Comparison of cimetidine and pirenzepine in the healing and maintenance of remission in duodenal ulcer

The effect of cimetidine and pirenzepine on the maintenance of healing in duodenal ulceration has been compared in a multi-centre, controlled study. One hundred and sixty-six patients with endoscopically proven duodenal ulceration have been randomised to receive either cimetidine 200 mg t.i.d. and 400 mg nocte, or pirenzepine 50 mg b.i.d. for 6 weeks. Patients in each group were well matched for age, sex, weight and cigarette, alcohol and antacid consumption. After 6 weeks significantly more cimetidine-treated patients had healed ulcers: cimetidine showed 8 unhealed out of 79, and pirenzepine 19 out of 74 (p = 0.01). The follow-up phase lasted for 52 weeks or until patient withdrawal or ulcer relapse. During the follow-up phase 77.6% of cimetidine-treated and 68.8% of pirenzepine-treated patients relapsed. This difference in relapse rates is not statistically significant (p = 0.23).     

Cimetidine or propantheline combined with antacid therapy for short-term treatment of duodenal ulcer

Seventy-one patients with duodenal ulcer disease completed a 3-to 6-week controlled randomized trial in which cimetidine (1 g daily) was compared with an optimally effective dose of propantheline. Both groups had free access to an antacid suspension. There were no significant differences between the groups concerning ulcer healing, relief of ulcer symptoms, antacid consumption, or patient compliance. After 3 weeks of treatment, endoscopic examination revealed complete ulcer healing in 63% of the cimetidine and 47% of the propantheline treated patients. The corresponding figures after 6 weeks were 94% and 86%, respectively. After 12 weeks, ulcer recurrence was confirmed in 26% of the cimetidine-and 23% of the propantheline-treated patients. Except for the absence of anticholinergic adverse reactions, no significant advantages could be confirmed, for combined cimetidine and antacid treatment.     

Effect of antacids on the bioavailability and therapeutic efficacy of cimetidine

Five patients with duodenal ulcer received cimetidine and after an interval of four days cimetidine with antacid. Cimetidine in serum was analysed with high performance liquid chromatography. There was no significant difference in the values of the pharmacokinetic parameters of cimetidine (Cmax, tmax and AUC) when taking cimetidine alone and cimetidine plus antacid. 53 outpatients with endoscopically proven duodenal ulcer were evaluated in a randomized study, so as to compare the therapeutic effect of cimetidine and aluminum hydroxide gel plus cimetidine. 18 of 26 patient taking cimetidine alone (69.2%) and 19 of 27 patients taking cimetidine plus antacid (70.4%) had their ulcer completely healed after 4 weeks. The overall healing rates after 8 weeks for the groups taking cimetidine alone and cimetidine plus antacid were 80.0% and 92.6% respectively with no significant difference. This study indicates: (1) Simultaneous administration of aluminum hydroxide gel does not alter the bioavailability of cimetidine. (2) Combined administration of aluminum hydroxide gel and cimetidine does not alter the therapeutic effect of cimetidine in patients with duodenal ulcer.     

Comparative study of cimetidine and Mylanta II in the 6-week treatment of gastric ulcer

The efficacy of antacid in the treatment of benign gastric ulcer is less well established than in the treatment of duodenal ulcer. The objective of this study was to monitor ulcer healing and symptom relief in 38 patients with gastric ulceration treated for 6 weeks with cimetidine (Tagamet) 300 mg q.i.d. or an aluminum-magnesium containing antacid (Mylanta II) 10 ml q.i.d. (acid neutralizing capacity 203.2 mEq/day). The study was single-blind; the study physicians and those providing endoscopic assessments were not aware of the patients' treatment. Entered into the study were 19 male and 19 female patients ranging in age from 17 to 70 years, with a mean age of 52 years. None of the patients had taken cimetidine in the previous month, and none abused alcohol or nonsteroidal anti-inflammatory agents, but two-thirds of the patients were smokers. Five patients in the antacid group withdrew for numerous reasons including continued pain, noncompliance, and side effects. All patients in the cimetidine group completed the study, and no side effects were noted. There was no difference between the antacid- and the cimetidine-treated patients in the relief of symptoms. There was a significant difference in the 6-week ulcer healing between the groups, with 14/19 (74%) healed in the cimetidine group compared with only 6/14 (43%) healed in the antacid group (p less than 0.025). Thus, Mylanta II, 10 ml four times daily, is comparable to cimetidine 300 mg q.i.d. in the symptomatic relief of benign gastric ulceration, but ulcer healing was superior using cimetidine.     

Medium-dose antacids versus cimetidine in the short-term treatment of duodenal ulcer

Seventy-eight patients with endoscopically proven duodenal ulcer were randomly allocated to be treated with a medium dose of liquid aluminum-magnesium antacid (75 ml in five daily doses) or cimetidine (400 mg twice daily) for 4 weeks in a prospective double-blind, double-dummy study. Healing rates at completion of trial were 66.7% in the cimetidine-treated group and 71.8% in the antacid group (p, ns). Both treatments were equally effective in relieving ulcer symptoms. Among the patient variables considered, only cigarette smoking was found to have a significant negative effect on ulcer healing. These results indicate that medium doses of antacids are as effective as cimetidine in the short-term treatment of duodenal ulcer.     

Cimetidine vs placebo in duodenal ulcer therapy

We studied the healing efficacy of cimetidine or placebo in 23 endoscopically proven duodenal ulcer outpatients in a randomized, controlled, prospective, double-blind trial. There were 11 patients in the cimetidine (1200 mg daily) treatment group and 12 patients in the placebo-treated group. No antacid was allowed, but a placebo antacid with no neutralizing capacity was given as needed for pain. The incidence of complete endoscopic healing at 2, 4, and 6 weeks was 54%, 63%, and 72% in the cimetidine-treated patients and 8%, 50%, and 67% in the placebo-treated patients. There was a statistically significant difference (P<0.05) in complete duodenal ulcer healing between both treatment groups after 2 weeks of therapy, but there was no significant difference at the 4- and 6-week observation periods. The incidence of complete pain relief at 2 and 4 weeks was 64% and 82% in the cimetidine-treated patients and 67% and 75% in the placebo-treated patients. At 6 weeks of treatment there was no increase in the number of patients with complete pain relief in either group. There was no significant difference between the two groups in the incidence of ulcer pain relief at any of the three observation periods. Duodenal ulcer healing rates and duodenal ulcer pain relief were compared at 2, 4, and 6 weeks. There was no statistical association between ulcer healing and complete pain relief in the placebo treatment group at the 2-week evaluation period, but there was statistical association (P<0.05) in the cimetidine treatment group at 2 weeks and both treatment groups at the 4- and 6-week evaluation periods. The results of this study demonstrate that in duodenal ulcer outpatients treated for 6 weeks: (1) cimetidine increases the incidence of duodenal ulcer healing during the first 2 weeks of treatment; (2) more than 50% of duodenal ulcers will spontaneously heal during a 4 to 6-week observation period which is not statistically modified by cimetidine treatment; (3) the complete relief of duodenal ulcer pain is not influenced by treatment with cimetidine when compared to placebo.     

Recurrent ulcer after successful treatment with cimetidine or antacid

This study was designed to compare the rates of duodenal ulcer healing and recurrence after treatment with cimetidine or antacid. Patients with endoscopically documented duodenal ulcer received cimetidine, 1200 mg daily, or Mylanta II, 7 oz daily, in a randomized, double-blind trial. For the 69 patients in each group who completed the healing phase of the trial, endoscopic ulcer healing was almost identical. At 2, 4, and 6 wk, the cumulative percent healed on antacid was 33%, 64%, and 80%, and on cimetidine it was 25%, 62%, and 86%. The 114 patients with healed ulcer were observed on no therapy and underwent additional endoscopy to detect recurrences when symptomatic or at 3, 6, and 12 mo. There was no difference in the frequency of recurrences between treatments. At 3 and 6 mo, the cumulative percentages of patients with recurrence were 29% and 56% after antacid therapy and 36% and 55% after cimetidine therapy. Some patient variables were associated with delayed ulcer healing or ulcer recurrence. These included sex, pain frequency, smoking, disease duration, and acid secretion.     

Low-dose antacids or cimetidine for duodenal ulcer?

In a double-blind, randomized, multicenter trial 150 consecutive outpatients with endoscopically verified duodenal ulcer were treated with either a low-dose antacid regimen (1 tablet q.i.d.; acid-neutralizing capacity, 120 mmol/day), or cimetidine (800 mg nocte). After 4 wk of treatment control gastroscopy showed ulcer healing in 54 of 76 patients (71.1%) in the antacid group, as compared with 58 of 74 patients (78.4%) in the cimetidine-treated group. The difference in healing rate of 7.3% (95% confidence interval, -6.5% to +21.1%) was not statistically significant. The symptomatic effect, measured as number of days and nights with ulcer pain, was also quite similar in the two treatment groups. However, the number of days with pain was significantly lower in the first week of treatment in the antacid group (p less than 0.01). Thus, the efficacy of a low-dose antacid tablet regimen approximated that of cimetidine (800 mg nocte) in the treatment of duodenal ulcer patients.     

Controlled therapeutic trial to determine the optimum dose of antacids in duodenal ulcer

Antacids are widely used in the management of duodenal ulcer but the optimum dose of antacid required for ulcer healing has not been determined. We therefore studied 107 patients with endoscopically diagnosed duodenal ulcer who were allotted at random to one of the following treatment groups; placebo (group P) and antacid (groups A, B and C). A liquid antacid (Aludrox MH, Wyeth) with neutralising capacity of 2.3 mmol HCl/ml was administered in graded doses of 7.5 ml (Group A), 15 ml (Group B), and 30 ml (Group C), one hour and three hours after each meal, six times a day for four weeks. Patients in group P received 15 ml liquid placebo in a similar fashion. Complete symptomatic relief was obtained in 33% of patients in the placebo group, 54% in antacid group A, 89% in group B, and 92% in group C. Endoscopic assessment at the end of four weeks of treatment gave an ulcer healing rate of 29% in the placebo group, 46% in group A (103.5 mmol antacid/day), 85% in group B (207 mmol/day), and 88% in group C (414 mmol/day). There was no significant difference in the healing rates and pain relief between placebo and antacid group A, while both groups B and C had significantly higher ulcer healing rates and pain relief compared with placebo (p less than 0.001) and antacid group A (p less than 0.01). Drug related unwanted effects were recorded only in group C - 28% of patients suffered from diarrhoea. It is concluded that the optimum antacid requirements for the treatment of duodenal ulcer is 90 ml (acid neutralising capacity, 207 mmol HCl) per day.     

Comparison of cimetidine and tripotassium dicitrato bismuthate in healing and relapse of duodenal ulcers

A comparison between cimetidine and tripotassium dicitrato bismuthate liquid (TDB) in the treatment of endoscopically diagnosed duodenal ulcer by single-blind randomized trial in 48 patients has shown 18 (75%) out of 24 patients receiving TDB and 13 (54%) out of 24 patients receiving cimetidine healed after 4 weeks' therapy. Symptomatic improvement within 1 month was seen in 19 patients on TDB and 18 patients on cimetidine, but did not only occur in patients whose ulcers healed. On follow-up, endoscopically proven relapse occurred within 1 year in 47% of patients whose ulcers had healed during treatment with TDB in comparison with 60% of those healing on cimetidine.     

Relapse rates of duodenal ulcer healed with concentrated antacid or cimetidine

The incidence of duodenal ulcer relapse after initial therapy with concentrated aluminium-magnesium hydroxide (Maalox 70) or cimetidine (Tagamet) was investigated in a one-year follow-up study. 92.3% (24 out of 26) of the antacid patients and 76.2% (16 out of 21) of the cimetidine patients relapsed. The difference is not statistically significant. With respect to the pattern of onset of relapses, no difference was seen between the two groups. 33% of the recurrent lesions following treatment with antacids and 25% of those following cimetidine therapy were asymptomatic. This difference too is not significant. The results permit the conclusion that the mode of pharmaceutical therapy of ulcers (buffering of gastric acid by way of an antacid or inhibition of acid secretion by an H2-blocker) has no bearing on the further course of the ulcer disease.     

The use of ranitidine in the management of duodenal ulcer: controlled and open comparison with cimetidine in 59 patients

Forty patients with duodenal ulcer were randomly allocated either ranitidine 150 mg twice daily or cimetidine 1 g daily on a single blind basis for 4 weeks initially, with an additional month of treatment if endoscopy showed incomplete healing. The endoscopist was unaware of the patients' treatment. After 8 weeks treatment, the healing rate was 85% for ranitidine and 95% for cimetidine; the difference was not statistically significant. An additional 19 patients who did not fulfill the trial criteria, 11 of whom had not responded to cimetidine, were openly treated with ranitidine 150 mg twice daily. In 16 of the patients, the ulcer had healed at 8 weeks (84%), but in one patient, the ulcer perforated after 6 weeks of therapy. Thus, although overall healing rates with ranitidine and cimetidine are similar, ranitidine may be useful in patients where cimetidine has proved ineffective.     

Double blind comparison between cimetidine and gefarnate in cases of duodenal ulcer.

Thirty outpatients suffering from duodenal ulcer of recent onset were given cimetidine 1 g/day or gefarnate 250 mg/day for 6 weeks in a double blind trial, randomly balances between the groups. Endoscopic assessment was carried out at 4 and 6 weeks; patients healed after 4 weeks were withdrawn from the trial. In all parameters considered, cimetidine showed a highly significant difference. The healing rate at 4--6 weeks was 67--93% after cimetidine treatment and 27--53% after gefarnate treatment. The effect of cimetidine on the disappearance of symptoms, mainly the nocturnal ulcer pain, and on antacid consumption was greater than that after medication wity gefarnate. After 4--6 weeks of a full dose cimetidine regimen, both basal and pentagastrin stimulated gastric acid secretion were reduced and peptone meal stimulated serum gastrin increased; the basal gastrinaemia remained unchanged.     

Gastric ulcer recurrence: follow-up of a double-blind, placebo-controlled trial

Following a multicenter, double-blind trial comparing cimetidine, antacid, and placebo for the treatment of gastric ulcer, patients whose ulcers had healed were followed prospectively to assess the frequency of ulcer relapse. Fifty-eight patients entered the follow-up study. Patients were encouraged to discontinue smoking and excessive ethanol intake, but were not maintained on antiulcer medications. Clinical evaluation was performed at monthly intervals; repeat endoscopy was performed at the time of symptom recurrence or at 6 to 9 months after ulcer healing. Gastric ulcer recurred in 20 of 58 patients (35%). While 15 (75%) with ulcer recurrence had symptoms, 5 (25%) had asymptomatic recurrences. There were no differences in the incidence of ulcer relapse or symptom recurrences between groups. We conclude that gastric ulcers recur in approximately one-third of patients within 9 months of ulcer healing.     

Endoscopic double-blind controlled trial of ranitidine vs placebo in the short-term treatment of duodenal ulcer

The aim of the present study was to investigate the effectiveness of ranitidine in the treatment of duodenal ulcer. Fourty patients with endoscopically proven pyloric or duodenal ulcer were treated with ranitidine 40 mg t.d. with meals and 80 mg nocte, or identical placebo tablets under double-blind conditions. Endoscopy after four weeks of treatment revealed complete healing in 15 out of 18 (83.3%) ranitidine-treated patients and in 5 out of 17 (29.4%) of the placebo patients (P less than 0.01). Ulcer symptoms were significantly less in ranitidine-treated patients, while the difference in antacid consumption between the two groups was found to be only arithmetical. No side effects or significant hematological or biochemical abnormalities were found. Four-week treatment with 200 mg of ranitidine daily seems to correspond to that of 6-8 weeks with 1-1, 6 g of cimetidine.     

Famotidine versus cimetidine in the treatment of acute duodenal ulcer. Double-blind, randomized clinical trial comparing nocturnal administration of 40 mg famotidine to 800 mg cimetidine

The efficacy of famotidine, a potent new long-acting H2 receptor antagonist, was compared with cimetidine in 78 patients with endoscopically proven acute duodenal ulcers. Additional antacid self-medication was allowed if needed for relief of pain. Thirty-nine patients were allocated to each group, receiving a nocturnal oral dose of either 40 mg famotidine or 800 mg cimetidine. Patients were reassessed by endoscopy at 2, 4 and 6 weeks if ulcer healing had not occurred at the respective earlier control date. A diary was kept to record the duration and intensity of day and night pain and the amount of antacids ingested. After 2 and 4 weeks of treatment healing rates were not significantly different for either group (famotidine 31 and 95%, cimetidine 23 and 85%, respectively). Pain relief was rapid in both treatment groups with a tendency for better response of nighttime pain in famotidine-treated patients. Antacid consumption was not different in either group. Famotidine appears to be an effective treatment for acute duodenal ulcer. Compared to cimetidine, healing rates and relief of pain are not significantly different.     

Short-term treatment of prepyloric ulcer

A double-blind, randomized, multicenter study was performed to compare the effect of sucralfate (1 g qid) and cimetidine (400 mg bid) in the treatment of prepyloric ulcer. Altogether 142 patients (68 in the sucralfate and 74 in the cimetidine group) with endoscopically confirmed ulcer within 2 cm of the pylorus completed the study. Endoscopic follow up was performed after four weeks and, if the ulcer was not healed, after eight weeks of treatment. After four weeks, 65% of the ulcers in the sucralfate group were healed, compared to 70% in the cimetidine group. There was no significant difference between sucralfate and cimetidine at either time point. The 95% confidence interval for the difference in ulcer healing with sucralfate or cimetidine ranged from +4 to –19% at eight weeks. Said another way, with an observed difference of 7% (83% vs 90%), the 95% confidence limit ranged from 4% in favor of sucralfate to 19% in favor of cimetidine. Symptomatic relief, antacid intake, and side effects did not differ significantly between the two groups. The healing rate of prepyloric ulcer in this study is similar to that reported for duodenal ulcer after four and eight weeks when treated with sucralfate or cimetidine. Sucralfate is safe and as effective as cimetidine in the short-term treatment of prepyloric ulcer.     

Are endoscopic and/or histologic findings in gastroduodenal mucosa a predictor of clinical outcome in peptic ulcer disease? A 1-year follow-up study after initial healing with either cimetidine or medium-dose antacid

Patients with duodenal ulcer (DU; n = 79) or prepyloric ulcer (PPU; n = 39) received cimetidine, 400 mg twice daily, or Novaluzid, 10 ml four times daily (acid-neutralizing capacity, 340 mmol/day), in a multicentre, randomized, double-blind trial. Ulcer healing was almost identical with the two treatments at 4, 6, and 12 weeks in the DU group. Cimetidine was significantly more effective than antacids in alleviating symptoms in PPU disease, with no significant difference in ulcer healing. In the PPU group the symptomatic improvement was inferior irrespective of treatment, and there was a significantly lower healing rate at 4 weeks (p less than 0.05) than in the DU group. The relapse rate over a 1-year follow-up period with no therapy did not differ between the two treatment groups or between the two ulcer groups. No factors in history of disease or endoscopic or histologic variables were of predictive value with regard to delayed healing. The macroscopic appearance of the duodenal and antral mucosae improved significantly when ulcers had healed. In the subgroup of about 50% DU patients who experienced a relapse during the 1-year follow-up period, the histologic scoring of duodenitis remained basically unchanged, contrary to the significant improvement seen in the non-relapsing subgroup. The microscopic changes of the antral mucosa from the time of inclusion to healing seen in the PPU patients were of no predictive value with regard to relapse rate.     

A controlled study comparing cimetidine treatment to an intensive antacid regimen in the therapy of uncomplicated duodenal ulcer

The authors report the results of a randomized study in which comparison was made between two different kinds of treatment in patients affected by uncomplicated duodenal ulcer endoscopically diagnosed. The first group was treated with 1 g of cimetidine per day, during a period of four weeks (200 mg three times a day and 400 mg at bedtime); the second with a liquid Al–Mg antacid compound, 210 ml/day (30 ml, 1 and 3 hr after meals and 30 ml before bedtime) for four weeks. Fifty-one patients were studied, 27 treated with cimetidine, 24 with antacids. At the end of the four-week period, 21 patients (77.7%) in the cimetidine group and 18 patients (75%) in the antacid group were completely healed. Benign side effects were remarked in both types of treatment, none of which made it necessary to suspend treatment. No significant variation of the basal and peak acid output before and after each kind of treatment was observed, while a slight but significant increase in fasting serum gastrin concentration was noted after treatment in the antacid group.     

Comparison of relapse rates and of mucosal abnormalities after healing of duodenal ulceration and after one year's maintenance with cimetidine or sucralfate: a light and electron microscopy study.

Forty six patients with endoscopically diagnosed duodenal ulceration were randomly allocated to treatment with either sucralfate 1 g qds (n = 24) or cimetidine 200 mg tds and 400 mg nocte (n = 22). When the ulcers healed, a maintenance dose of sucralfate 1 g bd or cimetidine 400 mg nocte was given for one year (or until relapse if earlier). Biopsies of duodenal mucosa adjacent to ulcer sites for light and electron microscopy were obtained before and after healing and again after one year's maintenance if the ulcer remained healed. Duodenal biopsies were also taken from 20 age and sex matched controls. Rates of healing and relapse during maintenance did not differ between the two treatments, although relapses occurred earlier with cimetidine. In the three year post-maintenance follow up period 10/13 cimetidine patients relapsed compared with four of 11 sucralfate patients (p less than 0.05), the relapses occurring significantly earlier in the cimetidine treated patients (p less than 0.05). Mucosal biopsies from both treatment groups still showed considerable abnormalities after healing. During maintenance, however, the sucralfate scores fell significantly (p less than 0.02) to near control levels unlike the cimetidine scores which remained raised at pretreatment values. The histological and ultrastructural changes were not predictive of later relapse. These findings favour the use of sucralfate in preference to cimetidine for maintenance treatment in the prevention of relapse of healed duodenal ulcers.