A multicenter, randomized, double-blind study comparing famotidine with cimetidine in the treatment of active duodenal ulcer disease

The efficacy and safety of famotidine (40 mg at night), a new potent H2-receptor antagonist, has been studied in 119 patients by four investigators in four Spanish hospitals in a randomized double-blind comparative study with cimetidine (800 mg at night). Antacid tablets were allowed as additional treatment, if needed for pain relief. There were no significant differences between the groups in baseline characteristics, including duodenal ulcer size. Efficacy parameters included daytime and nocturnal symptom relief and duodenal ulcer healing, documented by endoscopy, and defined as complete reepithelization of the ulcer crater. Endoscopy was performed at baseline and after 4 and 6 weeks of treatment. One hundred and five patients fulfilled the evaluation criteria (51 patients in the famotidine group and 54 in the cimetidine group). After 4 weeks, in 91.6% of the patients receiving famotidine and 82.3% of the patients receiving cimetidine ulcers were healed. After 6 weeks, healing rates were 96% (famotidine) and 85.1% (cimetidine) (p = 0.056). Pain relief was rapid in both treatment groups, with a tendency to better response during the day in the famotidine group. The intake of antacids, as well as the clinical and laboratory safety profile were similar for both groups.     

A multicenter, randomized, double-blind study comparing once-daily bedtime administration of famotidine and ranitidine in the short-term treatment of active duodenal ulcer

The efficacy and safety of famotidine and ranitidine in the treatment of active duodenal ulcer were compared in a multicenter, randomized double-blind study. The study was carried out at 5 centers and involved a total of 143 patients with endoscopically documented active duodenal ulcer. The patients received either famotidine (1 40 mg tablet at night) or ranitidine 2 150 mg tablets at night). Endoscopic examinations were performed at 4 and 6 weeks of active treatment. Day and nocturnal pain were also monitored, and the laboratory and clinical profiles evaluated. One hundred and thirty-three patients fulfilled the evaluation criteria (66 patients in the famotidine group and 67 in the ranitidine group). Healing rates at weeks 4 or 6 of treatment showed no significant differences between the famotidine group and the ranitidine group. The healing rates were 78% at week 4 and 96% at week 6 in the famotidine group, and 76% at week 4 and 95% at week 6 in the ranitidine group. Similar results were observed in both treatment groups with regard to pain resolution, decrease in antacid intake and safety profile.     

Famotidine versus ranitidine in the acute treatment of duodenal ulcer. A multicenter comparative study in Germany

185 patients with endoscopically proven duodenal ulcers were randomly allocated to treatment with either famotidine 40 mg nocte, 20 mg bid, 40 mg bid or ranitidine 150 mg bid for 2-8 weeks in a prospective double-blind study. The four groups were similar with regard to age, sex, duration of ulcer disease, smoking habits etc. After 2 weeks treatment 28/42 patients (66.7%) healed on famotidine 40 mg nocte, 24/42 patients (57.1%) on famotidine 20 mg bid, 26/41 patients (63.4%) on famotidine 40 mg bid and 28/43 patients (65,1%) on ranitidine 150 mg bid. The corresponding healing rates after 4 weeks were 90.5%, 83.3%, 90.2% and 93%, respectively. After 8 weeks more than 93% of the patients had healed ulcers. At each time there was no statistical difference between the different famotidine regimens and the ranitidine group. All treatments were well tolerated and severe adverse events were rare. Famotidine 40 mg at night, therefore, appears to be as good as conventional ranitidine.     

A randomized trial comparing cimetidine to nasogastric suction in acute pancreatitis

Clinical and experimental evidence has suggested that the use of cimetidine might be harmful to patients with acute pancreatitis. We conducted a randomized study comparing cimetidine to nasogastric (NG) suction in 95 patients with 103 episodes of mild to moderately severe, acute or relapsing pancreatitis (86.4% alcohol related). The groups were comparable on entry to the study, and daily evaluation of several clinical and laboratory criteria revealed no consistent differences between the two groups. When these same criteria were evaluated for time of return to normal, if abnormal on entry to the study, no differences were found. The cimetidine group had a significantly shorter stay in the hospital than did the NG group (6.8±2.7 vs 8.5±4.8 days). Neither the incidence of relapse or complication nor the duration and extent of hyperamylasemia were significantly different between patients treated with cimetidine or NG suction. We conclude that cimetidine is safe to use in patients with mild to moderately severe alcohol-related pancreatitis, but it offers minimal advantage over NG suction.     

A multicenter, double-blind, randomized, placebo-controlled comparison of nocturnal and twice-a-day famotidine in the treatment of active duodenal ulcer disease

The efficacy and safety of famotidine, a potent new long-acting H2-receptor antagonist, was compared with placebo in a multicenter, double-blind, randomized, placebo-controlled study in the United States. A total of 384 patients with endoscopically proven acute duodenal ulcer disease were enrolled. Patients received either famotidine or a placebo. The patients receiving famotidine were treated with one of three dose regimens, 40 mg h.s., 40 mg b.i.d., or 20 mg b.i.d. Patients were reassessed by endoscopy at 2, 4, and 8 wk if ulcer healing had not occurred sooner. A diary was kept to record the duration and intensity of the day and night pain and the amount of Gelusil antacid (Parke-Davis, Morris Plains, N.J.) ingested. Three hundred sixty-three patients met the evaluation criteria. The results revealed a 4-wk healing rate of 70%, 75%, 67%, and 31% for the famotidine 40 mg h.s., 40 mg b.i.d., 20 mg b.i.d., and placebo groups, respectively. The 8-wk healing rates for the same respective groups were 83%, 82%, 82%, 45%. Ulcer pain and antacid consumption occurred less often in the famotidine groups. The clinical and laboratory safety profile of the famotidine groups was similar to that of the placebo group. Famotidine appears to be an effective and safe once-a-day therapy for the treatment of acute duodenal ulcer disease. The recommended dosage is 40 mg h.s.     

Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy.

Hepatic encephalopathy due to cirrhosis is frequently precipitated by exogenous factors, and the effectiveness of a specific treatment with neomycin sulfate has so far not been submitted to clinical trials. Over a period of five years, 102 cirrhotic patients developed hepatic encephalopathy at admission or during hospitalization, and 39 were randomized for treatment with either neomycin sulfate or placebo. Exclusion criteria were: 1. current usage of specific treatment for hepatic encephalopathy, 2. chronic hepatic encephalopathy and 3. multiple organ failure syndrome associated with hepatic encephalopathy. The group of excluded patients (n = 63) was compared with the randomized group (n = 39), and no statistical differences were found regarding sex and age distributions, Child-Pugh classification, etiology of cirrhosis, percipitating factors and grade of hepatic encephalopathy. These same parameters were also comparable among the 20 patients who received active neomycin and the 19 who were treated with placebo. The therapy for hepatic encephalopathy consisted in the control of precipitating factors associated with 6 g of neomycin sulfate "per os" or placebo. Therapeutic failure and death by the fifth day of treatment, occurred in four patients (10.2%), two in each of the randomized groups. The time elapsed between the initiation of the therapeutic procedure and regression to grade zero of hepatic encephalopathy was 39.11 +/- 23.04 hours for the group of active neomycin, and 49.47 +/- 21.92 hours for the placebo group, but this difference did not achieve statistical significance.     

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.     

Randomized double-blind clinical trial of aluminum phosphate versus ranitidine in the acute treatment of duodenal ulcer

A randomized double-blind clinical trial of aluminum phosphate versus ranitidine in the treatment of noncomplicated acute duodenal ulcer has been conducted in 91 patients. After randomization the 42 patients of the aluminum phosphate group were comparable to the 49 patients of the ranitidine group. At 4 weeks, 6 patients were not endoscoped and according to the intention-to-treat method they were considered as treatment failure. The endoscopy showed a 60% healing rate in the aluminum phosphate group (25/42) versus 55% in the ranitidine group (27/49); this difference was not significant. Among the factors assessed, only one, the round shape of the ulcer, was significantly and independently associated with ulcer healing in a multidimensional analysis. In conclusion, this double-blind trial showed that aluminum phosphate is an effective, save and cheap treatment of acute duodenal ulcer.     

Comparative effectiveness of ranitidine (150 mg X 2) and cimetidine (400 mg x 2) in the treatment of acute duodenal ulcer. A French multicenter controlled clinical trial

In a single-blind multicenter trial, 444 patients with duodenal ulcer (DU) proven by endoscopy were randomly assigned to treatment with either ranitidine, 150 mg, or cimetidine, 400 mg, morning and evening. Clinical assessments were carried out at 2 and 4 weeks and endoscopy at 4 weeks. The patients in the 2 groups were comparable. Cumulative healing rates at 4 weeks were 78.3 p. 100 in the ranitidine group (n = 226) and 65.6 p. 100 in the cimetidine group (n = 218) (p less than 0.003). Pain at the start was of similar severity in both groups, and disappeared at the same rate under ranitidine or cimetidine: 64 p. 100 patients were painless at 1 week, 80 p. 100 at 2 weeks and 88 p. 100 at 4 weeks. Thirty-eight patients complained of mild side effects: 22 on ranitidine (2 trial withdrawals) and 16 on cimetidine (1 trial withdrawal). Multifactorial analysis (logistic model) revealed that linear ulcers had a lower healing probability than round ulcers (p less than 0.002) whatever the treatment group (cimetidine: 47 p. 100 vs 68 p. 100, ranitidine 57 p. 100 vs 80 p. 100 respectively). Smoking habits (p less than 0.057) and age less than 40 years (p = 0.056) did not significantly influence healing rates, although smokers and younger patients under cimetidine had the lowest healing rate. Thus, at the dosage used in our trial, ranitidine is more efficient for healing DU at 4 weeks than cimetidine but not for pain relief.(ABSTRACT TRUNCATED AT 250 WORDS)     

Double-blind controlled trial of cimetidine in the healing of gastric ulcer.

Sixty patients with gastric ulcers were treated for four weeks with either 1 g cimetidine per day or with identical tablets containing lactose. The healing rate, assessed by endoscopy, was 23 out of 35 (66%) in the patients given cimetidine and 13 out of 25 (52%) in those given placebo. The difference between the groups is not significant. During each of the four weeks of the study the cimetidine group experienced significantly fewer attacks of pain and consumed less antacids than the placebo treated patients.     

Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer.

In a double-blind randomised clinical trial a specific inhibition of peptic activity with a pentapeptide, pepstatin, had no significant advantage over placebo in the ulcer healing and symptomatology of duodenal ulcer. Thus, the inhibition of pepsin in human gastric juice does not appear to have a major influence on the healing of duodenal ulcer.     

Famotidine vs ranitidine h.s. in acute duodenal ulcer. A multicentre endoscopic trial.

A double-blind, randomized, active drug-controlled study was conducted in order to evaluate the efficacy and safety of famotidine vs ranitidine h.s. in promoting the healing of acute duodenal ulcers. Two hundred and eighty patients participated in the trial and received either famotidine 40mg h.s. or ranitidine, 300mg h.s. The two groups were not significantly different with regard to sex and risk factors such as alcohol consumption and family history of peptic ulcer disease, while in the famotidine group, there was a slightly higher number of patients who smoked. Endoscopy was performed at the end of 4 and 6 weeks in 248 patients (128 in the famotidine group and 120 in the ranitidine group). The healing rate in those receiving famotidine was 73.4% at the end of 4 weeks and increased to 93% at the end of 6 weeks, while in the ranitidine group, the rate was 75.8% and 92.5% respectively. Day and night pain markedly reduced in both groups and therapy was generally well tolerated.     

A pragmatic trial of cimetidine in duodenal ulcer patients.

Fifty-eight outpatients with a clinical and radiological diagnosis of duodenal ulcer completed a double-blind randomized trial of the effect of cimetidine on ulcer symptoms. Patients normally treated in general practice were included in the trial. The patients in the treatment group received cimetidine 1 g daily and the controls received inactive tablets. The treatment period was four weeks. During the last nine days 18 (60%) of 30 cimetidine-treated patients were symptom-free against 5 (18%) of 28 controls (P less than 0.005). The antacid consumption, the number of days with pain and the number of hours with pain also differed significantly in the two groups. Apart from a transient rash in one patient no important clinical side-effects were noted. The serum creatinine rose slightly in the cimetidine-treated patients.     

Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse. Double-blind comparative trial

In a double-blind, parallel-group clinical trial of 195 patients with duodenal ulcers who after a short-term study had relief of pain and healed ulcers proved endoscopically, 65 were randomized to receive 20 mg omeprazole 3 days a week (once in the morning from Friday to Sunday), 64 to receive 10 mg omeprazole once daily in the morning, and 66 to receive placebo for up to 6 months. The patients underwent repeat endoscopy with biopsy of the gastric fundic mucosa (qualitative assessment of argyrophilic cell population), assessment of symptoms, and laboratory screening with measurement of basal serum gastrin concentrations at 3 and 6 months or more often if indicated by recurrence of symptoms. At 3 months, endoscopically proved ulcer relapse occurred in 16% receiving 20 mg omeprazole 3 days a week; 21% receiving 10 mg omeprazole daily; and 50% receiving placebo. At 6 months, corresponding rates were 23%, 27%, and 67% with 95% confidence intervals of difference between the placebo group and omeprazole groups of 28%-60% and 24%-56% (P less than 0.00001), respectively, and between omeprazole groups of -19%-11% (NS). No major clinical or laboratory side effects were noted. Thus both omeprazole regimens are effective and safe in preventing duodenal ulcer relapse.     

A comparative study of once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating duodenal ulcers.

A randomized controlled study comparing once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating duodenal ulcers was carried out in 99 Japanese patients. Endoscopic examinations were performed at the baseline and repeated at 3-week intervals until healing was confirmed. Eighty-two patients fulfilled the evaluation criteria (38 in the morning group and 44 in the bedtime group). In 13 of these patients the antisecretory effects of these regimens were also assessed by 24 h intragastric pH monitoring. The healing rates were 66% after 3 weeks and 95% after 6 weeks in the morning group, and 57% after 3 weeks and 80% after 6 weeks in the bedtime group. The differences were insignificant between the two groups, but there was a higher healing rate tendency after 6 weeks in the morning group (0.05 less than P less than 0.10). Regarding pain subsidence, there were no significant differences between the two groups. Both treatments were significantly superior to the control group in increasing 24 h intragastric pH. The morning regimen was significantly superior to the bedtime regimen in suppression of daytime acidity. On the contrary, the bedtime regimen was significantly superior to the morning regimen in suppression of nocturnal acidity. These findings suggest that suppression of nocturnal acidity is important but not essential to promote duodenal ulcer healing and suppression of daytime acidity is equally important. Thus, once-a-day morning administration of 40 mg famotidine seems to be at least as effective as once-a-day bedtime administration of 40 mg famotidine in treating duodenal ulcers.     

Effects of cimetidine and poldine on nocturnal gastric secretion in duodenal ulcer.

Cimetidine inhibited nocturnal secretion of acid but only slightly inhibited the nocturnal secretion of pepsin in patients with duodenal ulcer. Administration of cimetidine (200 or 400 mg), together with an anticholinergic drug (poldine), augmented the inhibition of the nocturnal secretion of acid and of pepsin. The combination of an H2-receptor-blocking drug with an anticholinergic drug will have therapeutic application in the management of duodenal ulceration.     

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.     

Low-dose cimetidine in the acute treatment of duodenal ulcer. Comparison of a single nocturnal dose regimen with a twice daily regimen

A 0.5 g daily dose of cimetidine was as effective as a 1 g dose in the acute treatment of duodenal ulcer patients in Hong Kong. The aims of the present study were, first, to determine whether low-dose cimetidine treatment was as effective as standard doses in acute duodenal ulcer treatment of patients in Singapore, and second, to compare a single nocturnal dosage regimen with a twice daily regimen. In this single centre, double-blind, controlled trial, 282 patients with endoscopically proven duodenal ulcer were randomized to receive four weeks' treatment with cimetidine using one of three dosage regimens: (A) 800 mg at night; (B) 400 mg at night; or (C) 400 mg twice daily. Two hundred and forty-seven patients were evaluated. The incidences of healing at four weeks were: (A) 40/80 (50%), (B) 39/88 (44%); and (C) 48/79 (61%); (B vs C: P less than 0.05; A vs C: NS; 95% confidence limits: -5% to 27%; A vs B: NS, 95% confidence limits: -6% to 21%). Of 183 patients who had antral biopsies taken, 176 (96%) had histological gastritis, while 167 (91%) were positive for Helicobacter-like organisms. The occurrence of gastritis or Helicobacter-like organisms had no influence on ulcer healing. A 400 mg dose of cimetidine is therefore suboptimal for the treatment of duodenal ulcer in patients in Singapore. A single nocturnal dosage regimen may be less effective than a twice daily regimen.