Rescue Therapy for Helicobacter pylori Eradication: A Randomized Non-Inferiority Trial of Amoxicillin or Tetracycline in Bismuth Quadruple Therapy.
To compare the efficacy and safety of bismuth-containing quadruple therapy with tetracycline or amoxicillin for rescue treatment of Helicobacter pylori.



The study was a non-inferiority trial of H. pylori eradication with at least two previous treatment failures. Subjects were randomized to receive 14-day therapy with b.i.d. lansoprazole 30 mg and bismuth 220 mg, plus metronidazole 400 mg q.i.d and amoxicillin 1 g t.i.d (amoxicillin group) or tetracycline 500 mg q.i.d (tetracycline group). Antimicrobial susceptibility was assessed by the agar-dilution method. Primary outcome was H. pylori eradication at 6 weeks after treatment.



In all, 312 subjects were randomized, 13 were lost to follow-up; 29 violated the protocol. The intention-to-treat, per-protocol, and modified intention-to-treat eradication rates were (amoxicillin) 88.5% (138/156, 95% confidence interval (CI) 83.4-93.5%), 93.7% (133/142, 95% CI 89.7-97.7%), and 92.6% (138/149, 95% CI 88.4-96.8%). With tetracycline, they were 87.2% (136/156, 95% CI 81.9-92.4%), 95.3% (122/128, 95% CI 91.7-99.0%), and 90.7% (136/150, 95% CI 86.0-95.3%). Amoxicillin-, tetracycline-, and metronidazole-resistant rates were 8.3, 1.0, and 87.8%, respectively. Non-inferiority was confirmed (P<0.025). Metronidazole resistance did not affect the efficacy of either therapy. Compliance was greater and moderate and severe adverse events were less among those receiving amoxicillin than those receiving tetracycline.



The novel bismuth-containing quadruple therapy with metronidazole and amoxicillin is an alternative to classical bismuth quadruple therapy for H. pylori rescue treatment as it provides similar eradication with superior safety and compliance.
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Qi
Q
Chen
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Wei
W
Zhang
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Qingyan
Q
Fu
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Xiao
X
Liang
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Wenzhong
W
Liu
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Shudong
S
Xiao
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Hong
H
Lu
D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use*; D000863:Antacids / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001729:Bismuth / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004415:Dyspepsia / Q000150:complications / Q000188:drug therapy*; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D064747:Lansoprazole / Q000627:therapeutic use; D008297:Male; D055118:Medication Adherence; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D010437:Peptic Ulcer / Q000150:complications / Q000188:drug therapy*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D013752:Tetracycline / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
D000863:Antacids; D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D008795:Metronidazole; D000658:Amoxicillin; D013752:Tetracycline; D001729:Bismuth
Am Fam Physician. 2007 Feb 1;75(3):351-8
17304866
Aliment Pharmacol Ther. 2014 Jul;40(2):171-7
24863854
J Antimicrob Chemother. 1993 Jan;31(1):9-20
8444678
Gut. 2012 May;61(5):646-64
22491499
Gut. 2013 Jan;62(1):34-42
22580412
Therap Adv Gastroenterol. 2012 Mar;5(2):103-9
22423259
J Clin Pathol. 1988 Feb;41(2):207-10
3280609
Aliment Pharmacol Ther. 2007 Aug 1;26(3):343-57
17635369
Clin Gastroenterol Hepatol. 2013 Jul;11(7):802-7.e1
23376004
Gut. 2010 Aug;59(8):1143-53
20525969
Scand J Gastroenterol. 2015;50(10):1185-90
25881966
Gut. 2015 Nov;64(11):1715-20
26338726
Lancet. 2011 Mar 12;377(9769):905-13
21345487
Aliment Pharmacol Ther. 2002 Feb;16(2):315-24
11860415
Gastroenterol Clin North Am. 2015 Sep;44(3):537-63
26314667
J Gastroenterol Hepatol. 2008 Jan;23(1):42-5
17559359
J Clin Pharmacol. 2014 Mar;54(3):258-66
24122836
Gut. 2016 May;65(5):870-8
26848181
J Clin Gastroenterol. 2008 Feb;42(2):139-42
18209581
Med Sci Monit. 2007 Apr;13(4):CR187-90
17392649
Helicobacter. 1996 Mar;1(1):6-19
9398908
Aliment Pharmacol Ther. 2003 Aug 1;18(3):347-53
12895220