Olga P Nyssen1, Angeles Perez-Aisa2, Luis Rodrigo3, Manuel Castro4, Pilar Mata Romero5, Juan Ortuño6, Jesus Barrio7, Jose Maria Huguet8, Ines Modollel9, Noelia Alcaide10, Alfredo Lucendo11, Xavier Calvet12, Monica Perona13, Barbara Gomez14, Blas Jose Gomez Rodriguez15, Pilar Varela16, Manuel Jimenez-Moreno17, Manuel Dominguez-Cajal18, Liliana Pozzati19, Diego Burgos20, Luis Bujanda21, Jenifer Hinojosa2, Javier Molina-Infante5, Tommaso Di Maira6, Luis Ferrer8, Luis Fernández-Salazar10, Ariadna Figuerola12, Llucia Tito14, Cristobal de la Coba16, Judith Gomez-Camarero17, Nuria Fernandez2, Maria Caldas1, Ana Garre1, Elena Resina1, Ignasi Puig22, Colm O'Morain23, Francis Megraud24, Javier P Gisbert1. 1. Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. 2. Gastroenterology Unit, Agencia Sanitaria Costa del Sol, Málaga, Spain. 3. Gastroenterology Unit, Hospital Universitario Central de Asturias, Oviedo, Spain. 4. Gastroenterology Unit, Hospital de Valme and CIBEREHD, Sevilla, Spain. 5. Gastroenterology Unit, Hospital San Pedro de Alcántara and CIBEREHD, Cáceres, Spain. 6. Gastroenterology Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain. 7. Gastroenterology Unit, Hospital Rio Hortega, Valladolid, Spain. 8. Gastroenterology Unit, Consorci Hospital General Universitari Valencia, Valencia, Spain. 9. Gastroenterology Unit, Consorci Sanitari Terrassa, Terrassa, Spain. 10. Gastroenterology Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain. 11. Gastroenterology Unit, Hospital de Tomelloso, Ciudad Real, Spain. 12. Gastroenterology Unit, Hospital de Sabadell and CIBEREHD, Barcelona, Spain. 13. Gastroenterology Unit, Hospital Quiron, Marbella, Spain. 14. Gastroenterology Unit, Hospital de Mataró, Barcelona, Spain. 15. Gastroenterology Unit, Hospital Virgen de la Macarena, Sevilla, Spain. 16. Gastroenterology Unit, Hospital de Cabueñes Gijon, Spain. 17. Gastroenterology Unit, Hospital Universitario de Burgos, Spain. 18. Gastroenterology Unit, Hospital San Jorge Huesca, Spain. 19. Gastroenterology Unit, Hospital de Mérida, Mérida, Spain. 20. Gastroenterology Unit, Hospital Ramon y Cajal, Madrid, Spain. 21. Gastroenterology Unit, Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain. 22. Gastroenterology Unit, Althaia Xarxa Assistencial Universitària de Manresa and Universitat de Vic-Universitat Central de Catalunya (UVicUCC), Manresa, Spain. 23. Gastroenterology Unit, Trinity College, Dublin, Ireland. 24. Gastroenterology Unit, Centre National de Référence des Campylobacters et Hélicobacters, Université de Bordeaux, Bordeaux, France.
Abstract
BACKGROUND: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.
BACKGROUND: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.