PPI Triple Therapy Almost as Effective as Quadruple Therapy Against H. pylori

Laurie Barclay, MD

December 20, 2002

Dec. 20, 2002 — Quadruple therapy is still the most effective for Helicobacter pylori, but triple therapy with a proton-pump inhibitor (PPI), amoxicillin, and clarithromycin is about as effective, according to the results of a randomized trial published in the December issue of Gastroenterology. However, bismuth-based triple therapy for longer than 14 days should no longer be considered.

"One-week PPI triple therapy is well tolerated and effective," write Peter H. Katelaris, from the University of Sydney in Australia, and colleagues. "The addition of PPI to bismuth triple therapy allows reduction of treatment duration with improved efficacy and tolerability, despite a high rate of metronidazole resistance."

In the QUADRATE study, infected dyspeptic patients received seven days of treatment twice daily with pantoprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg (PAC7); or seven days of treatment with pantoprazole 40 mg twice daily, bismuth subcitrate 108 mg, and tetracycline 500 mg, both four times daily, and metronidazole 200 mg three times daily and 400 mg at night (PBTM7); or 14 days of treatment with bismuth subcitrate 108 mg and tetracycline 500 mg, both four times daily, and metronidazole 200 mg three times daily and 400 mg at night (BTM14).

The investigators assessed eradication rates with the 13C-urea breath test and calculated rates both for the intention-to-treat population of 405 patients and for the population of 320 patients who actually followed protocol. Eradication rates were similar for PAC7 (78% and 82%) and PBTM7 (82% and 88%), but PBTM7 was significantly better than BTM14 (69% and 74%; P < .01).

Before treatment, resistance to metronidazole was 53% and to clarithromycin was 8%. Eradication rates for primary metronidazole-sensitive or resistant isolates in the intention-to-treat and protocol populations were 74% and 87% for PAC7 and 80% and 81% for PBTM7, compared with 76% and 55% ( P < .02) for BTM14.

For PAC7 or PBTM7 compared with BTM14, noncompliance was significantly lower (3%, 6%, and 15%, respectively; P < .001). Moderate and severe adverse events were less frequent (23%, 25%, and 45%, respectively; P < .001), and there were fewer discontinuations (2%, 3%, and 9%, respectively).

"Quadruple therapy appears to overcome pretreatment metronidazole resistance in most cases," the authors write. "Two-week bismuth triple therapy is significantly inferior to quadruple therapy and less well tolerated than both one-week therapies."

Pharmacia Australia Proprietary Limited supported this study.

Gastroenterology. 2002;123:1763-1769

Reviewed by Gary D. Vogin, MD