Major North American Study of Eradication Treatment of Helicobacter pylori in Duodenal Ulcer Patients ...

Bismuth-Based Quadruple Therapy Using a Single Capsule of Bismuth Biskalcitrate, Metronidazole, and Tetracycline Given with Omeprazole Versus Omeprazole, Amoxicillin, and Clarithromycin for Eradication of Helicobacter pylori in Duodenal Ulcer Patients.

A Prospective, Randomized, Multicenter, North American Trial

Loren Laine, Richard Hunt, Hala El-Zimaity, Bich Nguyen, Michael Osato, Jean Spénard

Am J Gastroenterol 2003; 98:562-567.

Data based on a North American, multicenter, randomized, active controlled trial to assess the efficacy of bismuth-based quadruple therapy with (OBMT) using a 3-in-1 capsule of BMT; bismuth subcitrate (140 mg), metronidazole (125 mg) and tetracycline (125 mg) QID given with omeprazole BID (20 mg) for 10 days compared with triple therapy (OAC) with omeprazole (20mg), amoxicillin (500mg), and clarithromycin (500mg) BID in treatment of patients with Helicobacter pylori infection and duodenal ulcers. 138 patients received OBMT and 137 OAC. Overall eradication rates were 87.7% for OBMT and 83.2% for OAC. OAC eradicated 92.1% clarithromycin sensitive strains and 21.4% clarithromycin resistant strains (p<0.001).

Overcoming Antimicrobial Resistance

"However, OBMT [omeprazole, bismuth biskalcitrate, metronidazole, and tetracycline] provided markedly better rates of eradication in strains with clarithromycin resistance because the eradication rate with OAC [omeprazole, amoxicillin and clarithromycin] was less than 25% in this group."

"In contrast, eradication rates for OBMT [omeprazole, bismuth biskalcitrate, metronidazole, and tetracycline] and OAC [omeprazole, amoxicillin and clarithromycin] in metronidazole susceptible and metronidazole resistant strains were not significantly different and were over 80%."

Susceptibility testing of Helicobacter pylori for metronidazole has not been standardized. No interpretive criteria have been established for testing metronidazole against H. pylori.1 FDA has concluded that there is no way to determine metronidazole resistance or susceptibility.2

Compliance and Safety

"Compliance was comparable in the two study groups: 91% of patients in the OBMT group [omeprazole, bismuth biskalcitrate, metronidazole, and tetracycline] and 94% of patients in the OAC group [omeprazole, amoxicillin and clarithromycin] took at least 75% of their study medications."

"The most common adverse events were of a GI nature. Diarrhea was the most common adverse event and was nearly twice as frequent in the OAC group [omeprazole, amoxicillin and clarithromycin]."

Case Study Chart
* bismuth biskalcitrate 140 mg, metronidazole 125 mg, tetracycline 125 mg given
as 3 capsules q.i.d. plus omeprazole 20 mg b.i.d.

** omeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, all b.i.d.

First-Line Treatment

"Thus, this OBMT quadruple therapy [omeprazole, bismuth biskalcitrate, metronidazole, and tetracycline] with the single-triple capsule can be considered as a first-line regimen or treatment of H. pylori infection."

Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with metronidazole and requires treatment with an antifungal agent.

References
1. Ulcers and stress: Is there a connection? Mayo Clinic Website. Available at http://www.mayoclinic.com/health/peptic-ulcer/DS00242 Accessed 2/3/09 2. IMS Health November 2009.