Biomedical subjects

T J Simon

Publications and source records attributed to T J Simon.

At least 19 recordsLinked to original sources

PubMed2003

Famotidine for infant gastro-oesophageal reflux: a multi-centre, randomized, placebo-controlled, withdrawal trial.

BACKGROUND: Gastro-oesophageal reflux afflicts up to 7% of all infants. Histamine-2 receptor antagonists are the most commonly prescribed medications for this disorder, but few controlled studies support this practice. AIM: To evaluate the safety and efficacy of famotidine for infant gastro-oesophageal reflux disease. METHODS: Thirty-five infants, 1.3-10.5 months of age, entered an 8-week, multi-centre, randomized, placebo-controlled, two-phase trial: first 4 weeks, observer-blind comparison of famotidine 0.5 mg/kg and famotidine 1.0 mg/kg; second 4 weeks, double-blind withdrawal comparison (safety and efficacy) of each dose with placebo. RESULTS: No serious adverse events were reported. Eleven patients had 16 non-serious, possibly drug-related adverse experiences: 6 patients with agitation or irritability (manifested as head-rubbing in two), 3 patients with somnolence, 2 patients with anorexia, 2 with headache, 1 patient with vomiting, 1 patient with hiccups, and 1 patient with candidiasis. Of the 35 infants, 27 completed Part I. There were significant score improvements for famotidine 0.5 mg/kg in regurgitation frequency (P = 0.04), and for famotidine 1.0 mg/kg in crying time (P = 0.027) and regurgitation frequency (P = 0.004) and volume (P = 0.01). Eight infants completed Part II on double-blind treatment, which was insufficient for meaningful comparisons. CONCLUSIONS: Histamine-2 receptor antagonists may cause agitation and headache in infants. A possibly efficacious famotidine dose for infants is 0.5 mg/kg (frequency adjusted for age). As 1.0 mg/kg may be more efficacious in some, the dosage may require individualization based on response. Further sizeable placebo-controlled evaluations of histamine-2 receptor antagonists in infants with gastro-oesophageal reflux disease are warranted.

Administration, Oral↗

PubMed2001

Gastrointestinal medications and procedures in osteoarthritis patients treated with rofecoxib compared with nonselective NSAIDs.

CONTEXT: Patients treated with nonselective cyclooxygenase inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]) often experience dyspepsia and upper gastrointestinal (GI) adverse effects, and frequently require GI comedications and diagnostic procedures. OBJECTIVE: This study combined existing data to test the hypothesis that GI comedications and GI diagnostic procedures occur less frequently in osteoarthritis (OA) patients treated with rofecoxib compared with nonselective NSAIDs. DESIGN: Combined analysis of 8 randomized controlled clinical trials. SETTING: Rheumatology and general practice clinics. PATIENTS: Men and women aged 40 years and older with OA. INTERVENTIONS: Random assignment to placebo (n = 514), rofecoxib (n = 3357; 12.5, 25, or 50 mg daily combined; average 24.7 mg), or NSAIDs (n = 1564; ibuprofen 800 mg thrice daily, diclofenac 50 mg thrice daily, or nabumetone 1500 mg daily, combined). MAIN OUTCOME MEASURES: The cumulative incidence of patients using GI comedications (antacids, antispasmodics, antiflatulents, antiregurgitants, H2 antagonists, proton pump inhibitors, sucralfate, prostaglandins, other antiulcer therapy) and needing GI procedures (upper GI barium studies, upper or lower GI endoscopies) over 12 months. RESULTS: Compared with those treated with NSAIDs, patients treated with rofecoxib had a significantly lower incidence of GI comedication use (17.5% vs 27.0%, P <.001) and GI procedures (3.3% vs 5.3%, P =.02) over 12 months. Similar results were seen in analyses of protocols with placebo; in these studies, rates of GI comedications and procedures were highest with NSAIDs, while those with rofecoxib and placebo were similar to each other. CONCLUSIONS: OA patients treated with rofecoxib for up to 12 months required significantly less GI comedication and significantly fewer GI procedures than those treated with NSAIDs.

Adult↗

PubMed2001

Review article: the gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase-2, in humans.

Highly selective inhibitors of cyclooxygenase-2, such as rofecoxib, are hypothesized to have an improved gastrointestinal tolerability and safety profile compared with non-selective NSAIDs, which inhibit cyclooxygenase-1 and cyclooxygenase-2 non-selectively. This paper reviews data from randomized, double-blind, placebo-controlled studies which investigated the effects of rofecoxib and NSAIDs on the human gastrointestinal tract. In healthy subjects, rofecoxib 25 mg and 50 mg daily had no effect on gastric mucosal prostaglandin synthesis, whilst naproxen 1000 mg daily caused a 70% reduction. Therapeutic doses of rofecoxib 25 mg and 50 mg daily did not increase intestinal permeability or faecal blood loss in healthy subjects, whereas increases in both measures were seen with indometacin 150 mg or ibuprofen 2400 mg. A supra-therapeutic dose of rofecoxib (250 mg) given daily for 7 days did not induce an increase in gastroduodenal erosions in healthy subjects, whilst increased numbers of erosions were found in subjects given ibuprofen 2400 mg or aspirin 2600 mg. The endoscopic findings in healthy subjects were confirmed in two 6-month clinical studies involving 1516 patients with osteoarthritis; the incidences of ulcers following rofecoxib 25 mg or 50 mg daily were similar to placebo and less than ibuprofen 2400 mg. The advantage of rofecoxib over NSAIDs in these studies appears to translate into clinically relevant benefits; an analysis of 5435 patients with osteoarthritis found a significantly lower incidence of gastrointestinal perforations, ulcers and bleeds in patients taking rofecoxib compared with patients taking NSAIDs. Overall, the findings from these studies suggest that, as a result of cyclooxygenase-1 sparing, rofecoxib is significantly less gastrotoxic than non-selective NSAIDs, and may not differ from placebo.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Gastrointestinal tolerability of the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib compared with nonselective COX-1 and COX-2 inhibitors in osteoarthritis.

BACKGROUND: Most nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective cyclooxygenase (COX-1 and COX-2) inhibitors and are associated with a variety of upper gastrointestinal (GI) tract symptoms. The roles of COX-1 and COX-2 in the pathogenesis of these symptoms are unclear. To test whether COX-2 inhibition with rofecoxib would have greater GI tolerability than nonselective COX-1 and COX-2 inhibition, we compared the incidences of (1) treatment discontinuations for GI adverse events (AEs) and (2) prespecified dyspeptic-type GI AEs among patients with osteoarthritis treated with rofecoxib vs NSAIDs. METHODS: A prespecified, combined analysis of investigator-reported GI AEs in all 8 double-blind, randomized, phase 2b/3 osteoarthritis trials of rofecoxib was conducted. Patients included men and women with osteoarthritis (N = 5435); there was no upper age limit for entry. Treatments tested included rofecoxib, 12.5, 25, or 50 mg (combined), vs ibuprofen, diclofenac, or nabumetone (combined). Primary outcomes were the time (by survival analysis) to (1) treatment discontinuation due to GI AEs and (2) first reported dyspeptic-type GI AE. Between-treatment comparisons were made by log-rank test. RESULTS: The number of treatment discontinuations caused by GI AEs during 12 months was significantly lower (P=.02) with rofecoxib vs NSAIDs (8.2 vs 12.0 per 100 patient-years; relative risk, 0.70; 95% confidence interval, 0.52-0.94). The incidence of prespecified dyspeptic-type GI AEs during the first 6 months was significantly lower (P=.02) with rofecoxib vs NSAIDs (69.3 vs 85.2 per 100 patient-years; relative risk, 0.85; 95% confidence interval, 0.74-0.97). However, the difference between treatments in dyspeptic-type GI AEs was attenuated after 6 months. CONCLUSION: Rofecoxib was associated with a lower incidence of treatment discontinuations due to GI AEs over 12 months and a lower incidence of dyspeptic-type GI AEs over 6 months than treatment with nonselective COX inhibitors, or NSAIDs. Arch Intern Med. 2000;160:2998-3003

Abdominal Pain↗

PubMed2000

A randomized trial measuring fecal blood loss after treatment with rofecoxib, ibuprofen, or placebo in healthy subjects.

PURPOSE: Gastrointestinal microbleeding, as assessed by the measurement of (51)chromium-labeled red blood cells, is a marker of the mucosal injury associated with the use of nonsteroidal anti-inflammatory drugs. This study tested the hypotheses that cyclooxygenase-2 specific inhibition with rofecoxib would cause less fecal blood loss than a therapeutic dose of ibuprofen and would be equivalent to placebo. SUBJECTS AND METHODS: In this randomized, double-blind group study, gastrointestinal blood loss was assessed by measurement of fecal (51)chromium radioactivity during a 1-week placebo baseline period and during 4 weeks of treatment with rofecoxib (25 mg or 50 mg once daily), ibuprofen (800 mg three times daily), or placebo in 67 healthy subjects. Gastrointestinal blood loss during treatment weeks 2 to 4 (versus the baseline period) was expressed as the geometric mean ratio of fecal radioactivity in weeks 2 to 4 compared with baseline. RESULTS: Ibuprofen caused significantly (P <0.001) greater gastrointestinal blood loss (geometric mean ratio of 5.2, 95% confidence interval [CI]: 4.2 to 6.3) than the 25-mg dose of rofecoxib (2.6, 95% CI: 2.2 to 3.1), the 50-mg dose of rofecoxib (2.6, 95% CI: 2.2 to 3.0), or placebo (2.1, 95% CI: 1.8 to 2.5). In contrast, gastrointestinal blood loss with both doses of rofecoxib were equivalent to placebo by a predetermined clinical similarity bound. CONCLUSIONS: In healthy subjects, treatment with rofecoxib, at 2 to 4 times the doses that are currently recommended for the treatment of patients with osteoarthritis, produced significantly less fecal blood loss than a therapeutic dose of ibuprofen and was equivalent to placebo.

Adult↗

PubMed1999

Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs.

CONTEXT: Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) toxic effects, such as upper GI tract perforations, symptomatic gastroduodenal ulcers, and upper GI tract bleeding (PUBs), are thought to be attributable to cyclooxygenase 1 (COX-1) inhibition. Rofecoxib specifically inhibits COX-2 and has demonstrated a low potential for causing upper GI injury. OBJECTIVE: To compare the incidence of PUBs in patients with osteoarthritis treated with rofecoxib vs NSAIDs. DESIGN: Prespecified analysis of all 8 double-blind, randomized phase 2b/3 rofecoxib osteoarthritis trials conducted from December 1996 through March 1998, including one 6-week dose-ranging study, two 6-week efficacy studies vs ibuprofen and placebo, two 1-year efficacy studies vs diclofenac, two 6-month endoscopy studies vs ibuprofen and placebo, and one 6-week efficacy study vs nabumetone and placebo. SETTING: Multinational sites. Participants Osteoarthritis patients (N = 5435; mean age, 63 years [range, 38-94 years]; 72.9% women). INTERVENTIONS: Rofecoxib, 12.5, 25, or 50 mg/d (n = 1209, 1603, and 545, respectively, combined) vs ibuprofen, 800 mg 3 times per day (n = 847), diclofenac, 50 mg 3 times per day (n = 590); or nabumetone, 1500 mg/d (n = 127) (combined). MAIN OUTCOME MEASURE: Cumulative incidence of PUBs for rofecoxib vs NSAIDs, based on survival analysis of time to first PUB diagnosis, using PUBs that met pre-specified criteria judged by a blinded, external adjudication committee. RESULTS: The incidence of PUBs over 12 months was significantly lower with rofecoxib vs NSAIDs (12-month cumulative incidence, 1.3% vs 1.8%; P = .046; rate per 100 patient-years, 1.33 vs 2.60; relative risk, 0.51; 95% confidence interval, 0.26-1.00). The cumulative incidence of dyspeptic GI adverse experiences was also lower with rofecoxib vs NSAIDS over 6 months (23.5% vs 25.5%; P = .02), after which the incidence rates converged. CONCLUSION: In a combined analysis of 8 trials of patients with osteoarthritis, treatment with rofecoxib was associated with a significantly lower incidence of PUBs than treatment with NSAIDs.

Adult↗

PubMed1999

Specific inhibition of cyclooxygenase-2 with MK-0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen.

BACKGROUND: Compared with currently available NSAIDs (which inhibit COX-1 and COX-2 isoforms of cyclooxygenase), MK-0966 (a specific COX-2 inhibitor) is expected to cause less gastrointestinal toxicity. AIM: To compare the effect on the upper gastrointestinal mucosae of a high dose of MK-0966 with that of conventional doses of ibuprofen and aspirin. METHODS: Healthy subjects (n = 170; age range 18-54 years) with endoscopically normal gastric and duodenal mucosa were randomized to either MK-0966 250 mg q.d. (n = 51), ibuprofen 800 mg t.d.s. (n = 51), aspirin 650 mg q.d.s. (n = 17), or placebo (n = 51) in this 7-day, double-blind, parallel-group study. The mucosae were evaluated by endoscopy using a predefined scale; scores could range from 0 to 4. The primary end-point was the percentage of subjects who developed a mucosal score >/= 2 (i.e. the development of one or more erosions). To evaluate COX-1 activity, serum thromboxane B2 levels were determined in a subset of the population. RESULTS: The percentage of subjects who developed a mucosal score >/= 2 in the MK-0966 group (12%) was significantly lower (P < 0.001) than that in the ibuprofen (71%) and aspirin (94%) groups, and was similar to that in the placebo group (8%). Only ibuprofen and aspirin significantly (P < 0.0001) reduced baseline thromboxane B2 levels. All treatments were generally well tolerated. CONCLUSIONS: In this acute short-term endoscopic study, MK-0966 250 mg q.d. (a dose at least 10 times higher than that demonstrated to reduce the signs and symptoms of osteoarthritis) produced significantly less gastrointestinal mucosal damage than either ibuprofen 800 mg t.d.s. or aspirin 650 mg q.d.s. and was comparable to placebo in this regard.

Adolescent↗

PubMed1999

Neural evidence linking visual object enumeration and attention.

Visual object enumeration is rapid and accurate for four or fewer items but slow and error-prone for over four items. This dichotomy has recently been linked to visual attentional phenomena by findings suggesting that 'subitizing' of small sets of objects is preattentive whereas 'counting' of over four items demands spatial shifts of attention. We evaluated this link at a neural level, using H2 15-O positron emission tomography to measure changes in regional cerebral blood flow while subjects enumerated the number of target vertical bars that 'popped out' of a 16-bar visual display consisting of both horizontal and vertical bars. Relative to a condition with a single target, subitizing (one to four targets) activated foci in the occipital extrastriate cortex, consistent with involvement of early, preattentive visual processes. Relative to subitizing, counting (five to eight targets) activated a widespread network of brain regions, including multiple foci implicated in shifting visual attention-large regions of the superior parietal cortex bilaterally and a focus in the right inferior frontal cortex. These results offer the first direct neural support for mapping the subitizing-counting dichotomy onto separable processes mediating preattentive vision and shifts of visual attention.

Adolescent↗

PubMed1998

Effects of alendronate on gastric and duodenal mucosa.

OBJECTIVES: This single-center, double-blind, randomized study assessed the effect of alendronate 5 and 10 mg on the gastroduodenal mucosa. METHODS: Overall, 95 postmenopausal women without a recent history of major upper gastrointestinal (GI) disease and not taking gastric-irritant drugs, were screened with an upper GI endoscopy. Fourteen women (15% of the total) were found to have baseline endoscopic gastric and/or duodenal abnormalities, including mucosal hemorrhages (n = 4), erosions (n = 11), and ulcers (n = 3). Two additional women had baseline esophageal abnormalities. Thus, 79 postmenopausal women (mean age 51 yr, range 41-64 yr), free of esophageal, gastric and/or duodenal erosions or ulcer, were enrolled. Subjects received placebo, alendronate 5 mg/day or 10 mg/day, or aspirin 650 mg q.i.d. for 14 days. Endoscopy was repeated on Day 8 and on Day 15. Gastric and duodenal mucosae were graded separately using a 5-point scale for erosive mucosal injury. RESULTS: The proportions of subjects with a gastric or duodenal erosion score > or = 2 (presence of at least one mucosal erosion) on either Day 8 or 15 were four of 22 (18.2%) in the placebo group; four of 22 (18.2%) in the alendronate 5 mg group; five of 21 (23.8%) in the alendronate 10 mg group; and 14 of 14 (100.0%) in the aspirin group. Thirty-five of 76 (46%) subjects were H. pylori-positive (Pyloritek test), and were equally distributed across treatment groups. CONCLUSIONS: Alendronate 5 and 10 mg/day for 2 wk was associated with a lower incidence of gastric erosions than aspirin. The incidence of gastric erosions in the alendronate groups did not differ significantly from the placebo group. In this study, unlike aspirin, alendronate did not induce gastric erosions.

Adult↗

PubMed1998

Do the magnocellular and parvocellular visual pathways contribute differentially to subitizing and counting?

We investigated the neurobiological basis of visual processes involved in object enumeration. Subitizing, the ability to rapidly and accurately enumerate four or fewer objects, is thought to depend on preattentive processing of visual stimuli, whereas counting of more numerous objects is thought to require serial shifts of attention. We attempted to distinguish between the hypothesis that the magnocellular (M) visual pathway is the preferential route for subitizing, and the alternative hypothesis that there is no selectivity for the M pathway or its counterpart, the parvocellular (P) visual pathway, in visual object enumeration. Green rectangles were presented on an equiluminant red background to impair M pathway processing. This slowed enumeration performance relative to a control condition in which object/background luminance differed, especially when the rectangles were relatively large and widely spaced and had constant retinal eccentricity. When low luminance contrast was used to impair processing along the P pathway, enumeration performance was slowed relative to a high-contrast control condition, especially when the rectangles were small and closely spaced. Overall, our manipulations affected enumeration performance without selectivity for subitizing or counting ranges and without altering the slope of the functions relating reaction time to numerosity. Thus, our results favor the hypothesis that visual enumeration does not depend preferentially on either the M or the P pathway.

Humans↗

PubMed1997

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study.

INTRODUCTION: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing. AIM: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole. PATIENTS AND METHODS: Patients whose active erosive reflux oesophagitis (grade > or = 2) had healed (grade 0 or 1) after 4-8 weeks of open-label omeprazole 40 mg daily (phase I) were eligible to join a multi-centre, 6-month double-blind, placebo-controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n = 138), 20 mg omeprazole for 3 consecutive days each week (n = 137), or placebo (n = 131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse. RESULTS: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P < 0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3-days-a-week (P < 0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells. CONCLUSIONS: These results show that after healing of erosive oesophagitis with 4-8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.

Anti-Ulcer Agents↗

PubMed1997

Leukotrienes in ulcerative colitis: results of a multicenter trial of a leukotriene biosynthesis inhibitor, MK-591.

BACKGROUND & AIMS: Leukotrienes (LTs) are believed to be important in the pathogenesis of ulcerative colitis (UC). The aim of this study was to determine whether inhibition of LT biosynthesis with a 5-lipoxygenase inhibitor (MK-591) induces remission in patients with mild to moderate UC. METHODS: One hundred eighty-three patients with mild to moderately active UC enrolled in this randomized parallel group, double-blind study. Patients received placebo or MK-591 at a dose of 12.5, 50, or 100 mg twice daily for 8 weeks. A subset of patients underwent rectal dialysis to determine LTB4 concentration. RESULTS: MK-591 reduced LTB4 concentrations in rectal dialysate at the final determination. The median percent of baseline LTB4 concentration for 100 mg taken twice daily was 1.4% (n = 4); for 50 mg taken twice daily, 16.5% (n = 6); for 12.5 mg taken twice daily, 12% (n = 6); and for placebo, 78% (n = 6). There was no correlation between reduction of LTB4 and remission. Patients in remission at week 8 were as follows: placebo, 9 of 44 (20.5%); 100 mg taken twice daily, 11 of 43 (25.6%); 50 mg taken twice daily, 8 of 49 (16.3%); and 12.5 mg taken twice daily, 4 of 47 (8.5%) (P > 0.10). CONCLUSIONS: MK-591 markedly inhibited LT biosynthesis, but it did not differ significantly from placebo in clinical efficacy. Inhibition of LT biosynthesis was not effective as a single therapeutic modality in active UC.

Adolescent↗

PubMed1996

Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs.

BACKGROUND: Acid suppression with famotidine, a histamine H2-receptor antagonist, provides protection against gastric injury in normal subjects receiving short courses of aspirin or naproxen. The efficacy of famotidine in preventing peptic ulcers in patients receiving long-term therapy with nonsteroidal antiinflammatory drugs (NSAIDs) is not known. METHODS: We studied the efficacy of two doses of famotidine (20 mg and 40 mg, each given orally twice daily), as compared with placebo, in preventing peptic ulcers in 285 patients without peptic ulcers who were receiving long-term NSAID therapy for rheumatoid arthritis (82 percent) or osteoarthritis (18 percent). The patients were evaluated clinically and by endoscopy at base line and after 4, 12, and 24 weeks of treatment. The evaluators were unaware of the treatment assignment. The primary end point was the cumulative incidence of gastric or duodenal ulceration at 24 weeks. RESULTS: The cumulative incidence of gastric ulcers was 20 percent in the placebo group, 13 percent in the group of patients receiving 20 mg of famotidine twice daily (P = 0.24 for the comparison with placebo), and 8 percent in the group receiving 40 mg of famotidine twice daily (P = 0.03 for the comparison with placebo). The proportion of patients in whom duodenal ulcers developed was significantly lower with both doses of famotidine than with placebo (13 percent in the placebo group, 4 percent in the low-dose famotidine group [P = 0.04], and 2 percent in the high-dose famotidine group [P = 0.01]). Both doses of famotidine were well tolerated. CONCLUSIONS: Treatment with high-dose famotidine significantly reduces the cumulative incidence of both gastric and duodenal ulcers in patients with arthritis receiving long-term NSAID therapy.

Adult↗

PubMed1996

Subitizing and counting depend on different attentional mechanisms: evidence from visual enumeration in afterimages.

Two experiments showed that, when selective eye movements were disabled by the presentation of stimuli in the form of afterimages, increased inspection time and facilitative stimulus configurations failed to increase the subitizing limit of 4 objects. Afterimages of two to eight dots induced by a photographic flashgun were shown to 3 adult subjects. For more than 4 objects, enumeration errors occurred at a rate of 20%-30%. Enumeration was effectively perfect for 2-4 linearly configured dots, with occasional errors surprisingly occurring in that range when dots appeared in groups of up to 3 items. No errors occurred in nonafterimage control conditions. Enumeration errors were attributed to failures of individuating dots to be counted due to the deactivation of selective eye movements in afterimages. A third experiment supported this interpretation by disabling eye movements with briefly presented stimuli and producing results much like those of the afterimage conditions.

Adult↗

PubMed1996

Comparison of once-daily doses of omeprazole (40 and 20 mg) and placebo in the treatment of benign gastric ulcer: a multicenter, randomized, double-blind study.

OBJECTIVE: The purpose of this multicenter, randomized, double-blind study, conducted in 520 patients, was to compare the efficacy and safety of omeprazole (40 and 20 mg once daily) with placebo in the treatment of benign gastric ulcer. METHODS: Treatment with omeprazole or placebo lasted 4 wk; those whose ulcers remained unhealed continued the same treatment regimen for an additional 4 wk. The effects of therapy were determined by endoscopy and assessment of GI symptoms. Safety and tolerability were evaluated through reported adverse events, physical examinations, and laboratory tests. RESULTS: At weeks 4 and 8, the proportion of patients with healed ulcers was significantly greater in the omeprazole 40- and 20-mg groups than in the placebo group (p < 0.01). At week 8, the healing rate was significantly greater in the 40-mg group than in the 20-mg group (82.7 vs 74.8%, p < 0.05). In patients with large ulcers (>1 cm), the 40-mg regimen was associated with a significantly higher healing rate (78.9%) than both the 20-mg regimen (61.4%) and placebo (34.6%) at week 8 (p < 0.05 vs omeprazole 20 mg; p < 0.01 vs placebo). Healing rates in patients with small ulcers were similar for the 40- and 20-mg groups. Omeprazole was well tolerated, with no significant differences versus placebo in the overall incidence of clinical or laboratory adverse events. CONCLUSIONS: Omeprazole 40 and 20 mg, administered once daily, healed a significantly greater proportion of patients than did placebo. The 40-mg regimen offered significant advantages over the 20-mg regimen in patients with large ulcers.

Double-Blind Method↗

PubMed1994

Randomized, placebo-controlled comparison of famotidine 20 mg b.d. or 40 mg b.d. in patients with erosive oesophagitis.

METHODS: This US multicentre, randomized, double-blind, placebo-controlled, parallel group study determined the effects of two twice daily oral famotidine regimens on symptom relief and healing of erosive oesophagitis in patients with gastro-oesophageal reflux disease. Three hundred and eighteen patients were enrolled: 66 received placebo, 125 received famotidine 20 mg b.d., and 127 received famotidine 40 mg b.d. Patients maintained diaries of their symptoms. Endoscopy was performed at weeks 0 and 6, and again at week 12 if healing had not occurred. RESULTS: Healing at 6 and 12 weeks was (respectively) 48% (P < or = 0.01 vs. placebo) and 69% (P < or = 0.01 vs. placebo) for famotidine 40 mg b.d.; 32% and 54% (P < or = 0.01 vs. placebo) for famotidine 20 mg b.d., and 18% and 29% for placebo. At both 6 and 12 weeks the healing rates of famotidine 40 mg b.d. were significantly greater than placebo and famotidine 20 mg b.d. Compared to placebo, famotidine produced more frequent global symptom improvement and more rapid heartburn relief. There were no significant differences among treatment groups in the incidence of clinical or laboratory adverse events. CONCLUSIONS: Famotidine 40 mg b.d. was a better regimen than famotidine 20 mg b.d. or placebo. The clinical efficacy paralleled the previously documented effect of the famotidine regimens on decrease of oesophageal acid exposure.

Administration, Oral↗

PubMed1993

Efficacy of twice daily doses of 40 or 20 milligrams famotidine or 150 milligrams ranitidine for treatment of patients with moderate to severe erosive esophagitis. Famotidine Erosive Esophagitis Study Group.

The comparative efficacy of twice daily regimens of 40 mg famotidine (group 1), 20 mg famotidine (group 2), and 150 mg ranitidine (group 3) was investigated in a double-blind randomized study of parallel groups of patients with endoscopically documented erosive esophagitis. Patients were enrolled at 29 centers in 19 countries and treated for 6 to 12 weeks until healing, defined as complete resolution of visible ulceration or erosion of the esophageal mucosa, demonstrated by repeat endoscopy. Healing occurred in 71% of 175 group-1 patients, 68% of 93 group-2 patients, and 60% of 172 group-3 patients; the difference between groups 1 and 3 was significant (P < or = 0.05). The three treatments produced similar levels of global symptomatic improvement and relief of daytime and nighttime heartburn. All treatments were well tolerated. These results support the hypothesis that reduction of esophageal acid exposure by 40 mg famotidine twice daily produces healing of lesions in patients with erosive esophagitis and is more effective than regimens that provide lesser reductions in esophageal acid exposure time.

Double-Blind Method↗

PubMed1991

Comparative tolerability profile of omeprazole in clinical trials.

The tolerability of omeprazole was compared to control agents in 68 clinical studies that enrolled a total of 4846 patients, of whom 3096 received omeprazole. The incidence of adverse experiences was independent of omeprazole dose administered, the age of the patients, and the disease treated (duodenal ulcer or endoscopically verified gastroesophageal reflux disease). The most common clinical adverse experiences were headache, diarrhea, abdominal pain, and nausea. The most common laboratory adverse experiences were elevated aspartate aminotransferase and elevated alanine aminotransferase. Omeprazole was well tolerated, and the incidence of clinical and laboratory adverse experiences was similar in patients receiving omeprazole, placebo, cimetidine, or ranitidine.

Adolescent↗