A double-blind study of pantoprazole and omeprazole in the treatment of reflux oesophagitis : a multicentre trial

Background: Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H⁺,K⁺-ATPase. Aim:To compare pantoprazole 40 mg with omeprazol 20 mg as once daily dosing in the treatment of reflux oesophagitis (grades II and III). Methods: This double-blind, randomized, multicentre study included 286 patients. Patients were reendoscoped after 4 weeks, and continued to receive a further 4 weeks of treatment if they were not healed a this time. Results: After 4 weeks of treatment, complete healing occurred in 126/170 (74%) patients in the pantoprazole group and in 67/86 (78%) patients in the omeprazole group (per-protocol analysis). At 8 weeks, the corresponding healing rates were 153/170 (90%) and 81/86 (94%). The differences between the treatment groups were not significant (P= 0.57 and 0.34). Improvement in the principal symptoms of reflux oesophagitis was also very similar between the treatment groups, with 59% and 69% at 2 weeks, and 83% and 86% at 4 weeks, respectively, being free from any individual symptom. Both treatments were well tolerated. Conclusions: This study has shown pantoprazole and omeprazole to be similarly effective and well tolerated in the treatment of mild to moderate reflux oesophagitis.     

Comparable clinical efficacy and tolerability of 20 mg pantoprazole and 20 mg omeprazole in patients with grade I reflux oesophagitis

BACKGROUND: Several clinical trials have shown that pantoprazole (40 mg) and omeprazole (40 or 20 mg) have similar efficacy and safety in the treatment of grade II-IV reflux oesophagitis (Savary-Miller classification). AIM: To compare the efficacy and safety of once-daily doses of pantoprazole (20 mg) and omeprazole (20 mg) with respect to symptom relief and healing of patients with grade I reflux oesophagitis. METHODS: Patients with endoscopically established grade I reflux oesophagitis (non-confluent, patchy red lesions with/without white fibrin coating) were enrolled into this randomized, open, parallel-group, multicentre study. A total of 328 patients (n=166 in the pantoprazole group, n=162 in the omeprazole group) were recruited in 23 centres. Patients received 4 weeks of treatment. If the reflux oesophagitis was not completely healed, the treatment was extended to 8 weeks. RESULTS: After 2 and 4 weeks of treatment with either pantoprazole or omeprazole, the rate of symptom relief was similar (70% vs. 79% and 77% vs. 84%, respectively). High healing rates were observed after 4 and 8 weeks (pantoprazole: 84% and 90%, respectively; omeprazole: 89% and 95%, respectively). Both treatments were well tolerated. The most frequently reported adverse events on pantoprazole and omeprazole, respectively, were nausea (8% vs. 7%), diarrhoea (5% vs. 6%) and headache (6% vs. 3%). CONCLUSIONS: After 4 and 8 weeks of treatment with pantoprazole (20 mg) or omeprazole (20 mg), patients with mild gastro-oesophageal reflux disease (grade I) showed comparably high rates of symptom relief and healing. Both treatments were safe and well tolerated.     

Efficacy and tolerability of pantoprazole 40 mg versus 80 mg in patients with reflux oesophagitis.

BACKGROUND: Pantoprazole is a substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+, K+- ATPase. METHODS: Pantoprazole 40 mg and 80 mg were compared in a randomized double-blind study in 192 out-patients with stage II or III (Savary-Miller classification) reflux oesophagitis. Patients received either pantoprazole 40 mg (n = 97) or pantoprazole 80 mg (n = 95), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the oesophagitis had not healed. RESULTS: After 4 weeks complete healing of the reflux oesophagitis was seen in 78% of protocol-correct patients given pantoprazole 40 mg daily (n = 86), and in 72% in the 80 mg (n = 87) group. The cumulative healing rates after 8 weeks were 95 and 94%, respectively (P > 0.05, Cochran-Mantel- Haenszel), and time until healing of oesophagitis comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse event or changes in laboratory values of clinical significance could definitely be ascribed to the trial medication. CONCLUSION: The 40 mg pantoprazole dosage is comparable to 80 mg in reflux oesophagitis, both in efficacy and tolerability.     

Pantoprazole versus omeprazole in the treatment of acute gastric ulcers

Background: Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H⁺,K⁺-ATPase. Methods: The proton pump inhibitors pantoprazole and omeprazole were compared in a randomized, doubleblind study in 219 patients with benign gastric ulcers. Patients received either pantoprazole 40 mg (n= 146) or omeprazole 20 mg (n= 73), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the ulcer had not healed. Results: After 4 weeks, complete ulcer healing was seen in 88% of protocol-correct patients given pantoprazole and in 77% given omeprazole (between-group difference P < 0.05). At 8 weeks, the corresponding values were 97% and 96% (not significant). In the comparative intention-to-treat analysis there were no statistical differences between the treatment groups. Among the patients who had ulcer pain prior to treatment, 79% of the pantoprazole group and 68% of the omeprazole group were pain-free after 2 weeks, and after 4 weeks 88% and 81%, respectively (not significant). Pronounced improvement in the other gastrointestinal symptoms was seen in both groups. Only 10% of patients in each group reported adverse events. There were moderate increases in fasting serum gastrin levels with both treatments at 4 and 8 weeks. Conclusion: Pantoprazole, 40 mg once daily in the morning, is a highly effective, well tolerated treatment for acute, benign gastric ulcer. Pantoprazole and omeprazole were equally safe in the therapy of gastric ulcer.     

Comparison of pantoprazole versus omeprazole in the treatment of acute duodenal ulceration—a multicentre study

Methods: In this randomized, double-blind, multicentre study, the proton pump inhibitors pantoprazole and omeprazole were compared in patients with active duodenal ulcers. Two hundred and seventy-six protocol-correct patients received either pantoprazole 40 mg (n= 185) or omeprazole 20 mg (n= 91), once daily for 2 or 4 weeks, depending on the progress of ulcer healing. Results: Rates of complete ulcer healing after 2 weeks were 71% in patients given pantoprazole and 74% in patients given omeprazole. After 4 weeks the figures were 96% and 91%, respectively. These differences were not significant. There was no significant difference in ulcer pain prior to treatment, and 85% of the pantoprazole group and 86% on omeprazole were pain-free after 2 weeks (not significant). The time until complete pain relief with pantoprazole or omeprazole, based on data from diary cards, was not significantly different (P < 0.05, Uleman's U-test). Both treatments were equally well tolerated. Changes in routine laboratory parameters were minimal in both groups. Conclusion: Pantoprazole was shown to be a highly-effective and well-tolerated treatment for acute duodenal ulcer. Pantoprazole 40 mg and omeprazole 20 mg were equally effective with respect to ulcer healing and pain relief, and have similar adverse event profiles.     

Comparison of the efficacy of pantoprazole vs. nizatidine in the treatment of erosive oesophagitis: a randomized,active-controlled,double-blind study

BACKGROUND: Pantoprazole is a proton pump inhibitor approved for the treatment of erosive oesophagitis and gastro-oesophageal reflux disease. AIM: To compare the efficacy and safety of pantoprazole vs. nizatidine for the treatment of symptomatic gastro-oesophageal reflux disease and endoscopically documented erosive oesophagitis (grade > or = 2). METHODS: A multicentre, double-blind, randomized, active-controlled study (221 patients) was performed to compare 20 and 40 mg pantoprazole daily with nizatidine 150 mg b.d. (maximum, 8 weeks). The primary end-point was endoscopic healing of erosive oesophagitis (grade 1 or 0). The secondary end-point was symptomatic improvement. RESULTS: Healing averaged 61%, 64% and 22% for pantoprazole 20 mg, pantoprazole 40 mg and nizatidine 150 mg, respectively, at 4 weeks, and 79%, 83% and 41% at 8 weeks (P < 0.05, differences between groups at both points). Starting on day 1 of symptom assessment, significantly fewer pantoprazole-treated patients reported night-time heartburn and regurgitation compared with nizatidine-treated patients. Symptoms of gastro-oesophageal reflux disease were completely eliminated in 68% and 65% of patients in the pantoprazole 20-mg and 40-mg groups and in 28% of patients in the nizatidine group at study completion. The difference between each pantoprazole group and the nizatidine group was significant (P < 0.05). CONCLUSIONS: Pantoprazole, at single daily doses of 20 mg and 40 mg for up to 8 weeks, provides more rapid relief of symptoms and superior healing of erosive oesophagitis than nizatidine 150 mg b.d., and is well tolerated.     

A comparison of omeprazole, lansoprazole and pantoprazole in the maintenance treatment of severe reflux oesophagitis

Background:

Proton pump inhibitors are effective for the healing of oesophagitis. Standard doses of omeprazole, lansoprazole or pantoprazole are sufficient for healing in mild to moderate cases of oesophagitis.

Aim:

To compare the efficacy of double the standard doses of omeprazole, lansoprazole or pantoprazole for maintenance treatment of severe oesophagitis complicated by a stricture.

Methods:

Thirty-six patients with reflux oesophagitis and stricture confirmed by endoscopy were included in a prospective study comparing three maintenance therapies. In all cases weekly dilatation of the stenosis was performed and patients were treated with omeprazole 20 mg b.d. until healing of oesophagitis and dysphagia relief were achieved. Thirty participants responded to therapy and were then randomly assigned to 4 weeks of maintenance treatment with omeprazole (20 mg b.d.; n=10), lansoprazole (30 mg b.d.; n=10) or pantoprazole (40 mg b.d.; n=10). Subsequently, endoscopies were performed—the endoscopists were blinded to the therapy assignment. The endpoints were defined as the absence of oesophagitis, oesophageal stricture and complaints.

Results:

After 4 weeks of treatment, the number of patients remaining in remission (no oesophagitis or stricture and no symptoms) was nine out of 10 (90%) in the omeprazole group, two out of 10 (20%) in the lansoprazole group (P < 0.01) and three out of 10 (30%) in the pantoprazole group (P < 0.01).

Conclusions:

In our study omeprazole was superior to either lansoprazole or pantoprazole in the maintenance treatment of complicated gastro-oesophageal reflux disease.

     

Does 40 mg omeprazole daily offer additional benefit over 20 mg daily in patients requiring more than 4 weeks of treatment for symptomatic reflux oesophagitis?

This study was designed to establish whether 40 mg omeprazole once daily exhibits sufficient additional efficacy over that of 20 mg omeprazole once daily in patients with symptomatic reflux oesophagitis requiring more than an initial 4-week course of 20 mg omeprazole once daily (o.m.) to warrant routine use of the higher dose. Three hundred and thirteen patients were randomized to receive either 20 mg omeprazole (4 weeks) then 20 mg (second 4 weeks if not both healed and symptom-free after 4 weeks), or 20 mg omeprazole (4 weeks) then 40 mg omeprazole o.m. (second 4 weeks). One hundred and twenty-seven patients were healed and symptom-free after 4 weeks and left the study at that point. Taking the second treatment period in isolation, the healing rate (64%vs. 45%, P < 0.02) and relief of heartburn (72%vs. 60%, P < 0.002) were greater among patients receiving 40 mg omeprazole o.m., demonstrating the existence of a dose–response relationship for omeprazole. However, on completion, there were no significant differences between the patients randomized to the 20/20 mg (healed 65%, asymptomatic 69%) or the 20/40 mg (healed 74%, asymptomatic 74%: both not significant differences compared with 20/20 mg) regimens. The magnitude of the difference in efficacy between 20 and 40 mg omeprazole in symptomatic reflux oesophagitis is insufficient to warrant the routine use of 40 mg in patients requiring more than 4 weeks' treatment with 20 mg omeprazole o.m.; continued treatment with 20 mg omeprazole for 4–8 weeks is the preferred option.     

Rapid symptom relief in reflux oesophagitis: a comparison of lansoprazole and omeprazole

Background: Lansoprazole, a substituted benzimidazole, is a proton pump inhibitor which is highly effective in the control of 24-h intragastric acidity. The aim of this multicentre, randomized, double-blind study was to compare lansoprazole 30 mg once daily and omeprazole 20 mg once daily in the symptom relief and healing of patients with reflux oesophagitis. Methods: Six hundred and four patients with endoscopically proven oesophagitis and a recent history of heartburn were randomly assigned to receive lansoprazole 30 mg or omeprazole 20 mg daily for 4–8 weeks. Daily assessment of symptoms was made by the patient using a 100-mm Visual Analogue Scale. Clinical symptoms were evaluated at weeks 0, 1, 4 and 8. Endoscopic assessment of healing, defined by normalization of the oesophageal mucosal appearance, was made at weeks 4 and 8. Results: Two hundred and eighty-two patients in the lansoprazole group and 283 patients in the omeprazole group were eligible for inclusion in the per protocol analysis. At 3 days, there was a significant improvement in daytime symptoms of heartburn for patients in the lansoprazole group compared with the omeprazole group (P=0.05). A similar but non-significant trend was seen at 7 days (P=0.18). Clinical assessment at 7 days demonstrated significant improvement in daytime epigastric pain in the lansoprazole group compared with the omeprazole group (P=0.03), with a similar but non-significant trend in night-time epigastric pain (P=0.07). Healing rates of oesophagitis at 4 and 8 weeks were 70 and 87%, respectively, with lansoprazole, and 63 and 82%, respectively, with omeprazole. Logistic regression analysis of the cumulative healing rates, which included baseline factors affecting outcome, resulted in an odds ratio of 1.46 (95% CI=0.87–2.45), suggesting a higher chance of being healed with lansoprazole treatment compared with omeprazole treatment. A total of 615 adverse events were reported by 308 (51%) patients during the study period. The majority of events were mild in nature and the incidence was similar in both treatment groups. The most frequently reported events were headache, diarrhoea and nausea. Conclusion: Lansoprazole provides greater symptom relief compared with omeprazole during the first week of treatment. Both treatments were effective in healing oesophagitis.     

Esomeprazole 20 mg vs. pantoprazole 20 mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study

BACKGROUND: Following initial healing of erosive oesophagitis, most patients require maintenance therapy to prevent relapse. AIM: To compare endoscopic and symptomatic remission rates over 6 months' maintenance therapy with esomeprazole or pantoprazole (both 20 mg once daily) in patients with healed erosive oesophagitis. METHODS: Patients with symptoms of gastro-oesophageal reflux disease and endoscopically confirmed erosive oesophagitis at baseline were randomized to receive esomeprazole 40 mg or pantoprazole 40 mg for up to 8 weeks. Patients with healed erosive oesophagitis and free of moderate/severe heartburn and acid regurgitation at 4 weeks or, if necessary, 8 weeks entered the 6-month maintenance therapy phase of the study. RESULTS: A total of 2766 patients (63% men; mean age 50 years) received esomeprazole 20 mg (n = 1377) or pantoprazole 20 mg (n = 1389) and comprised the intention-to-treat population. Following 6 months of treatment, the proportion of patients in endoscopic and symptomatic remission was significantly greater for those receiving esomeprazole 20 mg (87.0%) than pantoprazole 20 mg (74.9%, log-rank test P < 0.0001). Esomeprazole 20 mg produced a higher proportion of patients free of moderate to severe gastro-oesophageal reflux disease symptoms and fewer discontinuations because of symptoms than pantoprazole 20 mg (92.2% vs. 88.5%, P < 0.001). CONCLUSIONS: Esomeprazole 20 mg is more effective than pantoprazole 20 mg for maintenance therapy following initial healing of erosive oesophagitis and relief of gastro-oesophageal reflux disease symptoms.     

Cost effectiveness of esomeprazole compared with omeprazole in the acute treatment of patients with reflux oesophagitis in the UK

BACKGROUND: Clinical studies have demonstrated that esomeprazole is superior to omeprazole for the acute treatment of reflux oesophagitis. OBJECTIVE: To compare the cost effectiveness of esomeprazole 40mg once daily with omeprazole 20mg once daily in patients with reflux oesophagitis. METHODS: Pooled data were used from three 8-week clinical trials comparing the efficacy and safety of esomeprazole 40mg once daily and omeprazole 20mg once daily for the acute treatment of reflux oesophagitis. A simple decision analysis model, using UK direct medical costs, compared the cost effectiveness of the two treatments. Healing probabilities derived from the clinical studies using the Life Table method were used to estimate the effectiveness and cost of treating 100 patients with reflux oesophagitis. Patient management assumptions were based on a clinical management survey involving 25 UK physicians. PERSPECTIVE: UK National Health Service. RESULTS: After 4 weeks' therapy, the Life Table estimated the oesophageal healing rate to be 77.7% in esomeprazole 40mg once-daily recipients (n = 2446), compared with 67.6% in omeprazole 20mg once-daily recipients (n = 2431; p < 0.001). The corresponding values after 8 weeks' treatment were 93.4% and 86.2%, respectively (p < 0.001). The model predicted that when considering healing probabilities over 8 weeks, esomeprazole 40mg once daily produced total direct cost savings of pound1290 (14%) when compared with omeprazole 20mg once daily. When considering the cost of treating patients who had failed treatment (defined as patient not healed as assessed by endoscopy) after 8 weeks, the cost advantage for esomeprazole was even greater. CONCLUSION: Esomeprazole 40mg once daily is cost effective compared with omeprazole 20mg once daily in the acute treatment of patients with reflux oesophagitis; esomeprazole provides greater effectiveness at a lower cost.     

Lansoprazole versus ranitidine for the treatment of reflux oesophagitis

Background: Lansoprazole is a H⁺, K⁺-ATPase (proton pump) inhibitor with an anti-secretory action and is therefore potentially useful in the treatment of gastro-oesophageal reflux. Methods: This study was conducted to determine the efficacy and short-term safety of lansoprazole at doses of 30 mg or 60 mg once daily, compared with ranitidine 150 mg twice daily, in the treatment of patients with reflux oesophagitis. This was a double-blind, stratified, randomized, comparative, parallel group study conducted in five centres in the UK. A total of 229 patients (155 men) aged 18–79 years with endoscopically-confirmed oesophagitis were randomized to receive lansoprazole 30 mg p.o. daily, lansoprazole 60 mg p.o. daily, or ranitidine 150 mg p.o. b.d. Efficacy was assessed by endoscopic examination at 4 weeks and 8 weeks, together with symptom relief and antacid usage. Results: Lansoprazole 30 mg and 60 mg were superior at 4 and 8 weeks (P < 0.01) to ranitidine in healing reflux oesophagitis: respective healing rates being 84%, 72% and 39% after 4 weeks and 92%, 91% and 53% after 8 weeks. Relief of heartburn with lansoprazole 30 mg and 60 mg was superior to that achieved with ranitidine at both week 4 (P < 0.01) and week 8 (P < 0.02). Sixty-four patients experienced a total of 85 adverse events, one-third of which were considered drug-related. The incidence and severity were similar in the three groups. Conclusion: Lansoprazole 30 mg and 60 mg once daily are more effective than ranitidine 150 mg twice daily in the short-term treatment of reflux oesophagitis.     

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 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.     

Systematic review of proton pump inhibitors for the acute treatment of reflux oesophagitis

BACKGROUND: Esomeprazole is a new proton pump inhibitor, which has been compared to omeprazole for the treatment of reflux oesophagitis in clinical trials. AIM: To compare the effectiveness of esomeprazole with the recommended dose of proton pump inhibitors in the healing of reflux oesophagitis, using omeprazole as a common comparator. METHODS: Systematic review of randomized controlled trials. Extraction and re-analysis of data to provide 'intention-to-treat' results. Meta-analysis using a Fixed Effects model. RESULTS: A meta-analysis of healing rates of esomeprazole 40 mg compared to omeprazole 20 mg gave the following results: at 4 weeks (relative risk 1.14; 95% CI: 1.10, 1.18) and 8 weeks (RR 1.08; 95%CI: 1.05, 1.10). Other proton pump inhibitors compared to omeprazole 20 mg are as follows: lansoprazole 30 mg at 4 weeks (RR 1.02; 95%CI: 0.97, 1.08) and 8 weeks (RR 1.01; 95%CI: 0.97, 1.06); pantoprazole 40 mg at 4 weeks (RR 0.99; 95%CI: 0.91, 1.07) and 8 weeks (RR 0.98; 95%CI: 0.93, 1.04); rabeprazole 20 mg at 4 weeks (RR 1.00; 95%CI: 0.87, 1.14) and 8 weeks (RR 0.98; 95%CI: 0.91, 1.05). CONCLUSIONS: Esomeprazole has demonstrated higher healing rates than omeprazole at 4 and 8 weeks. Other proton pump inhibitors (lansoprazole, pantoprazole and rabeprazole) have not shown higher healing rates when compared with omeprazole.     

Omeprazole is more effective than cimetidine for the relief of all grades of gastro-oesophageal reflux disease-associated heartburn, irrespective of the presence or absence of endoscopic oesophagitis

Background: Previous studies have demonstrated greater efficacy for omeprazole compared with cimetidine in patients with endoscopically verified oesophagitis, but excluded the substantial group of gastro-oesophageal reflux disease (GERD) patients with reflux symptoms but without endoscopic abnormality. This prospective, randomized, double-blind study compared omeprazole and cimetidine in the treatment of GERD-associated heartburn both in patients with symptomatic non-ulcerative oesophagitis and in those with heartburn but without oesophagitis. Methods: A total of 221 patients with heartburn and oesophageal mucosa grade 0 (normal, n = 51), 1 (no macroscopic erosions, n = 52), 2 (isolated erosions, n = 97) or 3 (confluent erosions, n = 21) were randomized to receive double-blind either omeprazole 20 mg daily or cimetidine 400 mg q.d.s. for a period of 4 weeks. Those still symptomatic after 4 weeks of treatment received omeprazole 20 mg daily for a further 4 weeks. Results: There was no correlation between severity of heartburn and endoscopic grade at entry (correlation coefficient = 0.196). After 4 weeks of treatment, the proportion of patients in whom heartburn was controlled (no more than mild symptoms on no more than 1 day in the previous 7) on omeprazole (66%; 74/112) was more than double that on cimetidine (31%; 34/109) (P < 0.0001). There was no significant difference between the relief of heartburn in the 47% of patients without unequivocal oesophagitis (endoscopic grade 0 or 1) and in the 53% of patients with erosive oesophagitis (grade 2 or 3) (P = 0.31). Only treatment with omeprazole (P < 0.0001) and lower severity of heartburn at entry (P < 0.01) were significant in predicting heartburn relief. Amongst those patients requiring an additional 4 weeks of treatment with omeprazole, 67% (54/81) reported that their heartburn was controlled after 8 weeks of treatment. Conclusion: We conclude that omeprazole is superior to cimetidine for the relief of all grades of heartburn in GERD, whether or not the patient has unequivocal endoscopic oesophagitis.     

Clinical trial: factors associated with resolution of heartburn in patients with reflux oesophagitis – results from the EXPO study

Background The ability to predict symptom response to reflux oesophagitis‐healing therapy may optimize treatment decisions. Aim To identify factors associated with heartburn resolution in patients receiving acid‐suppressive therapy for reflux oesophagitis. Methods In this multicentre, randomized, double‐blind trial (EXPO; AstraZeneca study code: SH‐NEG‐0008), patients with endoscopically confirmed reflux oesophagitis and reflux symptoms received once‐daily proton pump inhibitor therapy [esomeprazole 40 mg (n = 1562) or pantoprazole 40 mg (n = 1589)] for ≥4 weeks. Factors associated with heartburn resolution after 4 weeks were identified by multiple logistic regression analysis. Results Esomeprazole therapy, positive Helicobacter pylori status and greater age were associated with an increased likelihood of heartburn resolution [odds ratio (95% confidence interval): 1.31 (1.12, 1.54), 1.44 (1.19, 1.74) and 1.013 (1.007, 1.019) per year, respectively; all P < 0.001]. Men and patients with no acid regurgitation or epigastric pain pre‐treatment were also more likely to achieve heartburn resolution (all P < 0.05). Conclusions The use of esomeprazole rather than pantoprazole increases the probability of achieving resolution of heartburn during reflux oesophagitis‐healing therapy. Other factors, including H. pylori status, age, gender and symptom profile may be helpful in determining the likelihood of heartburn resolution in such patients.     

Double-blind, placebo-controlled comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of erosive or ulcerative gastro-oesophageal reflux disease

Background:

Rabeprazole sodium is the most recent member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing oesophagitis.

Methods:

In this randomised, double-blind, multicentre study, conducted at 27 European sites, the efficacy and safety of rabeprazole and omeprazole were compared in patients with erosive or ulcerative gastro-oesophageal reflux disease (GERD).100 patients received rabeprazole 20 mg, and 102 patients omeprazole 20 mg once daily for 4 or 8 weeks, with healing monitored by endoscopy.

Results:

Overall GERD healing rates observed and evaluated at weeks 4 and 8 were equivalent. Four-week healing rates for rabeprazole and omeprazole were 81%–81% and 92%–94% for 8-week healing. Rabeprazole-treated patients had similar relief of the frequency and intensity of heartburn to those treated with omeprazole. Both drugs were well tolerated over the 8-week treatment period. Mean changes in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen. Biopsies for argyrophil ECL cell histology at the end-point revealed a similar distributions of hyperplasia grades to those at baseline in both groups. Biopsies of body and antral mucosa for other parameters were similar between treatments for Helicobacter pylori colonization, presence or degree of inflammation, atrophy or intestinal metaplasia at the end-point.

Conclusion:

In this study, GERD healing rates following rabeprazole 20 mg once daily were equivalent to those obtained with omeprazole 20 mg once daily. Both treatments resulted in a comparable relief of the frequency and intensity of heartburn associated with this disease, and both were well tolerated.

     

Pantoprazole: a new proton pump inhibitor in the management of upper gastrointestinal disease

Pantoprazole, the third proton pump inhibitor (PPI) to become available, has been extensively investigated. Pantoprazole inhibits acid more powerfully than histamine H(2) receptor antagonists (H(2)RAs) and omperazole 20 mg and raises median 24-h gastric pH from about 1.5 to 3-4 in healthy volunteers and in duodenal ulcer patients to above 5. Results from studies have confirmed that pantoprazole is superior to H(2)RAs in speed of healing and symptom relief in patients with peptic ulcer. In patients with duodenal ulcer pantoprazole was as effective as omperazole 20 mg and in patients with gastric ulcer pantoprazole was statistically superior to omeprazole 20 mg after 4 weeks. In triple combination therapy of peptic ulcer disease, the mean eradication rate of Helicobacter pylori in data pooled from 32 pantoprazole-based studies was 86% and compliance with treatment was about 90%. Results pooled from 5 large clinical trials of gastroesophageal reflux disease showed healing rates significantly superior to those achieved with H(2)RAs and similar to those of other PPIs at 4 and 8 weeks. Symptom relief was more rapid with pantoprazole and maintenance treatment kept the majority of patients in remission; relapse rates at 1 year were 25-28% on 20 mg daily and 6-22% on 40 mg daily. Maintenance treatment with pantoprazole 40 mg has been shown to keep most patients with aggressive or refractory ulcer and reflux disease in remission for up to 3 years. Pantoprazole was also effective in the management of patients with Zollinger-Ellison syndrome. In volunteers given aspirin, pantoprazole 40 mg proved significantly superior to ranitidine and placebo in preventing the development of mucosal damage and was significantly better than placebo in preventing gastric ulcer and duodenal ulcer in arthritic patients on nonsteroidal antiinflammatory drugs. Clinical trials, postmarketing surveillance and long-term studies have confirmed that pantoprazole is effective and safe for the short- and long-term management of peptic ulcer and reflux disease, with side effects similar in incidence and type to those of H(2)RAs.     

Reflux symptom relief with omeprazole in patients without unequivocal oesophagitis

Background : As many as 50% of patients with reflux symptoms have no endoscopic evidence of oesophagitis. This multicentre study was designed to assess symptom relief after omeprazole 20 mg once daily in patients with symptoms typical of gastro-oesophageal reflux disease but without endoscopic evidence of oesophagitis.
Methods : Patients ( n =209) were randomized in a double-blind study to receive either omeprazole 20 mg once daily ( n =98) or placebo ( n =111) for 4 weeks. Symptoms were assessed at clinic visits and using daily diary cards, with patient-completed questionnaires providing additional data on symptoms and on psychological disturbance.
Results : On completion, symptom relief favoured omeprazole: 57% of patients on omeprazole were free of heartburn (vs. 19% on placebo), 75% were free of regurgitation (47%) and 43% were completely asymptomatic (14%), each with P <0.0001. Fewer patients in the omeprazole group required alginate/antacid relief medication ( P <0.05). Symptom relief (time to first heartburn-free day) was more rapid with omeprazole (2 vs. 5 days on placebo; P <0.01). A greater reduction in anxiety occurred in the omeprazole group ( P <0.05).
Conclusion : Omeprazole 20 mg once daily is effective in providing relief of the symptoms typical of gastro-oesophageal reflux disease in patients with essentially normal oesophageal mucosa.     

Pantoprazole 20 mg is effective for relief of symptoms and healing of lesions in mild reflux oesophagitis

Aim:

To investigate the efficacy of a low dose of pantoprazole, a gastric proton pump inhibitor, for the relief of symptoms and healing of lesions in mild gastro-oesophageal reflux disease (GERD), and to compare it with the efficacy of ranitidine.

Methods:

Patients with endoscopically established GERD (Stage I, Savary–Miller classification) were enrolled into a randomized, double-blind, parallel-group and multicentre study (intention-to-treat n = 209, age range 19–82 years). They were treated once daily with oral pantoprazole 20 mg or ranitidine 300 mg, for up to 8 weeks. End-point parameters included relief of symptoms (heartburn, acid regurgitation, pain on swallowing) and the healing of GERD lesions. Relief from symptoms was assessed after 2 and 4 weeks, and endoscopically confirmed healing of lesions after 4 and 8 weeks.

Results:

The proportion of patients reporting complete relief from symptoms after 2 weeks was greater in the pantoprazole than in the ranitidine group (69 vs. 48%, P < 0.01), with further improvements seen in the pantoprazole group after 4 weeks (80 vs. 65%, P < 0.05, Cochran–Mantel/Haenszel test). Healing of lesions was confirmed in 70/87 (80%) patients after 4 weeks (pantoprazole group), as compared with 55/86 (64%) patients (ranitidine group) (P < 0.05, per protocol population); after 8 weeks the respective results were 78/87 (90%) and 63/86 (73%) patients (P < 0.01). Both study medications were well tolerated.

Conclusion:

Low-dose pantoprazole (20 mg) is clinically superior to ranitidine (300 mg) in providing fast relief from symptoms and healing of lesions in patients with mild GERD.