Roxatidine in duodenal ulcer.CM Habibullah, MA Habeeb, SP Singh
Dept of Gastroenterology, Osmania Medical College, Osmania General Hospital, Hyderabad.
Roxatidine acetate is a new H2-receptor antagonist. A randomized double-blind clinical trial in fifty-three patients with endoscopically proven duodenal ulcers > 5 mm in diameter was undertaken to compare safety and efficacy of roxatidine with that of ranitidine. Twenty-six patients received roxatidine (75 mg bid) while 27 patients received ranitidine (150 mg bid) for 4 weeks. One patient in each group did not come for follow up. Roxatidine and ranitidine had comparable ulcer healing rates (22/25 vs 22/26); roxatidine, however, resulted in greater reduction in the number and severity of night time pain episodes (p < 0.05). No adverse event was reported during 4 weeks of treatment with roxatidine. Thus roxatidine achieves the primary therapeutic goal of relief of pain better than ranitidine.
Keywords: Adult, Comparative Study, Double-Blind Method, Drug Administration Schedule, Duodenal Ulcer, diagnosis,drug therapy,Female, Follow-Up Studies, Histamine H2 Antagonists, administration &dosage,Human, Male, Pain Measurement, Piperidines, administration &dosage,Ranitidine, administration &dosage,Treatment Outcome,
H2-receptor antagonists are now the most widely used therapeutic agents in the treatment of peptic ulcers. The main stay of therapy for peptic ulcers is inhibition of gastric acid secretion. This requisite has to be fulfilled effectively by all H2- receptor antagonists. However, one of the primary therapeutic goals in such patients is relief of pain and it is in this aspect that further improvement is possible in the therapeutic efficacy of newer H2-receptor antagonists.
Roxatidine acetate is a new H2-receptor antagonist with a novel chemical structure. It is a piperidine derivative unlike cimetidine, ranitidine and famotidine, which are imidazole, furan and thiazole derivatives, respectively. It is well tolerated in healthy volunteers in single as well as multiple doses. It effectively inhibits both day-time and night-time secretion of gastric acid and has been shown to be twice as potent as ranitidine in inhibiting gastric acid production.
The present study was undertaken to compare the safety and efficacy of roxatidine acetate with that of ranitidine in duodenal ulcers in an Indian population.
The study was a randomised, double-blind trial (using a double dummy technique) comparing roxatidine (75 mg bid) with ranitidine (150 mg bid) given for 4 weeks. The Ethics Committee of the hospital approved the study protocol. Patients with endoscopically confirmed uncomplicated duodenal ulcers, either solitary or multiple with a minimum diameter of 5 mm. were enrolled in the study. A detailed clinical history was taken and thorough examination undertaken.
Pregnant women, lactating mothers patients having Zollinger-Ellison syndrome malignancy or complications of duodenal ulcer viz bleeding stricture obstruction and perforation and those with evidence or renal, hepatic, cardiac, respiratory, hematological or bleeding disorders were excluded from the study. Informed written consent was obtained from each patient. Endoscopy was done within 3 days of enrolment into the study and at the end of 4 weeks. The site, size and number of ulcers were recorded. Ulcer healing on endoscopy was assessed as complete healing, improvement unchanged or aggravated.
Pain relief was assessed in 2 ways: a) daily diary: patients were instructed to keep a daily record of number and severity of day and night-time pain episodes; and b) Weekly follow-up visits: patients were asked whether pain relief was 25%, 50%, 75% or 100% as compared to the previous visit.
All patients were subjected to laboratory investigations (leucocyte count, ESR. Serum bilirubin, Serum Creatinine, BUN, Fasting blood sugar. SGOT, SGPT and routine urinalysis), before and after treatment. A careful watch was kept for any adverse event at every follow up visit.
Statistical Analysis: The statistical tests used for inter-group comparisons were the test, Wilcoxon's rank sum test, Fisher's exact probability test and analysis of covariance.
Fifty-three patients with duodenal ulcer were randomised to the roxatidine group (24 men, 2 women; aged 38.0 + 3.0 yr) and the ranitidine group (24 men, 3 women aged 38.0 + 2.7 yr). Both groups had long standing ulcers, ranging from 1-5 yr. There was no significant difference in the demographic data, clinical profile or patients in the two treatment groups. All 53 patients had solitary duodenal ulcers, the mean size being 8.6 mm and 9.8 mm in the roxatidine and ranitidine groups respectively. One patient each in the two groups failed to report for follow-up: these patients were excluded from the analysis.
Pain relief, assessed at weekly follow up, was similar in the two treatment groups. Data collected through the self-assessment diaries were analysed for the number of episodes and severity of day-time and night-time pain [Table - 1]. The decline in the number and severity score of day-time pain episodes was comparable in the two groups, at the end of 4 weeks. However the roxatidine group showed higher percentage reduction in the number (93.8% vs 75.3%; p < 0.05) and severity scores (97.1 % vs 85.5%; p < 0. 05) of night-time pain episodes. The reduction in pain from the baseline values was tested by analysis of covariance with baseline values as covariates.
At 4 weeks, endoscopy showed complete ulcer 6. healing in 22125 (88%) patients on roxatidine and 22/26 (84.6%) patients on ranitidine (p = ns). Three patients in each group had partial healing. One patient failed to respond to ranitidine while none in the roxatidine group showed any failure of healing. None of the patients in either group had adverse event.
Our study shows that roxatidine 75 mg twice a day and ranitidine 150 mg twice a day for 4 weeks resulted in comparable duodenal ulcer healing. However, patients on roxatidine showed a significantly greater reduction in the number and severity of night-time pain episodes, as compared to ranitidine.
Our findings are similar to those of several other clinical trials from Europe, Japan and USA which show that roxatidine is comparable to other H2 receptor antagonists in terms of cumulative healing rates, The superior night-time pain relief that we observed with roxatidine is particularly important from the patient's point of view.
The present study also shows that roxatidine is well-tolerated by Indian patients, with no patient reporting any adverse event during 4 weeks of treatment.
We thank the Superintendent, Osmania General Hospital for allowing us to carry out the study and Hoechst India Limited for providing the study material and medications for the trial.
[Table - 1]