Some Days 3 Drugs R Best; Some Days its 4 Drugs
Maybe the best news is that we have two choices to treat H. Pylori
3-Drug Regimen for H pylori Superior in Latin America
July 21, 2011 — Despite data from North America, Europe, and Asia indicating that newer 4-drug regimens show superiority in the eradication of Helicobacter pylori infection than standard triple–oral antibiotic regimens, new findings from a randomized trial in Latin America indicate that the standard regimen is a more effective treatment in this setting, according to findings reported online July 20 in The Lancet.
H pylori, which accounts for an estimated 60% of cases of gastric cancer around the world, is commonly treated with a standard 3-drug regimen of a proton pump inhibitor combined with amoxicillin and clarithromycin, taken over the course of 7 to 14 days.
An emerging resistance to clarithromycin, however, is believed to be diminishing the effectiveness of the therapy. Recent meta-analyses of trials in Europe, Asia, and North America suggest that the addition of a nitroimidazole (metronidazole or tinidazole) to the regimen, given either sequentially for 10 days or concomitantly for 5 days, is significantly more effective in eradicating the infection.
In an effort to compare the efficacy of the 2 therapies in Latin America, where rates of H pylori infection and gastric cancer mortality are among the world’s highest, E. Robert Greenberg, MD, from the Southwest Oncology Group Statistical Center, Cancer Research and Biostatistics, Seattle, Washington, and colleagues enrolled 1463 participants who tested positive for H pylori at 7 Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and 2 sites in Mexico.
Between September 2009 and June 2010, participants were randomly assigned to receive the 14-day, standard, 3-drug therapy of lansoprazole, amoxicillin, and clarithromycin (n = 488); the 5-day concomitant therapy of the 3 drugs plus metronidazole (n = 489); or a sequential therapy of 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (n = 486).
The study was not masked, and the eradication of H pylori was determined by a urea breath test 6 to 8 weeks after randomization.
Using intention-to-treat analysis, the probability of eradication with the standard therapy in the study population was 82.2% (401/488), which was 8.6% higher than the 73.6% seen with concomitant therapy (360/489; 95% adjusted confidence interval [CI], 2.6 – 14.5) and 5.6% higher than the 76.5% rate seen with sequential therapy (372/486; 95% adjusted CI, −.04 to 11.6).
The findings were consistent at all 7 sites, in which neither of the 4-drug regimens showed superiority in eradication over the standard triple therapy.
From an economical standpoint, the researchers hypothesized that the 4-drug regimens would be favorable for eradication programs in low-resource settings because they require fewer antibiotic doses than the 3-drug regimens. However, their findings do not support improved efficacy in the setting studied.
“Our principal outcome measure, the probability of H. pylori eradication, was higher for 14-day standard triple therapy than for both 4-drug regimens, and these results did not vary significantly by age, sex, study site, or history of chronic dyspeptic symptoms,” the authors write.
“Our results are important because they challenge those of meta-analyses showing that 4-drug regimens (triple therapy plus a nitroimidazole) given concomitantly or sequentially were clearly better than triple therapy, and they suggest that findings based primarily on data from Europe and other high-income regions might not be readily generalisable to lower-income countries.”
Previous meta-analyses looking at other regions showed eradication probabilities with the 5-day concomitant and 10-day sequential regimens to be higher than 90% compared with less than 80% in the current study, and the researchers speculated that the difference may be explained by drug resistances that could be more developed in some regions than others.
“Geographical variations in the pattern of H. pylori resistance to antibiotics might account for some of the discrepancies between the results,” they write.
Although Dr. Greenberg and colleagues assert that the findings of their trial suggest that implementation of population-wide H pylori elimination trials throughout Latin America to prevent gastric cancers caused by the infection is feasible, the authors of an accompanying editorial disagree.
“Policies aimed at population-wide H. pylori eradication could have individual and social repercussions,” write Luiz Edmundo Mazzoleni, MD, from the Universidade Federal do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil, and colleagues.
Among the concerns that Dr. Mazzoleni and colleagues discuss are anaphylaxis from amoxicillin, increased mortality from clarithromycin in those patients with ischemic heart disease, and the possibility of Clostridium difficile infection from use of any antibiotic.
“Even if infrequent, these complications could become important [and life threatening] when eradicating H pylori at a population level,” they assert.
“Mass eradication is a major issue requiring further investigation…[it] is potentially feasible but in view of the differing socioeconomic realities of Latin American countries, doubts remain about the advisability of such a policy,” the physicians warn.
The study was supported by the Bill & Melinda Gates Foundation and the National Institutes of Health. Study coauthor Douglas R. Morgan, MD, MPH, from the University of North Carolina, Chapel Hill, has submitted a patent application for a technique using molecular endoscopy to detect cancer in the gastrointestinal tract and has received funding from Axcan for his participation in a speakers’ bureau. He has also received a research grant from AstraZeneca for a proton-pump inhibitor study in Hispanic populations in the United States, and from Given Imaging for ongoing efficacy studies of colon endocapsule efficacy. All other authors and the editorialists have disclosed no relevant financial relationships.