Concurrent Pancreatic Ductal Changes in Alcoholic Liver Disease
Background and Aim: Little is known about the clinical efficacy of cotherapy of ecabet sodium, a mucoprotective agent, and a histamine H2-receptor antagonist. The aim of the present study was to assess its additive benefit in combination with cimetidine for gastric ulcer.
Methods: In this prospective randomized study, after gastric ulcer was confirmed by endoscopy, 200 patients in 47 hospitals received either ecabet sodium 1 g b.i.d and cimetidine 400 mg b.i.d. (EC), or cimetidine 400 mg b.i.d. alone (C) for 8 weeks. Healing was examined by endoscopy at 4 and 8 weeks.
Results: Of the intention-to-treat (ITT) population (EC, 103; C, 97), 181 patients comprised the per protocol (PP) analysis (EC, 93; C, 88). At 4 weeks, healing rates were significantly higher in the EC group (60%) than in the C group (36%) ( p < 0.01). At 8 weeks, those by the ITT and PP analyses were 82% (EC) versus 58% (C), and 90% (EC) versus 64% (C), respectively ( p < 0.01 and p < 0.001). Symptom relief rates (EC vs C) at 2, 4 and 8 weeks were 73%versus 47% ( p < 0.01), 89%versus 66% ( p < 0.001), and 97%versus 73% ( p < 0.001), respectively. Significant additive effects of ecabet sodium were observed in patients aged 60 years or older, with solitary and medium to large ulcer, and without smoking or drinking habits. No adverse effects were critical.
Conclusion: Ecabet sodium significantly augmented gastric ulcer healing and symptom relief by cimetidine, especially in the elderly.
Gastric ulcer is one of the most common gastrointestinal tract diseases worldwide. Acid suppression has been accepted as the most reliable and effective treatment for gastric ulcer. While pepsin, acid, and Helicobacter pylori (H. pylori) are thought to be major factors in the pathophysiology of peptic ulcer diseases, the importance of the mucosal defense system has been emphasized. Production of mucin and prostaglandins (PG), as well as maintained mucosal blood flow, plays an important role in protecting the gastric mucosa from various kinds of irritants and maintaining the mucosal integrity. The effectiveness of gastroprotective agents, in fact, has been proved based not only experimental models but also on clinical trials. The more the mechanism of the mucosal defense system has been clarified, the more mucoprotective agents have been developed and prescribed in Japan. Although it would be reasonable to employ both an acid suppressant and a mucoprotective agent to treat gastric ulcer, few clinical trials have been carried out to examine the efficacy of cotherapy.
Ecabet sodium (ecabet, Gastrom, Tanabe Seiyaku Co. Ltd, Osaka, Japan), 12-sulfodehydroabietic acid monosodium salt, belongs to the category of gastroprotective agents; it exhibits a protective property on the gastric mucosa involving endogenous PG and nitric oxide (NO) synthesis, and increases blood flow in the gastric mucosa. It facilitated epithelial restitution of the bullfrog gastric mucosa in vitro following injury by hypertonic NaCl. Furthermore, ecabet significantly suppressed the activity of pepsin in human gastric juice, and protected the polymeric structure of mucus glycoproteins from proteolytic degradation by pepsin. Ecabet also sticks to the surface of the mucosa and enhances mucin metabolism, indicating its potential in strengthening the mucous barrier.
It has been shown that both ecabet and cimetidine, a histamine H2 receptor antagonist (H2-RA), inhibited the formation of aspirin-induced gastric mucosal lesions in rats. In this model, interestingly, a combination of ecabet and cimetidine demonstrated an antiulcer effect more remarkably than either drug alone. To our knowledge, there has been only one clinical report examining the additive effect of a mucoprotective agent, sucralfate, in combination with a H2-RA, resulting in the demonstration of no such benefit.
In Japan, ecabet has been used with a H2-RA for patients with gastric ulcer expecting the aforementioned mucoprotective effects. However, no reports have proved the additive benefit of ecabet. This lack of evidence prompted us to explore the effectiveness of ecabet in a prospective randomized comparative study. This is the first report to show the additive effect of ecabet in combination with a H2-RA in achieving ulcer healing and symptom relief in humans.
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