Arthur A. Ciociola

Helicobacter pylori infection rates in duodenal ulcer patients in the United States may be lower than previously estimated

OBJECTIVES:Published studies have estimated the rate of Helicobacter pylori (H. pylori) infection in patients with duodenal ulcer disease to be as high as 95%; the majority of remaining duodenal ulcers have been attributed to the use of ulcerogenic drugs such as nonsteroidal antiinflammatory drugs (NSAIDs). We aimed to assess the H. pylori prevalence rates of U.S. duodenal ulcer patients in large, well-controlled studies.METHODS:More than 2900 patients with endoscopically diagnosed non-NSAID duodenal ulcers were enrolled in a series of six placebo-controlled, double-blind studies conducted in the United States that assessed H. pylori using a combination of tests. Patients were considered infected with H. pylori only if culture growth was observed, or both histological and CLOtest results were positive. Patients were considered uninfected if the results of at least two tests were negative. Patients with missing test results, results of only a single test, or conflicting test results were not evaluable for H. pylori assessment.RESULTS:Of the 2394 endoscopically diagnosed evaluable duodenal ulcer patients, 73% (1737) were confirmed infected with H. pylori at study entry.CONCLUSIONS:The results of six carefully designed and controlled studies suggest that an assumed H. pylori infection rate of approximately 95% may overestimate the actual rate of H. pylori infection in duodenal ulcer patients in the United States. Although H. pylori infection is an important factor in the etiology of noniatrogenic duodenal ulcer disease, other factors may predominate in some patients and should not be overlooked in determining an appropriate course of treatment. The empiric use of antibiotic therapy for ulcer patients without confirmation of the presence of H. pylori cannot be recommended.

Dual and Triple Therapy Regimens of Antisecretory Agents and Antibiotics for the Eradication of Helicobacter pylori: An Overview

BACKGROUND Studies evaluating therapeutic regimens that combine antisecretory agents with antibiotics for the eradication of H. pylori have reported significant variations in efficacy. METHODS We reviewed the published literature to compare H. pylori eradication rates in patients treated with either omeprazole, ranitidine bismuth citrate (RBC), or ranitidine plus metronidazole combined with either amoxicillin or clarithromycin. RESULTS Wide variations in H. pylori eradication rates have been reported with omeprazole plus either amoxicillin (0-100%) or clarithromycin (42-88%). Eradication rates ranging from 45% to 89% and from 74% to 94% have been reported with RBC plus either amoxicillin or clarithromycin, respectively. Eradication rates ranging from 48% to 90% have been reported with ranitidine plus metronidazole and amoxicillin and one study reported an eradication rate of 95% with ranitidine plus metronidazole and clarithromycin CONCLUSIONS Well-controlled trials with ranitidine bismuth citrate plus clarithromycin suggest that this combination may provide the most consistent and effective regimen for the eradication of H. pylori infection.

The FDA's Generic-Drug Approval Process: Similarities to and Differences From Brand-Name Drugs

The FDAs Generic-Drug Approval Process: Similarities to and Differences From Brand-Name Drugs

Effects of ranitidine bismuth citrate on gastric acid secretion and gastrin release in subjects with and without Helicobacter pylori infection

Background: Ranitidine bismuth citrate is a novel antiulcerant that provides the antisecretory activity of ranitidine and the gastric mucosal protection and antibacterial properties of bismuth.

Ranitidine Bismuth Citrate Plus Clarithromycin: A Dual Therapy Regimen for Patients with Duodenal Ulcer

The combination of ranitidine bismuth citrate (RBC) and clarithromycin (CLR) was compared with each treatment alone for the eradication of H. pylori and healing of duodenal ulcers in patients infected with H. pylori.

The Food and Drug Administration advisory committees and panels: how they are applied to the drug regulatory process.

Food and Drug Administration (FDA) advisory panels and committees play a critical role in advising the FDA on the safety and efficacy of medical devices and drugs marketed in the US. Advisory panel recommendations are used by the FDA to make decisions regarding medical products. Currently, the FDA utilizes over 50 advisory panels that serve the three major FDA centers, including the Centers for Biologics, Drugs and Device Products. Members of an advisory panel typically include academicians, clinicians, consumers, patients, and industry representatives. The FDA establishes the schedules for advisory panel meetings on an annual basis and a panel usually meets several times a year for two consecutive days in Washington, DC. Typically, the advisory panel discusses issues highlighted by the FDA and is then asked to vote a response to the questions posed in advance by the FDA. Advisory panel recommendations have a strong influence on FDAs decision to approve a product, as evidenced by the 214 Advisory Panels FDA convened between January 2008 to November 2012, during which advisory panel members voted to approve the product (or use of the product) ∼74% of the time, with FDA ultimately approving the medical product (or use of the product) ∼79% of the time. The ACG membership are encouraged to consider serving the publics interest by participating in an FDA advisory panel utilizing their expertise for the evaluation of a new drug or medical device, and providing advice about whether the product should be sold in the US.

Nonprescription Doses of Ranitidine Are Effective in the Relief of Episodic Heartburn

BackgroundMany Americans have heartburn or related symptoms monthly and >20% experience heartburn at least once per day. Although many self-treat episodic heartburn with nonprescription antacids, newer treatments that decrease gastric volume and increase the pH of refluxed material are proving effective and popular in relieving heartburn. AimTo evaluate the safety and efficacy of low-dose regimens of ranitidine for the relief of heartburn. Methods Adults with at least a 3-month history of heartburn were eligible for this randomized, double-blind, parallel group, multicenter dose-ranging study. Following a 1-week, open-label run-in phase to document baseline heartburn frequency, subjects were randomly assigned to receive treatment with one tablet of either ranitidine, 75 mg (n = 537); ranitidine, 25 mg (n = 539); or placebo (n = 544), to be taken as needed up to four times daily for 2 weeks for the relief of heartburn. ResultsThe ranitidine 75-mg regimen was statistically (P < 0.05) and clinically (as defined a priori as ≥10% improvement) more effective than placebo in relieving episodic heartburn and in reducing antacid consumption. Ranitidine, 25 mg, was also statistically superior (P < 0.05) to placebo in providing heartburn relief. In addition, both regimens were superior to placebo in providing heartburn relief within 30 to 45 minutes of dosing. Ranitidine continued to be as effective over placebo in the treatment of the last heartburn episode as in the treatment of the first heartburn episode. Ranitidine was also equally effective over placebo in the treatment of mild, moderate, and severe episodes of heartburn. Ranitidine, 75 mg, was statistically superior to placebo for the relief of nocturnal heartburn episodes, whereas ranitidine, 25 mg, was not. All treatments were well tolerated and adverse events occurred no more frequently with the ranitidine regimens than with placebo. ConclusionsLow-dose ranitidine provides prompt and lasting relief of heartburn and has a safety profile comparable to that of placebo.

An Alternative Non-Macrolide, Non-Imidazole Treatment Regimen for Curing Helicobacter pylori and Duodenal Ulcers: Ranitidine Bismuth Citrate Plus Amoxicillin

Background. Because patients who fail to be cured of H. pylori infection following macrolide or imidazole therapy are difficult to treat, there is a clear need for a reasonably effective and simple second‐line treatment regimen. The purpose of these two studies was to evaluate the efficacy of ranitidine bismuth citrate (RBC) plus amoxicillin for the cure of H. pylori infection and for healing duodenal ulcers and preventing ulcer relapse.

The continued use of placebo-controlled clinical trials in the study of peptic ulcer disease : A sponsor perspective

Investigators and institutional reviews boards who/which have participated in recent controlled gastroenterology clinical research studies assessing new therapies for peptic ulcer disease have questioned the continued use of a placebo-control when efficacious therapies for peptic ulcer disease are currently available. As the sponsor of such studies, Glaxo is of the opinion that the use of placebo-controlled clinical research studies is appropriate in certain situations. In choosing between the use of an active comparator or placebo-controlled trial Glaxo recommends an assessment of the severity of the disease and the morbidity associated with use of placebo treatment. It further recommends the need to assess the efficacy of placebo therapy to establish the baseline remission rate for the disease. Glaxo suggests an assessment of the safety data for the new chemical entity under investigation, and if such data are lacking, minimize patient risk employing suggested study designs that maximize patient utilization. The statistical implications of sample size and the risks associated with Type I and II errors by comparing the number of patients required for a typical study using a placebo and active control are discussed. Finally, for all placebo-controlled studies performed with patients with peptic ulcer disease, the elimination of high risk patients, the use of supplemental antacids, and proper obtainment of informed patient consent is recommended.