A randomized comparison of quadruple and triple therapies for Helicobacter pylori eradication: The QUADRATE Study.
OBJECTIVE
Direct comparisons of bismuth and proton pump inhibitor (PPI)-based triple and quadruple therapies for Helicobacter pylori eradication are lacking. To address this, a randomized study was conducted.


METHODS
Infected dyspeptic patients received pantoprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all twice daily, for 7 days (PAC7); or pantoprazole 40 mg twice daily, bismuth subcitrate 108 mg, and tetracycline 500 mg, both 4 times daily, and metronidazole 200 mg 3 times daily and 400 mg at night for 7 days (PBTM7); bismuth subcitrate 108 mg and tetracycline 500 mg, both 4 times daily, and metronidazole 200 mg 3 times daily and 400 mg at night for 14 days (BTM14). Outcome was assessed with (13)C-urea breath test.


RESULTS
Eradication rates (intention to treat [n = 405]/per protocol [n = 320]) were similar for PAC7 (78%/82%) and PBTM7 (82%/88%); the latter significantly superior to BTM14 (69%/74%; P < 0.01). Pretreatment metronidazole resistance (MR) was 53% and clarithromycin resistance was 8%. Eradication rates for primary metronidazole sensitive/resistant isolates were 74%/87% with PAC7 and 80%/81% for PBTM7, compared with 76%/55% (P < 0.02) for BTM14. Noncompliance was greater with BTM14 (15%; P < 0.001) than PAC7 (3%) or PBTM7 (6%). Moderate-severe adverse events were more common with BTM14 (45%; P < 0.001), than PAC7 (23%) or PBTM7 (25%) with more discontinuations (9%, 2%, 3%, respectively).


CONCLUSIONS
One-week PPI triple therapy is well tolerated and effective. The addition of PPI to bismuth triple therapy allows reduction of treatment duration with improved efficacy and tolerability, despite a high rate of MR. Quadruple therapy appears to overcome pretreatment MR in most cases. Two-week bismuth triple therapy is significantly inferior to quadruple therapy and less well tolerated than both 1-week therapies.
Katelaris
Peter H
PH
Department of Gastroenterology, Concord Hospital, University of Sydney, West, Australia. pkatelar@mail.usyd.edu.au
Forbes
Geoffrey M
GM
Talley
Nicholas J
NJ
Crotty
Brendan
B
D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D016481:Helicobacter Infections / Q000175:diagnosis / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000627:therapeutic use; D010349:Patient Compliance; D054328:Proton Pump Inhibitors; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; D054328:Proton Pump Inhibitors; C002791:bismuth tripotassium dicitrate