Efficacy of two-week therapy with doxycycline-based quadruple regimen versus levofloxacin concomitant regimen for helicobacter pylori infection: a prospective single-center randomized controlled trial

Marouf Alhalabi, Mohammed Waleed Alassi, Kamal Alaa Eddin, Khaled Cheha, Marouf Alhalabi, Mohammed Waleed Alassi, Kamal Alaa Eddin, Khaled Cheha

Abstract

Background: Antibiotic-resistance reduces the efficacy of conventional triple therapy for Helicobacter Pylori infections worldwide, which necessitates using various treatment protocols. We used two protocols, doxycycline-based quadruple regimen and concomitant levofloxacin regimen. The aim was to assess the effectiveness of doxycycline-based quadruple regimen for treating Helicobacter Pylori infections compared with levofloxacin concomitant regimen as empirical first-line therapy based on intention-to-treat (ITT) and per-protocol analyses (PPA) in Syrian population.

Settings and design: An open-label, randomised, parallel, superiority clinical trial.

Methods: We randomly assigned 78 naïve patients who tested positive for Helicobacter Pylori gastric infection, with a 1:1 ratio to (D-group) which received (bismuth subsalicylate 524 mg four times daily, doxycycline 100 mg, tinidazole 500 mg, and esomeprazole 20 mg, each twice per day for 2 weeks), or (L-group) which received (levofloxacin 500 mg daily, tinidazole 500 mg, amoxicillin 1000 mg, and esomeprazole 20 mg each twice per day for two weeks). We confirmed Helicobacter Pylori eradication by stool antigen test 8 weeks after completing the treatment.

Results: Thirty-nine patients were allocated in each group. In the D-group, 38 patients completed the follow-up, 30 patients were cured. While in the L-group, 39 completed the follow-up, 32patients were cured. According to ITT, the eradication rates were 76.92%, and 82.05%, for the D-group and L-group respectively. Odds ratio with 95% confidence interval was 1.371 [0.454-4.146]. According to PPA, the eradication rates were 78.9%, and 82.05% for the D-group and L-group respectively. The odds ratio with 95% confidence interval was 1.219 [0.394-3.774]. We didn't report serious adverse effects.

Conclusions: Levofloxacin concomitant therapy wasn't superior to doxycycline based quadruple therapy. Further researches are required to identify the optimal first-line treatment for Helicobacter-Pylori Infection in the Syrian population.

Trial registration: We registered this study as a standard randomized clinical trial ( Clinicaltrial.gov , identifier- NCT04348786 , date:29-January-2020).

Keywords: Bismuth; Doxycycline; Helicobacter pylori; Levofloxacin; Quadruple regimen; Syria; Tinidazole.

Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow of the study

References

    1. Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, Malfertheiner P, Graham DY, Wong VWS, Wu JCY, Chan FKL, Sung JJY, Kaplan GG, Ng SC. Global prevalence of helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017;153(2):420–429. doi: 10.1053/j.gastro.2017.04.022.
    1. Peterson WL. Helicobacter pylori and peptic ulcer disease. N Engl J Med. 1991;324(15):1043–1048. doi: 10.1056/NEJM199104113241507.
    1. Caselli M, Alvisi V. Helicobacter pylori and peptic-ulcer disease. Lancet. 2002;359(9321):1943–1944. doi: 10.1016/S0140-6736(02)08746-9.
    1. Henriksson AE, Edman AC, Held M, Wadström T. Helicobacter pylori and acute bleeding peptic ulcer. Eur J Gastroenterol Hepatol. 1995;7(8):769–771.
    1. Ishaq S, Nunn L. Helicobacter pylori and gastric cancer: a state of the art review. Gastroenterol Hepatol Bed Bench. 2015;8(Suppl 1):S6–14.
    1. Wotherspoon AC. Gastric MALT lymphoma and helicobacter pylori. Yale J Biol Med. 1996;69(1):61–68.
    1. Kim BJ, Kim HS, Jang HJ, Kim JH. Helicobacter pylori eradication in idiopathic thrombocytopenic Purpura: a meta-analysis of randomized trials. Gastroenterol Res Pract. 2018;2018:1–8. doi: 10.1155/2018/6090878.
    1. Monzón H, Forné M, Esteve M, Rosinach M, Loras C, Espinós JC, Viver JM, Salas A, Fernández-Bañares F. Helicobacter pylori infection as a cause of iron deficiency anaemia of unknown origin. World J Gastroenterol. 2013;19(26):4166–4171. doi: 10.3748/wjg.v19.i26.4166.
    1. Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7–14 June 1994. IARC Monogr Eval Carcinog Risks Hum. 1994;61:1–241.
    1. Helicobacter pylori Eradication to Prevent Gastric Cancer in a High-Risk Region of China: A Randomized Controlled Trial | Gastroenterology | JAMA | JAMA Network. . Accessed 4 Jul 2020.
    1. Ghotaslou R, Leylabadlo HE, Asl YM. Prevalence of antibiotic resistance in helicobacter pylori: a recent literature review. World J Methodol. 2015;5(3):164–174. doi: 10.5662/wjm.v5.i3.164.
    1. Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Gastroenterology. 2018;155:1372–1382. doi: 10.1053/j.gastro.2018.07.007.
    1. Malfertheiner P, Megraud F, O’Morain CA, Gisbert JP, Kuipers EJ, Axon AT, et al. Management of Helicobacter pylori infection—the Maastricht V/Florence consensus report. Gut. 2017;66(1):6–30. doi: 10.1136/gutjnl-2016-312288.
    1. Cheha KM, Dib SOA, Alhalabi MM. Pilot study: comparing efficacy of 14-day triple therapy clarithromycin versus levofloxacin on eradication of helicobacter pylori infection in Syrian population single-center experience. Avicenna J Med. 2018;8(1):14–17. doi: 10.4103/ajm.AJM_70_17.
    1. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of helicobacter pylori infection. Am J Gastroenterol. 2017;112(2):212–239. doi: 10.1038/ajg.2016.563.
    1. Niv Y. Doxycycline in eradication therapy of helicobacter pylori--a systematic review and meta-analysis. Digestion. 2016;93(2):167–173. doi: 10.1159/000443683.
    1. Berrutti M, Pellicano R, Astegiano M, Smedile A, Saracco G, Morgando A, de Angelis C, Repici A, Fagoonee S, Leone N, Rizzetto M. Helicobacter pylori eradication: metronidazole or tinidazole? Data from Turin, Italy. Minerva Gastroenterol Dietol. 2008;54(4):355–358.
    1. Moshkowitz M, Konikoff FM, Peled Y, Brill S, Hallak A, Tiomny E, et al. One week triple therapy with omeprazole, clarithromycin and tinidazole for helicobacter pylori: differing efficacy in previously treated and untreated patients. Aliment Pharmacol Ther. 1996;10(6):1015–1019. doi: 10.1046/j.1365-2036.1996.96268000.x.
    1. Hart CA, Kariuki S. Antimicrobial resistance in developing countries. BMJ. 1998;317(7159):647–650. doi: 10.1136/bmj.317.7159.647.
    1. Satoh K, Kimura K, Taniguchi Y, Kihira K, Takimoto T, Saifuku K, Kawata H, Tokumaru K, Kojima T, Seki M, Ido K, Fujioka T. Biopsy sites suitable for the diagnosis of helicobacter pylori infection and the assessment of the extent of atrophic gastritis. Am J Gastroenterol. 1998;93(4):569–573. doi: 10.1111/j.1572-0241.1998.166_b.x.
    1. Lee JY, Kim N. Diagnosis of helicobacter pylori by invasive test: histology. Ann Transl Med. 2015;3. 10.3978/j.issn.2305-5839.2014.11.03.
    1. Veijola L, Myllyluoma E, Korpela R, Rautelin H. Stool antigen tests in the diagnosis of helicobacter pylori infection before and after eradication therapy. World J Gastroenterol. 2005;11(46):7340–7344. doi: 10.3748/wjg.v11.i46.7340.
    1. Basu PP, Rayapudi K, Pacana T, Shah NJ, Krishnaswamy N, Flynn M. A randomized study comparing levofloxacin, omeprazole, Nitazoxanide, and doxycycline versus triple therapy for the eradication of helicobacter pylori. Am J Gastroenterol. 2011;106(11):1970–1975. doi: 10.1038/ajg.2011.306.
    1. Borody TJ, George LL, Brandl S, Andrews P, Lenne J, Moore-Jones D, Devine M, Walton M. Helicobacter pylori eradication with doxycycline-metronidazole-bismuth subcitrate triple therapy. Scand J Gastroenterol. 1992;27(4):281–284. doi: 10.3109/00365529209000075.
    1. Wang Z, Wu S. Doxycycline-based quadruple regimen versus routine quadruple regimen for rescue eradication of helicobacter pylori: an open-label control study in Chinese patients. Singap Med J. 2012;53(4):273–276.
    1. Federico A, Nardone G, Gravina AG, Iovene MR, Miranda A, Compare D, et al. Efficacy of 5-day levofloxacin-containing concomitant therapy in eradication of Helicobacter pylori infection. Gastroenterology. 2012;143:55–61. doi: 10.1053/j.gastro.2012.03.043.
    1. Zhong B. How to calculate sample size in randomized controlled trial? J Thorac Dis. 2009;1(1):51–54.
    1. Gupta K, Attri J, Singh A, Kaur H, Kaur G. Basic concepts for sample size calculation: critical step for any clinical trials! Saudi J Anaesth. 2016;10(3):328–331. doi: 10.4103/1658-354X.174918.
    1. Sakpal TV. Sample size estimation in clinical trial. Perspect Clin Res. 2010;1:67.
    1. Eshraghian A. Epidemiology of helicobacter pylori infection among the healthy population in Iran and countries of the eastern Mediterranean region: a systematic review of prevalence and risk factors. World J Gastroenterol. 2014;20(46):17618–17625. doi: 10.3748/wjg.v20.i46.17618.
    1. Kuo Y-T, Liou J-M, El-Omar EM, Wu J-Y, Leow AHR, Goh KL, et al. Primary antibiotic resistance in helicobacter pylori in the Asia-Pacific region: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017;2(10):707–715. doi: 10.1016/S2468-1253(17)30219-4.
    1. Graham DY, Lu H, Yamaoka Y. A report card to grade helicobacter pylori therapy. Helicobacter. 2007;12(4):275–278. doi: 10.1111/j.1523-5378.2007.00518.x.
    1. Essa AS, Kramer JR, Graham DY, Treiber G. Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing “concomitant therapy” versus triple therapy for Helicobacter pylori eradication. Centre for Reviews and Dissemination (UK); 2009. . Accessed 4 Sep 2020.
    1. Yuan Y, Ford AC, Khan KJ, Gisbert JP, Forman D, Leontiadis GI, Tse F, Calvet X, Fallone C, Fischbach L, Oderda G, Bazzoli F, Moayyedi P. Optimum duration of regimens for Helicobacter pylori eradication. Cochrane Database Syst Rev. 2013;(12):CD008337. 10.1002/14651858.CD008337.pub2.
    1. Haddadi M-H, Negahdari B, Asadolahi R, Bazargani A. Helicobacter pylori antibiotic resistance and correlation with cagA motifs and homB gene. Postgrad Med. 2020;:1–4l.
    1. Levy SB, Star L, Kupferberg ED. The misuse of antibiotice. Medical Ethics (Burlington, Mass) 2004;11:5–8.
    1. Schroeck JL, Ruh CA, Sellick JA, Ott MC, Mattappallil A, Mergenhagen KA. Factors associated with antibiotic misuse in outpatient treatment for upper respiratory tract infections. Antimicrob Agents Chemother. 2015;59(7):3848–3852. doi: 10.1128/AAC.00652-15.
    1. Giono-Cerezo S, Santos-Preciado JI, Morfin-Otero MDR, Torres-Lopez FJ, Alcantar-Curiel MD. Antimicrobial resistance. Its importance and efforts to control it. Gac Med Mex. 2020;156(2):171–178. doi: 10.24875/GMM.M20000358.
    1. Chokshi A, Sifri Z, Cennimo D, Horng H. Global contributors to antibiotic resistance. J Global Infect Dis. 2019;11(1):36–42. doi: 10.4103/jgid.jgid_110_18.
    1. Kardas P. Patient compliance with antibiotic treatment for respiratory tract infections. J Antimicrob Chemother. 2002;49(6):897–903. doi: 10.1093/jac/dkf046.
    1. Grob PR. Antibiotic prescribing practices and patient compliance in the community. Scand J Infect Dis Suppl. 1992;83:7–14.
    1. Eells SJ, Nguyen M, Jung J, Macias-Gil R, May L, Miller LG. Relationship between adherence to Oral antibiotics and Postdischarge clinical outcomes among patients hospitalized with Staphylococcus aureus skin infections. Antimicrob Agents Chemother. 2016;60(5):2941–2948. doi: 10.1128/AAC.02626-15.

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