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.     

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.     

Antacid Treatment of Duodenal Ulcer

ABSTRACT. Becker U, Lindorff K, Andersen C, Ranløv PJ (Department of Internal Medicine B, Central Hospital, Hillerød, Denmark). Antacid treatment of duodenal ulcer. Acta Med Scand 1987; 221:95–101. Sixty-seven consecutive outpatients with endoscopically verified duodenal ulcer were randomised to a double-blind treatment with either 10 ml of an antacid suspension (buffering capacity 85 mmol/10 ml, packed in single dosage pads) 1 and 3 h after each meal and at bedtime or cimetidine 400 mg b.i.d. The double-dummy technique was employed. Endoscopy was performed after 4 weeks treatment and, if the ulcer had not healed, after 8 weeks treatment. When ulcer healing had occurred, the patient entered a 1 year follow-up study. The cumulative healing rates after 4 and 8 weeks treatment were 83 and 97% vs. 69 and 94% in the antacid and cimetidine groups respectively. No significant differences were observed between the treatment groups regarding ulcer healing, symptom relief or compliance. Adverse reactions were few and only 3 (9%) patients in the antacid group had to discontinue the treatment due to diarrhoea. Of the cimetidine treated patients, 61% had symptomatic relapse during the 1 year follow-up compared to 71% of the antacid treated patients. There were no significant differences in recurrence rate or time to relapse. The moderate dose antacid treatment used here is efficient, well tolerated, safe, convenient and is a good alternative treatment of the duodenal ulcer patient.     

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.     

Dynamism of cytoprotective and antisecretory drugs in patients with unhealed gastric and duodenal ulcers

Abstract A continuous multiclinical, randomized and prospective study has been carried out in our department to compare the efficacy of different cytoprotective (sucralfate, DE-NOL, Vitamin A) and antisecretory drugs (atropine, cimetidine, ranitidine, famotidine, pirenzepine) on ulcer healing in patients with chronic gastric ulcer (GU) and duodenal ulcer (DU).
A total of 441 patients were randomized in different groups. The patients were treated with atropine (1 mg/day), cimetidine (1000 mg/day), ranitidine (300 mg/day), famotidine (80 mg/day), pirenzepine (50 mg/day), sucralfate (1000 mg/day), Vitamin A (3 × 50 000 IU/day) alone or in combination with cyproheptadinum (3 × 4 mg/day) DE-NOL (3 × 5 mL/day) and Tisacid® (Al-Mg-hydroxycarbonicum; in different doses). Endoscopy (planimetric evaluation of ulcer sizes), measurements of clinical changes in patients' complaints, antacid consumption and laboratory tests (blood count, urine, kidney and liver functions, electrolytes, pH status) were carried out at the beginning and 2, 4 and 6 weeks after treatment with different drugs. The incidence of ulcers, changes of ulcer sizes, subjective pain score and antacid consumption were noted at the abovementioned times. There were 20 or more patients in each group. The dynamism of ulcer healing rate was studied on the unhealed GU and DU.
Our results showed that the ulcer size decreased significantly in all groups in GU and DU patients treated with cytoprotective and antisecretory drugs. Summed pain score (expressed as per cent of basic values) and antacid consumption decreased significantly in all groups. As well, some differences were found in the dynamism of ulcer healing at 2 weeks after the treatment. No significant differences were found in the dynamism of gastric and duodenal ulcers in patients treated with cytoprotective and antisecretory drugs at 4 and 6 weeks of 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.     

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.     

Duodenal ulcer healing with four antacid tablets daily

In a double-blind, randomized, multicenter trial in 80 consecutive outpatients with endoscopically verified duodenal ulcer, we have tested the ulcer-healing efficacy of a quite low dose of antacids, given only four times daily. The patients received one chewable aluminum-magnesium-antacid tablet (buffering capacity, 30 mmol/tablet) or placebo 1 h after meals and at bedtime. Re-endoscopy after 4 weeks of treatment showed healed ulcer in 28 of 38 patients (74%) in the antacid group, compared with 11 of 38 patients (29%) in the placebo group (p less than 0.001). The number of days and nights with ulcer pain was significantly less in the antacid group than in the placebo group during the treatment period. Thus, only four antacid tablets a day, with a total buffering capacity of 120 mmol/day, significantly promote duodenal ulcer healing and pain relief.     

Very-low dose antacid in treatment of duodenal ulcer

Antacid (AA) in a very low dose (88 mmol/day) was compared to the standard 800-mg dose of cimetidine in healing duodenal ulcers. The influence of sex, age, symptom duration at entry, night pain, smoking, coffee consumption, and alcohol on ulcer healing was studied. The antacid was given in two different schedules: group I--20 ml 1 hr after breakfast and at bedtime; group II--10 ml 1 hr after breakfast and lunch and 20 ml at bedtime. Cimetidine (group III) was given in two divided doses: 400 mg 1 hr after breakfast and 400 mg at bedtime. Endoscopic control was performed after four weeks and, if necessary, after eight weeks of treatment. The healing rate after four weeks of treatment was, respectively, for groups I, II, and III, 45.5%, 55.8%, and 69.4% (group I = group II, and group III different from groups I and II). After eight weeks of treatment the healing rate was 61.5%, 80.8%, and 88.0% for groups I, II, and III, respectively (group II = group III, and group I different from groups II and III). Except for group I, smoking did not influence healing rate. Age, sex, symptoms at entry, night pain, and coffee consumption did not influence the treatment results. The authors concluded that the very low dose of magaldrate (88 mmol/day), when administered in three divided doses (10 ml after breakfast and lunch and 20 ml at bedtime) for eight weeks was as effective as 800 mg of cimetidine (400 mg twice a day) in healing duodenal ulcer.     

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.     

Comparison of ranitidine and high-dose antacid in the treatment of prepyloric or duodenal ulcer. A double-blind controlled trial

One hundred and nineteen patients with endoscopically confirmed prepyloric (n = 59) or duodenal (n = 60) ulcer were stratified for ulcer location before entering a randomized double-blind trial comparing ranitidine (150 mg twice daily) and a potent liquid antacid (Novaluzid; 10 ml seven times daily, with a neutralizing capacity of 600 mmol H+). Fifty-four patients with prepyloric (26 receiving ranitidine) and 53 patients with duodenal ulcer (28 receiving ranitidine) completed the trial in accordance with the protocol. The 4 and 6 weeks' healing rates for prepyloric ulcers were 54%, 68%, and 61%, versus 69%, 79%, and 74% for the ranitidine, the antacid, and whole groups, respectively. For duodenal ulcers these figures were 89%, 84%, and 87%, versus 100%, 96%, and 98% for the ranitidine, antacid, and whole groups, respectively. Differences in healing rates between treatments were statistically insignificant within strata for ulcer type, but healing rates for prepyloric ulcers were significantly lower than for duodenal ulcers (p less than 0.002). A significant early pain relief was found in all groups, and side effects, including diarrhoea, were rare. In conclusion, these two ulcer treatment modalities appear to be equally effective in the short term. In addition, the data emphasize the need for proper stratification of prepyloric and duodenal ulcers in clinical trials of ulcer healing.     

Maintenance therapy for duodenal ulcer: a randomized controlled comparison of seven forms of treatment.

PURPOSE: We performed a randomized controlled trial to compare the efficacy of seven forms of maintenance treatment of duodenal ulcer, including a mealtime regimen of antacids. PATIENTS AND METHODS: We randomized 785 patients with healed duodenal ulcer to receive: (1) no treatment; (2) mealtime antacids with an acid-neutralizing capacity of 80 mmol/day; (3) an antidepressant, trimipramine 25 mg; (4) an anticholinergic, pirenzepine 50 mg; (5) cimetidine 200 mg; (6) cimetidine 400 mg; (7) ranitidine 150 mg; or (8) sucralfate 1 g twice a day. Symptomatology and side effects were assessed every 2 months and endoscopy was performed every 4 months up to 1 year. RESULTS: The patients were comparable in the majority of clinical characteristics before entry. The cumulative percentages of patients with relapse of ulcers at 12 months by life-table analysis were 61% with no treatment, 38% with mealtime antacids, 60% with trimipramine, 52% with pirenzepine, 46% with cimetidine 200 mg, 44% with cimetidine 400 mg, 30% with ranitidine 150 mg, and 40% with sucralfate. Cimetidine 400 mg, antacids, ranitidine 150 mg, and sucralfate were significantly better than no treatment and the other forms of treatment. Ranitidine was significantly better than antacids, cimetidine, and sucralfate in preventing endoscopically documented duodenal ulcer relapse by multiple comparison at 12 months, but not by life-table analysis nor when symptomatic relapses were compared. No significant difference was detected among antacids, cimetidine, and sucralfate. No major side effects occurred with the seven forms of treatment, but those receiving antacids had the highest incidence of minor adverse events (26%). CONCLUSION: This study suggests that mealtime antacids are as effective as H2-receptor antagonists and sucralfate in the maintenance treatment of duodenal ulcer disease, but have to be taken three times a day and had the highest incidence of reported minor adverse events. The relapse rate was lower with ranitidine than with cimetidine, sucralfate, and antacids, but the difference was small and may not be clinically important.     

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.     

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.     

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.     

Ranitidine in the treatment of duodenal ulceration

In a randomized, double-blind, endoscopically controlled clinical trial, 40 patients with duodenal ulcer were treated with either ranitidine (320 mg/day) or cimetidine (800 mg/day) for 28 days. The rate of healing of the ulcers (ranitidine, 78%, cimetidine, 45%) did not differ significantly in the two treatment groups. In a subsequent 'open' study, ranitidine (150 mg twice daily) healed the ulcers of 79% of 19 patients treated for 28 days. Treatment with ranitidine was not associated with significant adverse reactions and had no lasting effect on gastric secretory capacity. Whereas basal levels of serum testosterone rose significantly during treatment with cimetidine, no such increase was observed during treatment with ranitidine. We conclude that ranitidine can effectively and safely heal duodenal ulcers.     

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.     

Long-term low-dose antacid versus cimetidine therapy in the treatment of duodenal ulcer recurrence

The effect of cimetidine (400 mg at night) and of low-dose antacid (400 mg of aluminum hydroxide plus 400 mg of magnesium hydroxide four times a day) given alone or in combination was assessed in a double-blind double-dummy endoscopic trial on prevention of duodenal ulcer (DU). Seventy-five outpatients with healed DU were followed up clinically for 1 year and were checked endoscopically after 6 and 12 months of therapy or in case of symptomatic relapse. After 6 and 12 months, 25% and 41%, respectively, of patients treated with cimetidine alone experienced a relapse, compared with 42% and 54% of those treated with antacid alone and 25% and 43% of patients treated with the combination therapy. The differences are not statistically significant. No relevant side effects were observed in patients of any group. It is concluded that long-term prophylactic treatment of DU with low-dose antacid is as safe and effective as cimetidine treatment, whereas a combination of the two drugs does not achieve a therapeutic gain.     

Effects of antiulcer agents on healing of mepirizole-induced duodenal ulcers in rats

Healing processes of duodenal ulcers induced by mepirizole and effects of several drugs on the ulcer healing were studied in rats. Mepirizole-induced duodenal ulcers, except for the perforated ones within 3 days after ulceration, gradually diminished in size and depth by the 15th day. Several ulcers persisted for up to 40 days, but complete healing in all rats occurred by the 60th day after ulceration. Oral cimetidine and YM-11170 (both histamine H2-receptor antagonists), at 200 and 30 mg/kg twice daily for 10 days, respectively, significantly accelerated the healing of duodenal ulcers. Oral Maalox (antacid) at 1,000 mg/kg thrice daily and propantheline (anticholinergic agent) at 30 mg/kg twice daily tended to accelerate the healing of the ulcers. Oral 16,16-dimethyl PGE2, at 0.03 and 0.1 mg/kg twice daily, resulted in a delayed healing of the ulcers. Mepirizole-induced duodenal ulcers appear to be a useful model for the study of ulcer healing and for screening of antiulcer drugs.     

Effect of no treatment, cimetidine 1 g/day, cimetidine 2 g/day and cimetidine combined with atropine on nocturnal gastric secretion in cimetidine non-responders

We have studied nocturnal acid secretion in patients with duodenal ulcer who met predetermined criteria of poor clinical response to cimetidine. Different groups of patients were investigated receiving either no treatment, cimetidine 1 g/day, cimetidine 2 g/day or cimetidine 1 g/day combined with atropine 4.8 mg/day. The results were compared with those obtained from other patients with duodenal ulcer who were studied in our department but who were not classified as according to their clinical response to cimetidine. The results show that despite adequate absorption, cimetidine has a decreased effect at controlling acid secretion in the poor responders and that increasing the dose of drug does not improve response. Control of acid output was, however, dramatically improved when cimetidine was combined with atropine which suggests that patients who do not respond to H2-receptor blockade should be treated by a combination of cimetidine with an anticholinergic agent.