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Sequential eradication of Helicobacter pylori as a treatment for immune thrombocytopenia in patients with moderate thrombocytopenia: a multicenter prospective randomized phase 3 study

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Abstract

Due to several issues, standard treatments are not recommended for asymptomatic patients with moderate immune thrombocytopenia (ITP). Since platelet responses are reported in some patients with Helicobacter pylori (H. pylori)-positive ITP after eradication, we conducted a multicenter, phase 3 study to evaluate the safety and efficacy of recently established sequential eradication for these patients having moderate thrombocytopenia. Persistent or chronic ITP patients with platelet count (30 × 103 ~ 80 × 103/μL) and confirmed active H. pylori infection were randomly assigned to a treatment and a control group. The former received 10-day sequential treatment. Eradication was assessed by urea breath test at 3 months after treatment. Primary endpoint was the overall platelet response rate at 3 months in successfully eradicated treatment group and control group. Secondary endpoints were platelet response time, H. pylori eradication success rate, etc. The patient enrollment terminated early because of the change of national insurance and treatment guideline for H. pylori-positive patients in Korea during the study. Of the 28 H. pylori-positive ITP patients, 17 were randomized to the treatment group, and eradication was achieved for 15 (88.2%) at 3 months, and seven in control group after withdrawal. Statistically, significant difference in platelet response rates between the two groups were observed (p = 0.017). Our study verifies that H. pylori eradication was an effective ITP treatment for patients with H. pylori-associated moderate ITP. This sequential eradication regimen showed not only a high H. pylori eradication rate, but also a remarkable platelet response for ITP patients. Trial registration number and date of registration for these prospectively registered trials is ClinicalTrials.gov number, NCT03177629 and June 6, 2017.

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Members of the research designed the trial and protocol, collected the data, met to oversee the trial, and wrote the manuscript. The authors vouch for the completeness and accuracy of the data and for the fidelity of the trial to the protocol.

References

  1. Cines DB, Blanchette VS (2002) Immune thrombocytopenic purpura. N Engl J Med 346:995–1008. https://doi.org/10.1056/NEJMra010501

    Article  PubMed  Google Scholar 

  2. Barsam SJ, Psaila B, Forestier M, Page LK, Sloane PA, Geyer JT, Villarica GO, Ruisi MM, Gernsheimer TB, Beer JH, Bussel JB (2011) Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia. Blood 117:5723–5732. https://doi.org/10.1182/blood-2010-11-321398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kühne T, Ruggeri M, George JN (2009) Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 113:2386–2393. https://doi.org/10.1182/blood-2008-07-162503

    Article  CAS  PubMed  Google Scholar 

  4. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA (2011) The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117:4190–4207. https://doi.org/10.1182/blood-2010-08-302984

    Article  CAS  PubMed  Google Scholar 

  5. Gasbarrini A, Franceschi F, Tartaglione R, Landolfi R, Pola P, Gasbarrini G (1998) Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori. Lancet 352:878. https://doi.org/10.1016/S0140-6736(05)60004-9

    Article  CAS  PubMed  Google Scholar 

  6. Stasi R, Sarpatwari A, Segal JB, Osborn J, Evangelista ML, Cooper N, Provan D, Newland A, Amadori S, Bussel JB (2009) Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review. Blood 113:1231–1240. https://doi.org/10.1182/blood-2008-07-167155

    Article  CAS  PubMed  Google Scholar 

  7. Franchini M, Cruciani M, Mengoli C, Pizzolo G, Veneri D (2007) Effect of Helicobacter pylori eradication on platelet count in idiopathic thrombocytopenic purpura: a systematic review and meta-analysis. J Antimicrob Chemother 60:237–246. https://doi.org/10.1093/jac/dkm195

    Article  CAS  PubMed  Google Scholar 

  8. Jackson S, Beck PL, Pineo GF, Poon MC (2005) Helicobacter pylori eradication: novel therapy for immune thrombocytopenic purpura? A review of the literature. Am J Hematol 78:142–150. https://doi.org/10.1002/ajh.20250

    Article  CAS  PubMed  Google Scholar 

  9. Arnold DM, Bernotas A, Nazi I, Stasi R, Kuwana M, Liu Y, Kelton JG, Crowther MA (2009) Platelet count response to H. pylori treatment in patients with immune thrombocytopenic purpura with and without H. pylori infection: a systematic review. Haematologica 94(6):850–856

    Article  PubMed  PubMed Central  Google Scholar 

  10. Suzuki T, Matsushima M, Masui A, Watanabe K, Takagi A, Ogawa Y, Shirai T, Mine T (2005) Effect of Helicobacter pylori eradication in patients with chronic idiopathic thrombocytopenic purpura-a randomized controlled trial. Am J Gastroenterol 100:1265–1270. https://doi.org/10.1111/j.1572-0241.2005.41641.x

    Article  PubMed  Google Scholar 

  11. Tsutsumi Y, Kanamori H, Yamato H, Ehira N, Kawamura T, Umehara S, Mori A, Obara S, Ogura N, Tanaka J, Asaka M, Imamura M, Masauzi N (2005) Randomized study of Helicobacter pylori eradication therapy and proton pump inhibitor monotherapy for idiopathic thrombocytopenic purpura. Ann Hematol 84:807–811. https://doi.org/10.1007/s00277-005-1071-z

    Article  CAS  PubMed  Google Scholar 

  12. Li CX, Liu DJ, Pan CQ, Sang XF, Li X (2009) Effect of Helicobacter pylori eradication on childhood acute idiopathic thrombocytopenic purpura. Nan Fang Yi Ke Da Xue Xue Bao 29:1243–1244

    Google Scholar 

  13. Treepongkaruna S, Sirachainan N, Kanjanapongkul S, Winaichatsak A, Sirithorn S, Sumritsopak R, Chuansumrit A (2009) Absence of platelet recovery following Helicobacter pylori eradication in childhood chronic idiopathic thrombocytopenic purpura: a multi-center randomized controlled trial. Pediatr Blood Cancer 53:72–77. https://doi.org/10.1002/pbc.21991

    Article  PubMed  Google Scholar 

  14. Tang Y, Wang SC, Wang LJ, Liu Y, Wang HY, Wang ZJ (2013) Clinical significance of Helicobacter pylori in children with idiopathic thrombocytopenic purpura. Zhongguo Shi Yan Xue Ye Xue Za Zhi 21:419–421. https://doi.org/10.7534/j.issn.1009-2137.2013.02.033

    Article  PubMed  Google Scholar 

  15. Brito HSH, Braga JAP, Loggetto SR, Machado RS, Granato CFH, Kawakami E (2015) Helicobacter pyloriinfection & immune thrombocytopenic purpura in children and adolescents: a randomized controlled trial. Platelets 26:336–341. https://doi.org/10.3109/09537104.2014.911836

    Article  CAS  PubMed  Google Scholar 

  16. Kim H, Lee WS, Lee KH, Bae SH, Kim MK, Joo YD, Zang DY, Jo JC, Lee SM, Lee JH, Lee JH, Kim DY, Ryoo HM, Hyun MS, Kim HJ, CoOperative Study Group A for Hematology (COSAH) (2015) Efficacy of Helicobacter pylori eradication for the 1st line treatment of immune thrombocytopenia patients with moderate thrombocytopenia. Ann Hematol 94:739–746. https://doi.org/10.1007/s00277-014-2268-9

    Article  CAS  PubMed  Google Scholar 

  17. Kim N, Kim JJ, Choe YH, Kim HS, Kim JI, Chung IS, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association of Gastroenterology (2009) Diagnosis and treatment guidelines for Helicobacter pylori infection in Korea. Korean J Gastroenterol 54:269–278. https://doi.org/10.4166/kjg.2009.54.5.269

    Article  PubMed  Google Scholar 

  18. Lee JY, Kim N, Kim MS, Choi YJ, Lee JW, Yoon H, Shin CM, Park YS, Lee DH, Jung HC (2014) Factors affecting first-line triple therapy of Helicobacter pylori including CYP2C19 genotype and antibiotic resistance. Dig Dis Sci 59:1235–1243. https://doi.org/10.1007/s10620-014-3093-7

    Article  CAS  PubMed  Google Scholar 

  19. Boyanova L, Mitov I (2010) Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents. Expert Rev Anti-Infect Ther 8:59–70. https://doi.org/10.1586/eri.09.113

    Article  CAS  PubMed  Google Scholar 

  20. Oh HS, Lee DH, Seo JY, Cho YR, Kim N, Jeoung SH, Kim JW, Hwang JH, Park YS, Lee SH, Shin CM, Cho HJ, Jung HC, Song IS (2012) Ten-day sequential therapy is more effective than proton pump inhibitor-based therapy in Korea: a prospective, randomized study. J Gastroenterol Hepatol 27:504–509. https://doi.org/10.1111/j.1440-1746.2011.06922.x

    Article  CAS  PubMed  Google Scholar 

  21. Wu DC, Hsu PI, Wu JY, Opekun AR, Kuo CH, Wu IC, Wang SSW, Chen A, Hung WC, Graham DY (2010) Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection. Clin Gastroenterol Hepatol 8:36-41.e1. https://doi.org/10.1016/j.cgh.2009.09.030

    Article  CAS  PubMed  Google Scholar 

  22. Yoon K, Kim N (2019) Eradication rates of 10-day sequential therapy for Helicobacter pylori: results of an 8-year prospective study conducted at a tertiary Korean hospital. Korean J Gastroenterol 73:99–104. https://doi.org/10.4166/kjg.2019.73.2.99

    Article  PubMed  Google Scholar 

  23. Scaccianoce G, Hassan C, Panarese A, Piglionica D, Morini S, Zullo A (2006) Helicobacter pylori eradication with either 7-day or 10-day triple therapies, and with a 10-day sequential regimen. Can J Gastroenterol 20:113–117. https://doi.org/10.1155/2006/258768

    Article  PubMed  PubMed Central  Google Scholar 

  24. Zullo A, De Francesco V, Hassan C, Morini S, Vaira D (2007) The sequential therapy regimen for Helicobacter pylori eradication: a pooled-data analysis. Gut 56:1353–1357. https://doi.org/10.1136/gut.2007.125658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yoon H, Lee DH, Kim N, Park YS, Shin CM, Kang KK, Oh DH, Jang DK, Chung JW (2013) Meta-analysis: is sequential therapy superior to standard triple therapy for Helicobacter pylori infection in Asian adults? J Gastroenterol Hepatol 28:1801–1809. https://doi.org/10.1111/jgh.12397

    Article  PubMed  Google Scholar 

  26. George JN, el-Harake MA, Raskob GE (1994) Chronic idiopathic thrombocytopenic purpura. N Engl J Med 331:1207–1211. https://doi.org/10.1056/NEJM199411033311807

    Article  CAS  PubMed  Google Scholar 

  27. Michel M, Khellaf M, Desforges L, Lee K, Schaeffer A, Godeau B, Bierling P (2002) Autoimmune thrombocytopenic purpura and Helicobacter pylori infection. Arch Intern Med 162:1033–1036. https://doi.org/10.1001/archinte.162.9.1033

    Article  PubMed  Google Scholar 

  28. Yamanishi S, Iizumi T, Watanabe E, Shimizu M, Kamiya S, Nagata K, Kumagai Y, Fukunaga Y, Takahashi H (2006) Implications for induction of autoimmunity via activation of B-1 cells by Helicobacter pylori urease. Infect Immun 74:248–256. https://doi.org/10.1128/IAI.74.1.248-256.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kuwana M, Okazaki Y, Ikeda Y (2009) Splenic macrophages maintain the anti-platelet autoimmune response via uptake of opsonized platelets in patients with immune thrombocytopenic purpura. J Thromb Haemost 7:322–329. https://doi.org/10.1111/j.1538-7836.2008.03161.x

    Article  CAS  PubMed  Google Scholar 

  30. Kuwana M (2014) Helicobacter pylori-associated immune thrombocytopenia: clinical features and pathogenic mechanisms. World J Gastroenterol 20:714–723. https://doi.org/10.3748/wjg.v20.i3.714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Jung HK, Kang SJ, Lee YC, Yang HJ, Park SY, Shin CM, Kim SE, Lim HC, Kim JH, Nam SY, Shin WG, Park JM, Choi IJ, Kim JG, Choi M, Korean College of Helicobacter and Upper Gastrointesinal Research (2021) Evidence based guidelines for the treatment of Helicobacter pylori infection in Korea 2020. Korean J Intern Med 36:807–838. https://doi.org/10.3904/kjim.2020.701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kato M, Ota H, Okuda M, Kikuchi S, Satoh K, Shimoyama T, Suzuki H, Handa O, Furuta T, Mabe K, Murakami K, Sugiyama T, Uemura N, Takahashi S (2019) Guidelines for the management of Helicobacter pylori infection in Japan: 2016, revised edition. Helicobacter 24(4):e12597. https://doi.org/10.1111/hel.12597

    Article  PubMed  Google Scholar 

  33. Lee A, Hong J, Chung H, Koh Y, Cho SJ, Byun JM, Kim SG, Kim I (2020) Helicobacter pylori eradication affects platelet count recovery in immune thrombocytopenia. Sci Rep 10:9370. https://doi.org/10.1038/s41598-020-66460-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ianaro A, Ialenti A, Maffia P, Sautebin L, Rombolà L, Carnuccio R, Iuvone T, D’Acquisto F, Di Rosa MD (2000) Anti-inflammatory activity of macrolide antibiotics. J Pharmacol Exp Ther 292:156–163

    CAS  PubMed  Google Scholar 

  35. Hwang JJ, Lee DH, Yoon H, Shin CM, Park YS, Kim N (2016) The effects of Helicobacter pylori eradication therapy for chronic idiopathic thrombocytopenic purpura. Gut Liver 10:356–361. https://doi.org/10.5009/gnl14483

    Article  CAS  PubMed  Google Scholar 

  36. Daou S, Federici L, Zimmer J, Maloisel F, Serraj K, Andrès E (2008) Idiopathic thrombocytopenic purpura in elderly patients: a study of 47 cases from a single reference center. Eur J Intern Med 19:447–451. https://doi.org/10.1016/j.ejim.2007.07.006

    Article  PubMed  Google Scholar 

  37. Ando K, Shimamoto T, Tauchi T, Ito Y, Kuriyama Y, Gotoh A, Miyazawa K, Kimura Y, Kawai T, Ohyashiki K (2003) Can eradication therapy for Helicobacter pylori really improve the thrombocytopenia in idiopathic thrombocytopenic purpura? Our experience and a literature review. Int J Hematol 77:239–244. https://doi.org/10.1007/BF02983780

    Article  PubMed  Google Scholar 

  38. Sato R, Murakami K, Watanabe K, Okimoto T, Miyajima H, Ogata M, Ohtsuka E, Kodama M, Saburi Y, Fujioka T, Nasu M (2004) Effect of Helicobacter pylori eradication on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura. Arch Intern Med 164:1904–1907. https://doi.org/10.1001/archinte.164.17.1904

    Article  PubMed  Google Scholar 

  39. Inaba T, Mizuno M, Take S, Suwaki K, Honda T, Kawai K, Fujita M, Tamura T, Yokota K, Oguma K, Okada H, Shiratori Y (2005) Eradication of Helicobacter pylori increases platelet count in patients with idiopathic thrombocytopenic purpura in Japan. Eur J Clin Invest 35:214–219. https://doi.org/10.1111/j.1365-2362.2005.01471.x

    Article  CAS  PubMed  Google Scholar 

  40. Stasi R, Rossi Z, Stipa E, Amadori S, Newland AC, Provan D (2005) Helicobacter pylori eradication in the management of patients with idiopathic thrombocytopenic purpura. Am J Med 118:414–419. https://doi.org/10.1016/j.amjmed.2004.09.014

    Article  PubMed  Google Scholar 

  41. Fujimura K, Kuwana M, Kurata Y, Imamura M, Harada H, Sakamaki H, Teramura M, Koda K, Nomura S, Sugihara S, Shimomura T, Fujimoto TT, Oyashiki K, Ikeda Y (2005) Is eradication therapy useful as the first line of treatment in Helicobacter pylori-positive idiopathic thrombocytopenic purpura? Analysis of 207 eradicated chronic ITP cases in Japan. Int J Hematol 81:162–168. https://doi.org/10.1532/ijh97.04146

    Article  PubMed  Google Scholar 

  42. Kodama M, Kitadai Y, Ito M, Kai H, Masuda H, Tanaka S, Yoshihara M, Fujimura K, Chayama K (2007) Immune response to CagA protein is associated with improved platelet count after Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura. Helicobacter 12:36–42. https://doi.org/10.1111/j.1523-5378.2007.00477.x

    Article  CAS  PubMed  Google Scholar 

  43. Satake M, Nishikawa J, Fukagawa Y, Akashi K, Okamoto T, Yoshida T, Hirano A, Maetani N, Iida Y, Sakaida I (2007) The long-term efficacy of Helicobacter pylori eradication therapy in patients with idiopathic thrombocytopenic purpura. J Gastroenterol Hepatol 22:2233–2237. https://doi.org/10.1111/j.1440-1746.2007.04845.x

    Article  CAS  PubMed  Google Scholar 

  44. Emilia G, Luppi M, Zucchini P, Morselli M, Potenza L, Forghieri F, Volzone F, Jovic G, Leonardi G, Donelli A, Torelli G (2007) Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles. Blood 110:3833–3841. https://doi.org/10.1182/blood-2006-12-063222

    Article  CAS  PubMed  Google Scholar 

  45. Jarque I, Andreu R, Llopis I, De la Rubia JD, Gomis F, Senent L, Jiménez C, Martín G, Martínez JA, Sanz GF, Ponce J, Sanz MA (2001) Absence of platelet response after eradication of Helicobacter pylori infection in patients with chronic idiopathic thrombocytopenic purpura. Br J Haematol 115:1002–1003. https://doi.org/10.1046/j.1365-2141.2001.03194.x

    Article  CAS  PubMed  Google Scholar 

  46. Michel M, Cooper N, Jean C, Frissora C, Bussel JB (2004) Does Helicobacter pylori initiate or perpetuate immune thrombocytopenic purpura? Blood 103:890–896. https://doi.org/10.1182/blood-2003-03-0900

    Article  CAS  PubMed  Google Scholar 

  47. Suvajdzić N, Stanković B, Artiko V, Cvejić T, Bulat V, Bakrac M, Colović M, Obradović V, Atkinson HDE (2006) Helicobacter pylori eradication can induce platelet recovery in chronic idiopathic thrombocytopenic purpura. Platelets 17:227–230. https://doi.org/10.1080/09537100500462487

    Article  CAS  PubMed  Google Scholar 

  48. Ahn ER, Tiede MP, Jy W, Bidot CJ, Fontana V, Ahn YS (2006) Platelet activation in Helicobacter pylori-associated idiopathic thrombocytopenic purpura: eradication reduces platelet activation but seldom improves platelet counts. Acta Haematol 116:19–24. https://doi.org/10.1159/000092343

    Article  PubMed  Google Scholar 

  49. Estrada-Gómez RA, Parra-Ortega I, Martínez-Barreda C, Ruiz-Argüelles GJ (2007) Helicobacter pylori infection and thrombocytopenia: a single-institution experience in Mexico. Rev Invest Clin 59:112–115

    PubMed  Google Scholar 

  50. O’Neill CM, Weitz IC, O’Connell C, Liebman HA (2019) Ethnic and racial difference in Helicobacter pylori infection in patients with immune thrombocytopenia treated at a major urban medical center. Platelets 30:413–417. https://doi.org/10.1080/09537104.2018.1453061

    Article  CAS  PubMed  Google Scholar 

  51. 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 (2017) Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology 153:420–429. https://doi.org/10.1053/j.gastro.2017.04.022

    Article  PubMed  Google Scholar 

  52. Linz B, Balloux F, Moodley Y, Manica A, Liu H, Roumagnac P, Falush D, Stamer C, Prugnolle F, van der Merwe SW, Yamaoka Y, Graham DY, Perez-Trallero E, Wadstrom T, Suerbaum S, Achtman M (2007) An African origin for the intimate association between humans and Helicobacter pylori. Nature 445:915–918. https://doi.org/10.1038/nature05562

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Additionally, we thank Nayoung Kim (Department of Internal Medicine, Seoul National University Bundang Hospital, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) for helping the development of the sequential treatment regimen used in this study.

Funding

This work was supported by a grant (13–2017-016) from the SNUBH Research Fund.

Author information

Author notes

  1. Boram Han and Hyo Jung Kim contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea

    Boram Han & Hyo Jung Kim

  2. Division of Hematology-Oncology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea

    Ho-Young Yhim

  3. Division of Hematology-Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea

    Doyeun Oh

  4. Division of Hematology-Oncology, Department of Internal Medicine, Daegu Catholic University Hospital, Daegu, Republic of Korea

    Sung Hwa Bae

  5. Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea

    Ho-Jin Shin

  6. Division of Hematology-Oncology, Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Republic of Korea

    Won-Sik Lee

  7. Division of Hematology-Oncology, Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea

    JiHyun Kwon

  8. Division of Hemato-Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea

    Jeong-Ok Lee & Soo-Mee Bang

  9. Department of Prevention Medicine, University of Ulsan College of Medicine, Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul, Republic of Korea

    Hwa Jung Kim

  10. Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul, Republic of Korea

    Hwa Jung Kim

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  1. Boram Han
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  11. Soo-Mee Bang
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Contributions

Hyo Jung Kim, Hwa Jung Kim, and Soo-Mee Bang designed the study concept; Boram Han, Hyo Jung Kim, Ho-Young Yhim, Doyeun Oh, Sung Hwa Bae, Ho-Jin Shin, Won-Sik Lee, JiHyun Kwon, Jeong-Ok Lee, and Soo-Mee Bang performed the study; Boram Han, Hyo Jung Kim, and Hwa Jung Kim analyzed the study; Boram Han wrote the manuscript; Hyo Jung Kim and Soo-Mee Bang critically reviewed the study; Boram Han and Hyo Jung Kim contributed equally to this work.

Corresponding author

Correspondence to Soo-Mee Bang.

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The trial was conducted in accordance with the revised Helsinki guidelines. The study protocol was approved by institutional review boards in the participating institutions.

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The authors declare no competing interests.

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Han, B., Kim, H.J., Yhim, HY. et al. Sequential eradication of Helicobacter pylori as a treatment for immune thrombocytopenia in patients with moderate thrombocytopenia: a multicenter prospective randomized phase 3 study. Ann Hematol 101, 1435–1445 (2022). https://doi.org/10.1007/s00277-022-04782-2

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