments Studies
Risk of bias Inconsistency Indirectness Imprecision Other considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) (%) Relative
effect (95% CI)
PBMT Comparator Eradication of H pylori infection (importance of outcome: critical for decision making) Ef ficacy: relative to PPI-based triple regimens 4442 Moderate
Trend toward higher eradication ( w9%) found in the SR was signi ficant
only in the per- protocol analysis (not ITT) 1 SR
22 (12 RCTs) Serious b
Serious c None None 4422
Low 81.9
72.9 (PPI-based triple regimens) Nonsigni ficant
difference 1 RCT
61 None
None None
Serious None
4442 Moderate
70.0 (PBMT for 14
days) 57.5 (PAC for 14 days) Nonsigni
ficant difference Ef ficacy: absolute rates Adequately high eradication rate SR of observational studies and observational-type data from RCTs 22 None
None None
None None
4422 Low
77.6 NA NA Ef ficacy: metronidazole-resistant strains Metronidazole resistance had less impact on the success of PBMT regimens compared with clarithromycin resistance on PAC regimens 1 SR
21 (2 RCTs)
None None
Serious Serious
None 4422
Low NA NA NA Duration: PBMT for 14 days vs PBMT for 7 days 4222 Very low
Trends toward superiority of prolonged duration vs 7 days (not signi ficant)
1 SR 28 (3 RCTs) Serious None
None Very serious None 4222
Very low 77.9
69.1 Nonsigni
ficant difference Duration: PBMT for 14 days vs PBMT for 10 days 1 SR
28 (1 RCT)
Serious None
None Very serious None 4222
Very low 91.6
92.6 Nonsigni
ficant difference 1 SR d
data from 51 studies)
None Serious
Serious e Serious None 4222
Very low 78.7
75.6 Nonsigni
ficant difference Duration: PBMT for 10 days vs PBMT for 7 days 1 SR
28 (2 RCTs)
Serious None
None Very serious None 4222
Very low 87.4
81.9 Nonsigni
ficant difference a Including publication bias. b Mainly due to lack of blinding. c The studies have tested regimens of various durations (7, 10, 14 days). No subgroup analyses for 14-day regimens were performed. d Unpublished data; SR conducted for the meeting. e The comparisons were between studies, not within study. 69.e5 Fallone
et al Gastroenterology Vol. 151,
No. 1
Supplementary Table 4.Evidence for Statement 4 (In patients with H pylori infection, we recommend concomitant nonbismuth quadruple therapy [PAMC] for 14 days as one of the options for first-line therapy) Quality assessment Summary of findings
Comments Studies
Risk of bias Inconsistency Indirectness Imprecision Other considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) (%) Relative
effect (95% CI)
PAMC Comparator Eradication of H pylori infection (importance of outcome: critical for decision making) Ef ficacy: relative to PPI triple regimens 4442 Moderate
PAMC was superior to PPI triple therapy 1 SR
44 (6 RCTs)
Serious b None None None
None 4442
Moderate 91.1
80.6 Odds ratio, 2.4 (1.63 –3.55)
Ef ficacy: relative to sequential regimen PAMC was superior to sequential therapy 1 SR
69 (19 RCTs) Serious b
None None
None 4442
Moderate Not
reported Not
reported RD, 0.11
(0.07 –0.16)
Ef ficacy: relative to hybrid regimen c 2 RCTs
139,140 Serious
b None
None None
None 4442
Moderate 91.7
(for 14-day treatment) 90.0 (for 14-day treatment) Nonsigni
ficant difference Ef ficacy: absolute rates Adequately high eradication rate 1 SR 44
data from 15 studies) None None
None None
None 4422
Low 90 NA NA Duration: longer-duration PAMC or shorter-duration PAMC 4222 Very low
Trend favoring longer duration in SR (not signi
ficant) 1 SR
44 (cohort-type data from 15 studies) None None
None Serious
None 4222
Very low 92 (10 days) 89 (5 days) Not
statistically signi
ficant 1 cohort study 45 None
None Serious
d Serious
None 4222
Very low 93.3
(14 days) 86.6 (10 days) P < .01 Relative effect not reported a Including publication bias. b Mainly due to lack of blinding. c Hybrid regimen was omeprazole 40 mg and amoxicillin 1 g twice daily for 14 days plus clarithromycin 500 mg and nitroimidazole 500 mg twice daily for the final 7 days. d The longer regimen also included a higher PPI dose. July 2016
Toronto Consensus for H
Treatment 69.e6
Supplementary Table 5.Evidence for Statement 5 (In patients with H pylori infection, we recommend restricting the use of PPI triple therapy [PAC or PMC for 14 days] to areas with known low clarithromycin resistance [ <15%] or proven high local eradication rates [>85%]) Quality assessment Summary of findings
Comments Studies
Risk of bias Inconsistency Indirectness Imprecision Other considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) (%) Relative
effect (95% CI)
PPI triple therapy
Comparator Eradication of H pylori infection (Importance of outcome: critical for decision making) Ef ficacy: relative to bismuth quadruple regimen (PBMT) 4442 Moderate
Low success rates 1 SR
22 (12 RCTs) Serious b
Serious c None None 4422
Low 72.9
81.9 Nonsigni
ficant difference 1 RCT 61
None None
Serious None
4442 Moderate
57.5 (PAC for
14 days) 70.0
(PBMT for 14 days)
Nonsigni ficant
difference Low success rates Ef ficacy: relative to sequential regimen 1 SR 70 (7 RCTs) Serious d Serious e None
None None
4442 Moderate
81.3 80.8
Nonsigni ficant
difference Ef ficacy: relative to concomitant regimen PPI triple therapy was inferior to concomitant therapy
1 SR 44 (6 RCTs) Serious b None None None
None 4442
Moderate 80.6
91.1 Odds ratio, 2.4 (1.63 –3.55)
Ef ficacy: absolute rates Low success rates 1 SR
22 (observational-type data from 5 RCTs published from 2006 to 2011) None
None None
None None
4422 Low
61.5 NA Duration: 14 days vs 7 days 4442 Moderate
The quality of evidence is moderate for PAC but low for PMC 1 SR
28 (45 RCTs) Serious f
None None
None 4442
Moderate 81.9
72.9 NNT: 11 (9 –14) Duration: 14 days vs 10 days 1 SR 28 (12 RCTs) Serious b None None None
None 4442
Moderate 84.4
78.5 NNT: 17
(11 –46)
Culture-guided vs empirical triple therapy 4422
Low Indirect evidence 1 SR 47
Serious g None Serious h None None 4422
Low NA NA NA Time trends for H pylori resistance to clarithromycin and ef ficacy of eradication regimens Multiple reviews of observational studies
19,22 None
None Serious
None None
4222 Very low
NA NA NA a Including publication bias. b Mainly due to lack of blinding. c The studies have tested regimens of various durations (7, 10, 14 days). No subgroup analyses for 14-day regimens were performed. d None of the studies were at low risk for bias. e Unexplained heterogeneity. f Most of the included RCTs were at high risk or unclear risk of bias. g Mainly due to inadequate sequence generation and unclear/inadequate allocation concealment. h The research question is only indirectly related to this statement. 69.e7 Fallone
et al Gastroenterology Vol. 151,
No. 1
Supplementary Table 6.Evidence for Statement 6 (In patients with H pylori infection, we recommend against the use of levo floxacin triple therapy [PAL] as a first-line therapy) Quality assessment Summary of findings Comments
Studies Risk
of bias Inconsistency Indirectness Imprecision Other
considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) (%) Relative
effect (95% CI)
PAL Comparator Eradication of H pylori infection (IMPORTANCE OF OUTCOME: CRITICAL for decision making) Ef ficacy: relative to PAC 4222 Very low
3 RCTs 78,79,81
Serious b Serious c None
Serious None
4222 Very low
85, 80, and 81, respectively 79, 64, and 87, respectively Overall, nonsigni
ficant difference Ef ficacy: levofloxacin-resistant strains Signi ficantly lower eradication rates with PAL in levo floxacin-
resistant vs levo
floxacin- sensitive strains 2 studies (cohort-type data from 2 RCTs)
52,81 None
None Serious
None None
4222 Very low
NA NA NA a Including publication bias. b Mainly due to lack of blinding. c Two of the RCTs showed better ef ficacy for PAL, but the third showed better efficacy for PAC. Supplementary Table 7.Evidence for Statement 7 (In patients with H pylori infection, we recommend against the use of sequential nonbismuth quadruple therapy [PA followed by PMC] as a first-line therapy) Quality assessment Summary of findings Comments
Studies Risk
of bias Inconsistency Indirectness Imprecision Other
considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) (%) Relative
effect (95% CI)
Sequential therapy
Comparator Eradication of H pylori infection (importance of outcome: critical for decision making) Ef ficacy: relative to 14-day PPI triple regimens 4442 Moderate
1 SR 70 (7 RCTs) Serious b None None None
None 4442
Moderate 81.3
80.8 Nonsigni
ficant difference Ef ficacy: relative to concomitant nonbismuth quadruple therapy (PAMC) Concomitant therapy superior to sequential therapy 1 SR
69 (14 RCTs) Serious c None
None None
None 4442
Moderate 79.7
85.7 RD, 0.06
(0.03 –0.09)
Ef ficacy: relative to traditional bismuth quadruple therapy (PBMT) 1 SR 70
Serious b None None None
None 4442
Moderate 84.9
86.2 Nonsigni
ficant difference a Including publication bias. b None of the studies was at low risk of bias. c Mainly due to lack of blinding. July 2016
Toronto Consensus for H
Treatment 69.e8
Supplementary Table 8.Evidence for Statement 8 (In patients who have previously failed to respond to H pylori eradication therapy, we recommend traditional bismuth quadruple therapy [PBMT] for 14 days as an option for subsequent therapy) Quality assessment Summary of findings Comments
Studies Risk
of bias Inconsistency Indirectness Imprecision Other
considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) (%) Relative
effect (95% CI)
PBMT Comparator Eradication of H pylori infection (importance of outcome: critical for decision making) Ef ficacy: absolute rates 4422 Low
Adequately high eradication rate after failure of PPI triple therapy 1 SR (38 studies: observational studies and observational-type data from RCTs) 99 None None None
None None
4422 Low
78 NA NA Duration: PBMT for 14 days vs PBMT for 10 days Trend favoring 14 days (not signi
ficant) 1 SR (14 studies: observational studies and observational-type data from RCTs) 99 None
None Serious
b Serious
None 4222
Very low 82 77 Nonsigni ficant
difference 1 SR
c (cohort-type data from 51 studies)
None Serious
Serious b Serious None 4222
Very low 78.7
75.6 Nonsigni
ficant difference a Including publication bias. b The comparisons were between studies, not within study. c Unpublished data; SR conducted for the meeting. 69.e9 Fallone
et al Gastroenterology Vol. 151,
No. 1
Supplementary Table 9.Evidence for Statement 9 (In patients who have previously failed to respond to H pylori eradication therapy, we suggest levo floxacin-containing therapy for 14 days as an option for subsequent therapy) Quality assessment Summary of findings
Comments Studies
Risk of bias
Inconsistency Indirectness Imprecision Other
considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) (%) Relative
effect (95% CI)
PAL Comparator Eradication of H pylori infection (importance of outcome: critical for decision making) Ef ficacy: relative to bismuth quadruple regimen (PBMT) after failure of PPI triple therapy 4422 Low
Adequately high eradication rates for salvage
treatment 1 SR
99 (6 RCTs)
Serious b None None Serious
None 4422
Low 79 c 69 Nonsigni
ficant difference Ef ficacy: absolute rates with 10-day PAL after failure of concomitant nonbismuth quadruple therapy 1 SR 105
(observational type data from 3 studies) Not known d Serious
e None
Serious None
4422 Low
78 NA Ef ficacy: absolute rates after failure of sequential nonbismuth quadruple therapy 1 SR
99 (observational type data from 5 studies) None None
None None
None 4422
Low 81 NA NA Duration: 10 days vs 7 days 4222 Very low
Superiority of longer duration 1 SR
106 (observational type data from 11 studies) Not known d None None Serious
f None
4222 Very low
88.7 70.6
P < .05 Relative
effect not reported
a Including publication bias. b Mainly due to lack of blinding. c Calculated from unweighted means, but given that the weights of the included studies were very similar, it is likely that weighted estimates would produce similar results. d The SR did not report assessments of risk of bias. e Unexplained heterogeneity. f The comparisons were between studies, not within study. July 2016
Toronto Consensus for H
Treatment 69.e10
Supplementary Table 10.Evidence for Statement 10 (In patients who have previously failed to respond to a clarithromycin-containing H pylori eradication therapy, we recommend against the use of clarithromycin-containing regimens as subsequent therapy) Quality assessment Summary of findings Comments
Studies Risk
of bias Inconsistency Indirectness Imprecision Other
considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) Relative
effect (95% CI)
NA NA Eradication of H pylori infection (importance of outcome: critical for decision making) Prevalence of secondary resistance to clarithromycin 4422
Low The prevalence of secondary resistance to clarithromycin is very high (up to 70%) Multiple cohort studies and case series 20,40 None
None None
None None
4422 Low
NA NA NA Impact of clarithromycin resistance The ef
ficacy of clarithromycin- containing regimens is highly affected by clarithromycin resistance Multiple reviews of observational studies 19,22
None None
Serious None
None 4222
Very low NA NA NA a Including publication bias. Supplementary Table 11.Evidence for Statement 11 (In patients who have previously failed to respond to a levo floxacin-containing H pylori eradication therapy, we recommend against the use of levo floxacin-containing regimens as subsequent therapy) Quality assessment Summary of findings Comments
Studies Risk
of bias Inconsistency Indirectness Imprecision Other
considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) Relative effect
(95% CI) NA NA Eradication of H pylori infection (importance of outcome: critical for decision making) Prevalence of secondary resistance to levo floxacin 4422
Low The prevalence of secondary resistance to levo
floxacin is very high (up to 60%) 2 cohort studies and case series 83,84 None
None None
None None
4422 Low
NA NA NA Impact of levo floxacin resistance The ef ficacy of
levo floxacin-containing regimens is highly affected by levo floxacin resistance 2 studies (cohort-type data from 2 RCTs) 52,81 None
None Serious
None None
4222 Very low
NA NA NA a Including publication bias. 69.e11 Fallone
et al Gastroenterology Vol. 151,
No. 1
Supplementary Table 12. Evidence for Statement 12 (In patients who have previously failed to respond to H pylori eradication therapy, we recommend against the use of sequential nonbismuth quadruple therapy [PA followed by PMC] as an option for subsequent therapy) Quality assessment Summary of findings Comments
Studies Risk
of bias Inconsistency Indirectness Imprecision Other
considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) (%) Relative
effect (95% CI)
Sequential therapy
Comparator Eradication of H pylori infection (importance of outcome: critical for decision making) Ef ficacy: absolute rates 4222 Very low
2 cohort studies
109,110 None
None None
Very serious b None 4222 Very low
93 and 100 NA Ef ficacy: relative to concomitant nonbismuth quadruple therapy (PAMC) as first-line treatment PAMC was superior to sequential therapy
1 SR 69 (19 RCTs) Serious c None
None Very serious d None
4222 Very low
Not reported Not reported RD, 11% (0.7%
–16%) a Including publication bias. b Forty and 2 patients, respectively. c Mainly due to lack of blinding. d These studies tested the regimens as first-line treatments. July
2016 Toronto
Consensus for
H pylori
Treatment 69.e12
Supplementary Table 13.Evidence for Statement 13 (We recommend restricting the use of rifabutin-containing regimens to cases in which at least 3 recommended options have failed) Quality assessment Summary of findings Comments
Studies Risk
of bias Inconsistency Indirectness Imprecision Other
considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) (%) Relative
effect (95% CI)
Rifabutin- containing regimens Comparator Eradication of H pylori infection (importance of outcome: critical for decision making) Ef ficacy: absolute rates (overall) 4222 Very low
Reasonable eradication rate for those who previously failed to respond to therapy
1 SR 111
(21 studies: cohort studies and observational-type data from RCTs) None None
Serious b None None 4222
Very low 73 NA NA Ef ficacy: absolute rates (4th- or 5th-line treatment) 4222 Very low
Eradication demonstrated when used as fourth- or fifh- line therapy 1 SR 111
(7 studies: cohort studies and observational-type data from RCTs) None None
None None
Serious 4222
Very low 70 NA NA Duration: 10 –12 days vs 7 days (2nd-line treatment) 4222
Very low Evidence suggests more than 7 days is preferred 1 SR 111
(8 studies: cohort studies and observational-type data from RCTs) None None
Very serious c None Serious 4222
Very low 92 69 Not reported
a Including publication bias. b Included studies that tested the regimen as first-, second-, third, fourth-, or fifth-line treatment. c Only second-line treatment; between-studies comparisons. 69.e13 Fallone
et al Gastroenterology Vol. 151,
No. 1
Supplementary Table 14. Evidence for Statements 14 and 15 (In patients with H pylori infection, we recommend against routinely adding probiotics to eradication therapy for the purpose of reducing adverse events or increasing eradication rates) Quality assessment Summary of findings Comments
Studies Risk
of bias Inconsistency Indirectness Imprecision Other considerations a Quality of evidence Overall
quality of evidence
Eradication rates (ITT) Relative
effect (95% CI)
Probiotic supplementation Comparator Eradication of H pylori infection (importance of outcome: critical for decision making) Effect on adverse effects 4222 Very low
Very low-quality evidence
1 SR 126
(10 RCTs) Serious
b Serious
c Serious
d None
None 4222
Very low Not reported Not reported Odds ratio, 2.1 (1.4 –3.1)
Effect on eradication rates 4222
Very low Very low-quality evidence 1 SR
126 (10 RCTs) Serious b
c Serious
d None
None 4222
Very low Not reported Not reported Odds ratio, 0.3 (0.1 –0.8)
a Including publication bias. b Mainly due to lack of blinding. c Unexplained heterogeneity. d Most of the studies assessed the impact of probiotic supplementation when added to triple rather than quadruple therapy. July 2016
Toronto Consensus for H
Treatment 69.e14 Document Outline
Yüklə 0,75 Mb. Dostları ilə paylaş:
|