Changes of gastric histology in patients with erosive oesophagitis receiving long-term lansoprazole maintenance therapy.

BACKGROUND: Changes in gastric histology associated with long-term maintenance therapy with lansoprazole for erosive oesophagitis have not been well described. AIM: To evaluate the effect on gastric histology of long-term dose-titrated lansoprazole administered as maintenance therapy for up to 82 months in patients with erosive oesophagitis. METHODS: Sequential gastric biopsy specimens were obtained for evaluation of histological changes and Helicobacter pylori infection status. RESULTS: Active and chronic inflammation improved from baseline to final visit in a majority of patients receiving long-term therapy with lansoprazole, irrespective of baseline H. pylori infection status. Reductions in active inflammation in the gastric body and antrum were seen in 53% (17/32) and 67% (20/30) of H. pylori-positive patients, respectively, and in 88% (7/8) and 86% (12/14) of H. pylori-negative patients, respectively. Reductions in chronic inflammation in the gastric body and antrum were seen in 38% (12/32) and 47% (15/32) of H. pylori-positive patients, respectively, and in 58% (70/121) and 57% (68/120) of H. pylori-negative patients, respectively. No clinically meaningful increases in hyperplasia, dysplasia, neoplasia, intestinal metaplasia or atrophy were observed during the follow-up period. CONCLUSIONS: Lansoprazole administered as maintenance therapy for up to 6 years in patients with erosive oesophagitis demonstrated gastric mucosal safety and was well tolerated.

The clinical safety of long-term lansoprazole for the maintenance of healed erosive oesophagitis.

BACKGROUND: The clinical safety of long-term lansoprazole therapy for the maintenance of healed erosive oesophagitis has not been extensively studied in clinical trials. AIM: To assess the long-term clinical safety of dose-titrated lansoprazole as maintenance therapy for up to 82 months in subjects with healed erosive oesophagitis. METHODS: Clinical safety was assessed by monitoring adverse events (AEs), laboratory data including serum gastrin levels, and endoscopy. RESULTS: Mean duration (+/- s.d.) of lansoprazole treatment during the titrated open-label period was 56 +/- 24 months (range <1-82 months). Overall, 189 of 195 (97%) subjects experienced a total of 2825 treatment-emergent AEs. Most AEs occurred during the first year of treatment, were mild-to-moderate in severity and resolved while on treatment. Of 155 serious AEs (in 74 subjects), only two (colitis and rectal haemorrhage in one subject) were considered treatment-related. Sixty-nine of 195 subjects (35%) experienced 187 treatment-related AEs, with diarrhoea (10%), headache (8%) and abdominal pain (6%) being the most common. Gastrin levels > or = 400 pg/mL were seen in 9% of subjects; hypergastrinemia was not associated with gastro-intestinal AEs or nodules/polyps. CONCLUSIONS: Lansoprazole maintenance therapy for up to 6 years is safe and well tolerated in subjects with healed erosive oesophagitis.

Rating the severity of the medical consequences of drug-induced liver injury.

Risk analysis in drug development aims to allow for clear decisions showing whether or not the benefit of an intervention outweighs the risk. One of the difficulties in doing this in a repeatable and clear way is the problem of comparing different adverse events, as seriousness is often subjective. Using drug-induced liver injury as our model, we show that clinical, laboratory, and histological manifestations of liver reactions can be ranked by experienced hepatologists and these rankings can be used to rank the consequences of drug-induced side effects as a continuum. This risk ranked information could be transformed to standardized scores (z score) and the risks displayed by standard techniques; adverse events can then be compared with effects from other drugs and possibly with the consequences due to untreated disease or natural occurrences. As a risk is a function of both the seriousness of the event and the probability of its occurrence, risk can therefore be displayed in terms of probability and hazard to further ease communication. We propose that risk management of drugs in development would be improved, especially in terms of risk communication, if the hazard were ranked by means of a common scale and displayed in graphic form against the likelihood of occurrence.

A novel option in proton pump inhibitor dosing: lansoprazole orally disintegrating tablet dispersed in water and administered via nasogastric tube.

BACKGROUND: Lansoprazole orally disintegrating tablet, which rapidly disintegrates on the tongue or in water, provides a dosing alternative for patients with difficulty in swallowing. Gastric and nasogastric tubes are increasingly placed in patients with more severe swallowing disorders. AIM: This study assessed the pharmacokinetic profile of lansoprazole orally disintegrating tablet dispersed in a small volume of water and administered through a small-bore nasogastric tube. METHODS: Forty healthy adult men and women (18-43 years) received two single 30 mg lansoprazole orally disintegrating tablet doses (one administered directly onto the tongue without water, and one dispersed in water and administered via nasogastric tube) in a randomized, crossover fashion. RESULTS: The total plasma exposure to lansoprazole was comparable following both dosing regimens; mean AUC values for the lansoprazole orally disintegrating tablet nasogastric dispersion were < or =8.6% greater than those for the intact lansoprazole orally disintegrating tablet. Lansoprazole Cmax for the lansoprazole orally disintegrating tablet nasogastric dispersion was 20.9% greater than that for the intact lansoprazole orally disintegrating tablet, a difference of no clinical significance. CONCLUSIONS: Dispersion of the lansoprazole orally disintegrating tablet in a small volume of water and administering via nasogastric tube does not reduce the pharmacokinetic profile of the intact lansoprazole orally disintegrating tablet. This alternative dosing method may be useful in patients with nasogastric or gastric tubes.

Evaluation of the pharmacokinetics and pharmacodynamics of intravenous lansoprazole.

AIM: To compare the pharmacokinetics and pharmacodynamics of lansoprazole 30 mg administered intravenously in 0.9% NaCl or in polyethylene glycol, or orally. METHODS: Twenty-nine subjects received lansoprazole orally on days 1-7 and intravenous lansoprazole in NaCl on days 8-14. Blood samples were collected on days 1, 7, 8 and 14. Fasting basal acid output and pentagastrin-stimulated maximal acid output were determined on days -1, 8, 9 and 15. Thirty-six different subjects received one of four regimen sequences: intravenous lansoprazole in NaCl, intravenous in polyethylene glycol, per orally, or intravenous placebo, each for 5 days. Twenty-four hour intragastric pH was recorded on days 1 and 5. RESULTS: Intravenous and per oral lansoprazole for 7 days produced equivalent basal acid output and maximal acid output suppression. Pharmacokinetics and mean pH values with intravenous lansoprazole in NaCl or polyethylene glycol were equivalent. Both produced mean pH and percentages of time pH above 3, 4, 5 and 6 that were significantly greater than did per orally. CONCLUSIONS: Intravenous lansoprazole inhibits acid secretion as effectively in NaCl as in polyethylene glycol, and its onset of action is faster than per oral lansoprazole.

Review article: approaches to the long-term management of adults with GERD-proton pump inhibitor therapy, laparoscopic fundoplication or endoscopic therapy?

The goals of gastro-oesophageal reflux disease (GERD) treatment are to control symptoms, heal the injured oesophageal mucosa, and prevent complications. Pharmacological therapy is effective in producing acute symptom relief and mucosal healing, as well as the long-term maintenance of remission. Proton pump inhibitors are the mainstay of GERD therapy. However, the need for daily administration, failure to provide complete symptom relief and costs of these agents may limit their use in some patients, prompting a consideration of alternative treatment strategies. Laparoscopic fundoplication may achieve symptom relief and healing of the oesophagitis in these individuals, but its invasiveness, cost and inherent surgical risks have created an interest in endoscopic therapies for GERD, with several emerging during the past few years. These interventions may either be viewed as an alternative therapy or as 'bridge' therapy, with patients still choosing to be treated with acid anti-secretory drugs or fundoplication if the endoscopic procedure fails to provide adequate symptom relief or if symptoms recur. Patient selection is critical for the success of fundoplication as well as endoscopic procedures, with ideal candidates being those with well-established endoscopically documented GERD, abnormal pH monitoring, normal oesophageal motility studies, and who have experienced at least partial symptom relief with proton pump inhibitor therapy. Hiatal hernia is not a contra-indication to fundoplication, while endoscopic intervention is best suited for those with a hiatal hernia of less than 3 cm in length. The long-term efficacy, cost-effectiveness, and impact of endoscopic procedures on extra-oesophageal manifestations of GERD and risk for GERD-related complications has not been determined.

Comparative pharmacokinetics and safety of lansoprazole oral capsules and orally disintegrating tablets in healthy subjects.

BACKGROUND: Many individuals with acid-related gastrointestinal disorders have difficulty in swallowing oral agents. AIM: To compare the bio-availability of a single dose of lansoprazole orally disintegrating tablet with that of an intact capsule. METHODS: One hundred and twenty healthy subjects participated in two prospective, Phase I, open-label, two-period cross-over studies to receive lansoprazole, 15 mg or 30 mg. Within each study, subjects were randomized into two parallel cohorts consisting of 30 subjects per regimen, dispensed in opposing sequence over two periods separated by a 7-day washout period. Blood samples were collected on day 1 of both periods to determine the pharmacokinetic parameters. RESULTS: Tmax occurred at 1.8 and 2.0 h with the 15-mg and 30-mg tablets, respectively. Dose proportional increases in Cmax, AUCt and AUC infinity were observed in the 15-mg and 30-mg groups. The terminal elimination half-lives (t1/2) were identical in both dose groups (1.18 h). Lansoprazole administered as the orally disintegrating tablet was bio-equivalent to the intact capsule formulation with respect to Cmax, AUCt and AUC infinity. CONCLUSIONS: Lansoprazole orally disintegrating tablets, 15 mg and 30 mg, are bio-equivalent to the respective dose administered as the intact capsule. This novel dosage formulation represents an option for patients who have difficulty in swallowing oral agents.

Review article: role of proton pump inhibitors in non-H. pylori-related ulcers.

The proportion of ulcers that are not associated with Helicobacter pylori infection is increasing, especially in the United States and Australia. The alarming increase in this type of ulcer warrants an analysis of the diagnostic and treatment approaches to H. pylori-negative ulcers, which was the aim of this study. The medical literature was reviewed to gather information about the prevalence, aetiology, and treatment of H. pylori-negative ulcers. The reports indicated that up to 52% of duodenal ulcers and 47% of gastric ulcers are not caused by H. pylori infection. The cause of H. pylori-negative ulceration appears to be multifactorial. Contributing factors include covert non-steroidal anti-inflammatory drug use, false-negative H. pylori tests, genetic predisposition, and in rare cases, Crohn's disease or Zollinger-Ellison syndrome. H. pylori-negative ulcers tend to be associated with hypersecretion and can have serious clinical sequelae. H. pylori-negative ulcers are often refractory to treatment, possibly because they lack the beneficial effect of H. pylori infection on antisecretory therapy. Proton pump inhibitors (PPIs) appear to effectively treat both H. pylori-positive and H. pylori-negative ulcers. We conclude that H. pylori-negative ulcers are becoming more prevalent in the United States and Australia. These ulcers may have an aggressive clinical course and can be refractory to treatment. PPI therapy is indicated for treating and preventing H. pylori-negative peptic ulcers.

Management of heartburn in a large, randomized, community-based study: comparison of four therapeutic strategies.

OBJECTIVE: Our objective was to compare four management strategies for heartburn: therapy with an H2-receptor antagonist (ranitidine), therapy with a proton pump inhibitor (lansoprazole), crossover from ranitidine to lansoprazole ("step-up" therapy), and crossover from lansoprazole to ranitidine ("step-down" therapy). METHODS: This was a controlled, double-blind, multicenter trial comprising 593 adults with heartburn, randomized to one of four groups for 20 wk. Subjects received either ranitidine 150 mg b.i.d. for 20 wk, or lansoprazole 30 mg once daily for 20 wk, or ranitidine 150 mg b.i.d. for 8 wk [corrected] followed by lansoprazole 30 mg once daily for 12 wk ("step-up"), or lansoprazole 30 mg once daily for 8 wk followed by ranitidine 150 mg b.i.d. for 12 wk ("step-down"). Outcome measures were based on self-reports in daily diaries of 24-h heartburn severity, measured by maximum daytime and nighttime severity, and percentage of 24-h heartburn-free days measured by absence of both daytime and nighttime heartburn. RESULTS: Median heartburn severity was significantly lower (p < 0.05) for lansoprazole (0.25) than the other groups (0.46 ranitidine, 0.44 "step-up," 0.35 "step-down"). The lansoprazole group had a significantly higher percentage of 24-h heartburn-free days (median 81.4%, p < 0.01) than other groups (66.6, 66.9, and 73.6%, respectively). In the "step-up" and "step-down" groups, heartburn was less severe, and percentages of 24-h heartburn-free days were higher during lansoprazole treatment regardless of treatment sequence. CONCLUSION: Proton pump inhibitor treatment provides more consistent heartburn relief than an H2-receptor antagonist, or "step-up" or "step-down" therapy.

Attributable risk of H. pylori in peptic ulcer disease: does declining prevalence of infection in general population explain increasing frequency of non-H. pylori ulcers?

Recent reports in the United States have found that fewer peptic ulcers are due to Helicobacter pylori than previously believed. The aim of this study is to determine if the declining prevalence of H. pylori infection in the general population can account for the apparent increase in the frequency of non-H. pylori ulcers. A total of 396 patients with peptic ulcer or ulcer scar were enrolled in this study. The pre-1950 population consisted of 149 patients with gastric ulcers and with 44 duodenal ulcers. The post-1950 population consisted of 96 patients with gastric ulcers and 107 with duodenal ulcers. The frequency of H. pylori-negative gastric ulcers was 5.4% in patients born before 1950 and 4.2% in patients born after 1950, and the frequency of H. pylori-negative duodenal ulcers was 0% and 1.9%, respectively. There are no statistical differences between the two populations in gastric and duodenal ulcers. H. pylori seropositivity was 74.9% in asymptomatic volunteers born before 1950 and 20.7% in those born after 1950 (P < 0.01) in the general population. The attributable risk of H. pylori infection in peptic ulcer diseases was not affected by the prevalence of H. pylori infection in the general population in Japan. This suggests that the apparent increase in frequency of non-H. pylori ulcers in the United States is not simply due to the declining prevalence of infection. Other explanations for non-H. pylori ulcers should be sought.

Helicobacter pylori-negative peptic ulcers: frequency and implications for management.

Most patients with peptic ulcers are infected with Helicobacter pylori, but the infection may not be responsible for the ulcer. It is increasingly recognized that different causes of ulcers coexist in a given patient, confounding determination of the exact cause of the ulcer. For example, in infected patients with ulcers who also are using nonsteroidal anti-inflammatory drugs (NSAIDs), it is not possible to establish the ulcer's cause. Moreover, recent studies in the United States in infected patients with duodenal ulcers who were treated with various regimens to prove their efficacy in eradicating H. pylori and preventing ulcer recurrence found that approximately 20% of patients suffered an ulcer recurrence despite successful H. pylori eradication. The infection clearly did not cause their ulcers but was originally thought to have done so. Thus, as many as one-fifth of patients with ulcers may have the cause falsely attributed to H. pylori infection. When this number is added to that of ulcer patients who are H. pylori-negative upon original presentation--at least 20% in other recent U.S. studies--it is evident that the proportion of non-H. pylori ulcer patients is larger than originally believed. This proportion is likely to increase with the declining incidence of H. pylori infection. Other causes of ulcers include the use of aspirin and NSAIDs (which may be surreptitious), hypersecretory states, Crohn's disease, and patients with "idiopathic" ulcers. Patients with "idiopathic" ulcers are characterized by postprandial hypersecretion of acid and hypergastrinemia with accelerated gastric emptying. H. pylori ulcers may be difficult to manage because antisecretory drugs are less effective in inhibiting gastric acidity in the absence of H. pylori infection.

Management of peptic ulcers: emerging issues.

Most peptic ulcers are caused by Helicobacter pylori infection. The infection is best diagnosed by a radiolabeled carbon urea breath test, which also can prove that eradication therapy was successful. Serologic testing is useful for establishing prior or present infection but not to determine if the infection has been eradicated. Endoscopic tests usually are not needed to establish a diagnosis. Modern ulcer treatment consists of H. pylori eradication in infected patients. A combination of a proton pump inhibitor plus clarithromycin and amoxicillin or a proton pump inhibitor plus bismuth, metronidazole, and tetracycline are the most effective regimens. Reinfection is less than 2% per year in developed countries. Evidence suggests that H. pylori eradication may foster the development of erosive esophagitis, but confirmatory studies are needed. Studies also suggest an interaction between H. pylori infection and peptic ulcers related to the use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the studies are conflicting: One shows that H. pylori eradication protects against NSAID-related ulcers; another suggests protection afforded by the infection. Non-H. pylori peptic ulcers remain a challenge, especially in the United States, where one study showed that 42% of peptic ulcers were not due to the infection. Some non-H. pylori ulcers are refractory to usual doses of antisecretory drugs.

Safety profile of Lansoprazole: the US clinical trial experience.

OBJECTIVE: Lansoprazole has undergone extensive clinical evaluation for the treatment of acid-peptic diseases. The aim of this study was to define the safety profile of lansoprazole and compare it to that of other therapeutic agents evaluated in the same controlled trials. METHODS: The clinical safety profile of lansoprazole and comparative agents (placebo, ranitidine and omeprazole) was reviewed for 3281 patients who participated in short term (up to 8 weeks) and long term (up to 56 months) clinical trials conducted in the US. Adverse events, laboratory value changes and gastric biopsy changes that occurred during treatment were compared statistically for differences between treatments. RESULTS: The incidence of adverse events and number of patients discontinuing treatment because of adverse events was similar for lansoprazole and comparative agents. Other than elevated serum gastrin levels, a known effect of proton pump inhibitors, no trends in laboratory changes were observed. Median values for gastrin levels remained within the normal range; about 2% of patients had gastrin levels >400 pg/ml at any time, while <1% had 2 or more gastrin values >500 pg/ml. Values returned to baseline levels after therapy was discontinued. No significant changes in gastric endocrine cell growth from baseline to final visit were observed, nor was there evidence of dysplasia or neoplasia. CONCLUSION: Lansoprazole is well tolerated for both short and long term treatment of acid-related disease. The tolerability of lansoprazole is comparable to that of ranitidine, omeprazole and placebo in the treatment of these diseases.

Rationalizing cyclooxygenase (COX) inhibition for maximal efficacy and minimal adverse events.

New information indicates that cyclooxygenase-2 (COX-2) is constitutively expressed in several tissues, including brain, lung, pancreas, kidney, and ovary, and plays an important role in renal and gastrointestinal function. Selective COX-2 inhibition has been associated in animal studies with impairment of ulcer healing and renal function and inhibition of prostacyclin, an effect that inhibits vasodilation without inhibiting platelet aggregation. The clinical consequences, if any, of these effects remain to be determined in long-term studies in humans. The premise that selective COX-2 inhibitors will cause less gastrointestinal toxicity than nonsteroidal antiinflammatory drugs that inhibit both COX isoforms needs to take into account the low toxicity of nabumetone. The gastrointestinal safety profile of this nonacidic, dual COX inhibitor that does not undergo enterohepatic circulation has been evaluated in extensive clinical trials. The data submitted to the US Food and Drug Administration in the New Drug Application for nabumetone (Relafen), the comparative trials subsequently completed, the published databases of the comparative gastrointestinal toxicity of various nonsteroidal anti-inflammatory drugs (NSAIDs), and the meta-analysis published in this issue of The American Journal of Medicine (Schoenfeld, page 48S) indicate that nabumetone has the lowest incidence of gastrointestinal toxicity among the extensively studied NSAIDs. Overall, the incidence is approximately 10-fold less than with comparator drugs. This rate is an appropriate current reference against which the gastrointestinal toxicity of COX-2 inhibitors can be compared.

What remaining questions regarding Helicobacter pylori and associated diseases should be addressed by future research? View from North America.

Several areas regarding Helicobacter pylori that need improvement or clarification in the United States include treatment of dyspepsia, physician education on disease associations with H. pylori, and evidence from U.S. studies that 7-day H. pylori eradication regimens are more effective than current regimens. Dyspepsia, a ubiquitous condition in the United States, is routinely managed on the basis of a positive H. pylori serology without other investigations. This approach has been fostered by cost-effectiveness studies of various approaches to duodenal ulcer and dyspeptic patients. Serology-directed therapy was the most cost-effective option vs. endoscopy-directed management. The option of not obtaining endoscopy had broad appeal to primary care physicians. In addition, a recent survey suggests that even gastroenterologists routinely attempt H. pylori eradication in infected patients with nonulcer dyspepsia, despite a number of negative efficacy studies. Finally, the option of not eradicating a World Health Organization-defined carcinogen in the litigious United States is unappealing to clinicians. Eradication of H. pylori in patients with dyspepsia despite more negative trials is likely to continue. There is evidence that U.S. physician awareness of the H. pylori-disease associations and the best therapies are improving rapidly, but further improvement is needed. Discrepancy of awareness of H. pylori between gastroenterologists and family physicians exists. In a recent survey, 94% and 72% of gastroenterologists regarded H. pylori as a causative agent in duodenal and gastric ulcer, respectively, vs. 68% and 68% of family physicians, and only 9% of family physicians believed there was a definite relationship between H. pylori infection and gastric cancer vs. 21% of gastroenterologists. One hundred three different H. pylori regimens were being used; 31% of family physicians and 11% of gastroenterologists used ineffective regimens or regimens of unknown effectiveness. Although 1-week proton pump inhibitor triple therapy is promising, there is skepticism that U.S. studies will yield the optimistic results that have characterized the European studies. Unlike in Europe, the U.S. standard is to use double diagnostics to prove eradication rather than just the urea breath test and to use intent-to-treat rather than assessable patient analyses. Both approaches reduce apparent eradication rates.

Review and analysis of the effects of olestra, a dietary fat substitute, on gastrointestinal function and symptoms.

Olestra, a dietary fat substitute, was recently made available to consumers in savory snacks in three cities. Early reports of gastrointestinal complaints attributed to olestra attracted media coverage and fostered confusion among physicians and consumers about the nature of olestra and its effects on the digestive system. We reviewed all published studies of olestra's gastrointestinal effects and all relevant unpublished studies submitted to the Food and Drug Administration. Each study was analyzed by a group of expert gastroenterologists and epidemiologists. The symptoms reported with olestra ingestion are similar to those reported with ingestion of fiber and sorbitol, although the mechanisms involved in changing stool characteristics differ among these food additives. Olestra's effects on stool habit and characteristics are due to its presence in the stool. Large amounts are more likely to induce gastrointestinal symptoms than small amounts. There is no evidence that olestra induces pathological change in bowel function: there is no increased fluid or electrolyte nor is there altered gastrointestinal motility or microflora. Olestra and triglyceride ingestion resulted in a similar frequency of symptoms in normal adults and children and in people with chronic inflammatory bowel disease in remission. Olestra traverses the digestive tract intact to become a stool additive. Some subjects develop a change in bowel habit and stool characteristics due to the presence of more olestra in the stool. These changes resemble those associated with ingestion of sorbitol and fiber.

Long-term acid control and proton pump inhibitors: interactions and safety issues in perspective.

Concerns have been raised regarding the safety of proton pump inhibitors in the long-term management of acid-related peptic disease, especially with regard to the physiological effects of prolonged hypochlorhydria. Of special consideration is the potential for development of enterochromaffin-like cell hyperplasia and gastric carcinoids, colorectal adenocarcinoma and polyps, and bacterial overgrowth as a result of achlorhydria. However, the magnitude of hypergastrinemia associated with the administration of proton pump inhibitors is comparable to that observed after vagotomy and is 3- to 6-fold lower than that observed with pernicious anemia. Only minimal morphological changes in gastric endocrine cells have been observed after the long-term daily administration of proton pump inhibitors, and these changes appear to be self-limiting, nondysplastic, and nonneoplastic. All current evidence suggests that the hypergastrinemia observed during proton pump inhibitor therapy has little clinical significance. However, longer-term results are necessary so that one can appreciate the full implications of acid suppression by proton pump inhibitors.

Pharmacoeconomic comparison of treatments for the eradication of Helicobacter pylori.

BACKGROUND: Patients with Helicobacter pylori-induced duodenal ulcer should have their infection eradicated. The optimal choice of antibiotic therapy, however, is less clear. OBJECTIVE: To evaluate costs and outcomes of treatment with 8 antibiotic regimens with documented activity against H pylori vs maintenance therapy with histamine2-receptor antagonists (H2RA). METHODS: A meta-analysis for 119 studies enrolling 6416 patients to determine aggregate eradication rates. The complexity of each regimen was used to determine the anticipated compliance rate and actual effectiveness. A decision analytic model with Monte Carlo simulation determined annual costs and health outcomes. RESULTS: Average annual total costs of testing for H pylori infection and antibiotic treatment ranged from $223 to $410 and prevented ulcer recurrence in 70% to 86% of patients. The H2RA maintenance therapy cost $425 and prevented recurrence in 72% of patients. The lowest costs and recurrence rates were achieved by 3 regimens: standard triple therapy (a combination of bismuth subsalicylate, metronidazole, and tetracycline hydrochloride) for 14 days ($223, with 18% recurrence); a combination of clarithromycin, metronidazole, and a proton pump inhibitor for 7 days ($235, with 15% recurrence); and standard triple therapy with a proton pump inhibitor for 7 days ($236, with 14% recurrence). CONCLUSION: Treatment with any regimen resulted in lower costs compared with H2RA maintenance therapy. Three antibiotic regimens had consistently lower costs and better outcomes: standard triple therapy for 14 days, metronidazole, clarithromycin, and a proton pump inhibitor for 7 days, and standard triple therapy plus a proton pump inhibitor for 7 days.