Comparable efficacy of pantoprazole and omeprazole in patients with moderate to severe reflux esophagitis. Results of a multinational study

AIM: To compare the efficacy and tolerability of pantoprazole 40 mg and omeprazole MUPS 40 mg in patients with moderate to severe gastroesophageal reflux disease (GERD). METHODS: In this randomized, double-blind, parallel-group, multicenter study conducted in Austria, Germany, Portugal, Switzerland and The Netherlands, patients with endoscopically confirmed moderate to severe GERD (Savary/Miller esophagitis grade II/III) were enrolled. They received a once-daily dose of either 40 mg pantoprazole or 40 mg omeprazole MUPS. Healing was determined by endoscopy after 4 weeks of treatment. If patients were not healed, treatment was extended for another 4 weeks. An additional endoscopy was performed in these cases after 8 weeks of treatment. Healing was determined by endoscopy after 4 and 8 weeks. In addition, treatment effect on symptoms was evaluated by the investigator using a questionnaire assessing heartburn, reflux regurgitation and pain on swallowing at each visit, as well as by a self-administered questionnaire comprising further 24 gastrointestinal symptoms. Analyses were performed for the intention-to-treat (ITT) and the per-protocol (PP) population. In addition, patients with high compliance (HC: 90% 相似文献   

Efficacy and tolerability of 20 mg pantoprazole versus 300 mg ranitidine in patients with mild reflux-oesophagitis: a randomized, double-blind, parallel, and multicentre study

BACKGROUND AND AIM: The aim of this study was to compare the efficacy and tolerability of low dose pantoprazole (20 mg) (a gastric proton pump inhibitor) with standard dose ranitidine (300 mg) (a histamine-receptor antagonist), in their ability to relieve symptoms and heal oesophageal lesions associated with gastrooesophageal reflux disease (GORD). METHODS: Patients with endoscopically established mild GORD (stage I, modified Savary-Miller classification) were enrolled into a multicentre, randomized, double-blind, parallel-group comparison study (intention-to-treat population, n = 201; age range, 18-82 years). Patients took either oral pantoprazole 20 mg in the morning (n = 101) or ranitidine 300 mg in the evening (n = 100) once daily for 4 weeks or, if the healing was not complete, 8 weeks. Relief from key symptoms (heartburn, acid regurgitation, pain on swallowing) was assessed after 2, 4, and if applicable, 8 weeks. Healing of lesions was confirmed endoscopically after 4 and, if applicable, 8 weeks. RESULTS: Complete relief from key symptoms was noted after 2 weeks in 70/88 (80%) patients treated with pantoprazole vs 45/89 (51%) patients treated with ranitidine ('per-protocol and key-point available' populations, P < 0.001); the corresponding results after 4 weeks were 77/88 (88%) vs 51/88 (58%) (P < 0.001). Complete healing of lesions after 4 weeks of treatment was seen in 74/88 (84%) vs 49/89 (55%) in the pantoprazole and ranitidine group, respectively (P < 0.001, per-protocol); by week 8 the cumulative healing rates were 84/88 (95%) vs 69/89 (78%) in the pantoprazole and ranitidine group, respectively (P < 0.001). For the intention-to-treat populations, the corresponding values for healing after 4 and 8 weeks were 73% vs 49% (P < 0.001) and 83% vs 69% (P < 0.05), respectively. Both study medications were well tolerated. CONCLUSION: Compared to ranitidine 300 mg, the regimen with pantoprazole 20 mg provides faster relief from symptoms and is significantly more effective in healing of oesophageal lesions in patients with mild reflux-oesophagitis. Thus, the low dose of pantoprazole offers a treatment approach which minimizes drug exposure and costs while retaining high efficacy.     

Cure of Helicobacter pylori infection and healing of duodenal ulcer: comparison of pantoprazole-based one-week modified triple therapy versus two-week dual therapy

Objective: Eradication of Helicobacter pylori ( H. pylori ) is recommended as the first-line therapeutic concept for reliable long-term prevention of duodenal ulcer (DU) relapse. Current treatment regimens vary in efficacy, complexity, and compliance. To assess the efficacy of pantoprazole in H. pylori eradication in parallel groups of patients using two eradication regimens.
Methods: Patients, (18–85 yr old; intention-to-treat,  n = 286  ) with proven DU, positive rapid urease test (biopsy), and ¹³C-urea breath test (UBT) were included in a prospective, randomized, multicenter study. Modified triple therapy consisted of 40 mg pantoprazole b.i.d ., 500 mg clarithromycin t.i.d ., and 500 mg metronidazole t.i.d . for 7 days (PCM therapy); dual therapy consisted of 40 mg pantoprazole b.i.d . and 500 mg clarithromycin t.i.d . for 14 days (PC therapy). In both groups 40 mg pantoprazole o.d . was given until day 28 when healing of DU was evaluated endoscopically; H. pylori status was assessed by UBT on day 56.
Results: H. pylori eradication rate was 95% in PCM versus 60% in PC therapy groups (per-protocol population,   p < 0.001  ), and 82% in PCM versus 50% in PC therapy in the intention-to-treat patient population (   p < 0.001  ). The DU healing rate was 98% in the PCM and 95% in the PC therapy groups (per-protocol population). Both regimens were similarly well tolerated. Adverse events in both regimens included taste disturbance, diarrhea, and increased serum concentration of liver enzymes, at an incidence of < 10%.
Conclusions: Compared to 2-wk PC therapy (pantoprazole and clarithromycin), the 1-wk PCM therapy (pantoprazole, clarithromycin, and metronidazole) is a significantly superior and highly promising strategy for eradication of H. pylori .     

Pantoprazole versus lansoprazole in French patients with reflux esophagitis

OBJECTIVES: The aim of this study was to compare the efficacy of pantoprazole 40 mg and lansoprazole 30 mg given for 4 to 8 weeks on endoscopic healing and symptom relief in grade II-III reflux esophagitis patients (according to Savary-Miller classification).METHODS: Four hundred and sixty one patients were included (pantoprazole n=226, lansoprazole n=235) in this prospective, randomized, multicenter double-blind study. Endoscopic control was performed at 4 weeks and at 8 weeks if esophagitis was not healed. RESULTS: In the intention-to-treat analysis, the healing rates at 4 weeks were 81 and 80% in the pantoprazole and lansoprazole groups, respectively (NS), 90 and 86% at 8 weeks (NS). In the per-protocol analysis, the healing rates at 4 weeks were 86% in the 2 groups and at 8 weeks 97% in the pantoprazole group and 93% in the lansoprazole group (NS). The heartburn relief rates at day 14 were 88% and 86% in the pantoprazole and lansoprazole groups, respectively. Only esophagitis grade at entry was shown to be a predictive factor for healing at 4 weeks (P<0.0001). CONCLUSION: This study showed that pantoprazole 40 mg once daily is as effective and well tolerated as lansoprazole 30 mg once daily in the treatment of grade II-III acute reflux esophagitis.     

No clinical benefit of adding cisapride to pantoprazole for treatment of gastro-oesophageal reflux disease

OBJECTIVE: Although a proton pump inhibitor (PPI) and a prokinetic drug are often combined for the medical treatment of gastro-oesophageal reflux disease (GORD), there are few well-conducted clinical studies on the efficacy and tolerability of this therapy. This study investigates whether pantoprazole plus cisapride leads to an additional benefit in comparison to pantoprazole alone. DESIGN AND SETTING: Randomized double-blind prospective multicentre study conducted in patients of 33 hospitals in Ireland, South Africa and the UK. PARTICIPANTS: A total of 350 intention-to-treat (ITT) patients aged 18 years or older with GORD of grade II and III were included in the study. The per-protocol (PP) population comprised 152 patients in the pantoprazole group and 136 in the pantoprazole plus cisapride group. INTERVENTIONS: Patients received either pantoprazole 40 mg once daily or pantoprazole 40 mg once daily plus cisapride 20 mg twice daily. Treatment outcome was assessed after 4 and 8 weeks. The primary criterion was endoscopically confirmed healing after 4 weeks. Additionally, relief of leading symptoms was studied. MAIN OUTCOME MEASURES: The prior null hypothesis was no difference in healing rates between both treatment groups. RESULTS: After 4 weeks of treatment 81% and 82%, and after 8 weeks 89% and 90%, of PP patients treated with pantoprazole or pantoprazole plus cisapride were healed, respectively. Thus, equivalence of the two treatment strategies could be proven. Additionally, improvement of symptom relief showed no significant difference between the two regimens. In contrast to disease grade at baseline, Helicobacter pylori status did not influence the healing rates in our study. Both study medications were tolerated well. CONCLUSION: Addition of cisapride to pantoprazole provides no further benefit in the treatment of GORD.     

One week of treatment with esomeprazole-based triple therapy eradicates Helicobacter pylori and heals patients with duodenal ulcer disease.

BACKGROUND: Proton pump inhibitor (PPI) monotherapy is commonly continued for 3 weeks after Helicobacter pylori eradication with PPI-based triple therapy regimens to ensure duodenal ulcer (DU) healing. This randomized, double-blind, multicentre study evaluated whether only 1 week of triple therapy with the new PPI esomeprazole was sufficient to ensure high rates of ulcer healing and H. pylori eradication. METHODS: A total of 446 H. pylori-positive patients with active DU received twice daily treatment with esomeprazole 20 mg (n = 222) or omeprazole 20 mg (n = 224) in combination with amoxicillin 1 g and clarithromycin 500 mg for 1 week (EAC and OAC, respectively). Patients in the OAC group then received 3 weeks' monotherapy with omeprazole 20 mg once daily; those treated with EAC received placebo. Ulcer healing was assessed by endoscopy on completion of therapy and H. pylori status was assessed by (13)C-urea breath testing and histology 4-6 weeks later. RESULTS: Ulcer healing rates (95% CI) for intention-to-treat and per-protocol populations were: EAC + placebo 91% (87-95%) and 94% (90-97%); OAC + omeprazole 92% (88-95%) and 96% (92-98%). Corresponding H. pylori eradication rates were: EAC + placebo 86% (81-90%) and 89% (84-93%); OAC + omeprazole 88% (83-92%) and 90% (85-93%). Both eradication regimens were well tolerated, and patient compliance was high. CONCLUSIONS: A 1-week regimen of esomeprazole-based triple therapy is sufficient for DU healing and H. pylori eradication in patients with DU disease.     

Comparison of pantoprazole 20 mg to ranitidine 150 mg b.i.d. in the treatment of mild gastroesophageal reflux disease

BACKGROUND: Despite a high prevalence of mild gastroesophageal reflux disease (GERD), few studies investigated efficacy and safety of proton pump inhibitors in this indication. This randomized double-blind study compares pantoprazole to ranitidine in GERD 0 and I, i.e. reflux without esophagitis or with confined lesions only. METHODS: Patients received either pantoprazole 20 mg o.a.d. or ranitidine 150 mg b.i.d. Outcome was assessed after 2 and 4 weeks. Primary criterion was relief of leading symptoms, i.e. heartburn, acid eructation and pain on swallowing, after 4 weeks of treatment. RESULTS: According to the per-protocol (PP) analysis, 69% (100/144) and 80% (115/144) of patients in the pantoprazole group were relieved of leading symptoms after 2 and 4 weeks, respectively. The rates in the ranitidine group were 47% (62/133) and 65% (86/133). Thus, superiority of pantoprazole could be proven. Quality-of-life parameters improved more in the pantoprazole group and patients' assessment of treatment was more favorable. Analysis for Helicobacter pylori status showed infection to lead to higher symptom relief rates. Both study medications were well tolerated. CONCLUSION: Pantoprazole 20 mg demonstrated superior efficacy with faster relief of reflux symptoms and similar tolerability compared to ranitidine 150 mg in the treatment of mild GERD.     

Efficacy and tolerability of pantoprazole versus ranitidine in the treatment of reflux esophagitis and the influence of Helicobacter pylori infection on healing rate

Patients with reflux esophagitis (grade II or III, Savary-Miller, intention-to-treat, n=256, age range 19-82 years) were randomly assigned to a double-blind, double-dummy treatment with either pantoprazole 40 mg once daily or ranitidine 150 mg twice daily. After 4 weeks, each patient was clinically and endoscopically assessed. Failure to heal required a further 4 weeks of treatment and a new evaluation thereafter. After 4 weeks, healing of lesions was confirmed in 63% (69 out of 109) of patients receiving pantoprazole and in 22% (25 out of 113) receiving ranitidine (P < 0.001, per protocol population). After 8 weeks, the cumulative healing rates were 88% and 46%, respectively (P < 0.001). Complete freedom from esophagitis-related symptoms (acid eructation, heartburn, pain while swallowing) was greater in the pantoprazole than in ranitidine group after 2 and 4 weeks (74% vs. 47%; 87% vs. 52%, respectively, P < 0.001). After 4 weeks, the healing rate was 76% in Helicobacter pylori (Hp)-positive vs. 45% in Hp-negative patients treated with pantoprazole (P < 0.01). The Hp status did not influence healing rates in patients treated with ranitidine. The most frequent adverse events in the pantoprazole group were diarrhea and somnolence (2-3% of patients), and in the ranitidine group, headache, diarrhea, dizziness, increase of liver enzymes and pruritus (2-4% of patients). In conclusion, pantoprazole was more effective than ranitidine in the healing rate and relief from reflux esophagitis-associated symptoms, and Hp infection was associated with higher healing rate during therapy with pantoprazole but not with ranitidine.     

40 mg pantoprazole and 40 mg esomeprazole are equivalent in the healing of esophageal lesions and relief from gastroesophageal reflux disease-related symptoms

BACKGROUND: Proton pump inhibitors are regarded as the most effective class of acid suppressive medication for gastroesophageal reflux disease treatment. There is considerable interest regarding the dose equivalence between various proton pump inhibitors. GOALS: To compare the efficacy of pantoprazole and esomeprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms. STUDY: Multicenter, randomized, double-blind study. Patients with gastroesophageal reflux disease grades B/C (Los Angeles classification) received 40 mg pantoprazole daily (n = 113) or 40 mg esomeprazole daily (n = 114). Healing (endoscopy) and relief from gastroesophageal reflux disease-related symptoms (direct questioning) were assessed at first and final visit (after 4, 6, 8, or 10 weeks of treatment). RESULTS: Overall healing in both treatment groups was 88% of patients (intention-to-treat population), 95% (pantoprazole), and 90% (esomeprazole) (per-protocol population); statistically, this indicates "at least equivalence" between treatments. Overall relief from gastroesophageal reflux disease-related symptoms was similar for pantoprazole (55%) and esomeprazole (51%, per-protoco). No correlation between healing and symptom relief was seen. The majority of reported adverse events were assessed as "not related" to the study drug. Pantoprazole and esomeprazole have comparably good safety and tolerability. CONCLUSION: In patients with gastroesophageal reflux disease, 40 mg pantoprazole daily and 40 mg esomeprazole daily are equally effective for healing of esophageal lesions and relieving gastroesophageal reflux disease-related symptoms.     

Comparison of efficacy of pantoprazole alone versus pantoprazole plus mosapride in therapy of gastroesophageal reflux disease: a randomized trial

The present study aimed to compare the efficacy for the therapy of GERD of pantoprazole alone with a combination of pantoprazole and mosapride. The study was a prospective, randomized trial involving 68 patients suffering heartburn and/or regurgitation at least twice a week for 6 weeks. Sixty-one patients consented to be randomized to receive either pantoprazole 40 mg b.i.d. (n = 33, group A) or pantoprazole 40 mg b.i.d. plus mosapride 5 mg t.d.s. (n = 28, group B) for 8 weeks. Twenty-four-hour esophageal pH-metry and endoscopy were conducted at recruitment and endoscopy was repeated at 8 weeks in all the patients studied. There were no differences in symptomatic responses to therapy between the groups (69.7% vs 89.2%; P = 0.11). The mean symptom score after 8 weeks was significantly lower in group B (3.78 +/- 3.62 vs 1.67 +/- 2.09; P = 0.009). Nonerosive esophagitis was present in 29 patients. In patients with nonerosive GERD there was no significant difference in symptomatic response to either regimen (17/20 in group A and 7/9 in group B responded; P = 0.63). In erosive esophagitis, symptomatic responses occurred more frequently in group B, 18/19 (94.7%), than in group A, 6/13 (46.2%; P = 0.003). However endoscopic healing of esophagitis occurred equally with either regimen (6/11, 54.5% in group A; 12/17, 70.5% in group B; P = 0.44). In nonerosive GERD, the addition of mosapride offers no benefit over pantoprazole alone. A combination of pantoprazole and mosapride is more effective than pantoprazole alone in providing symptomatic relief to patients with erosive GERD.     

Efficacy and safety of pantoprazole versus ranitidine in the treatment of patients with symptomatic gastroesophageal reflux disease

BACKGROUND/AIM: Gastroesophageal reflux disease (GERD) is a prevalent disease associated with a high symptom burden and a reduced quality of life. This multicenter, randomized, double-blind study compared relief from key GERD symptoms (heartburn, acid eructation, and pain on swallowing) and from other gastrointestinal symptoms (epigastric pain, vomiting, nausea, flatulence, retching, and retrosternal feeling of tightness) and safety profiles of the proton pump inhibitor pantoprazole and the H2 antagonist ranitidine in patients suffering from symptomatic GERD. METHODS: The patients [338 intention-to-treat (ITT) population; 284 per-protocol (PP) population] received 20 mg pantoprazole (once daily in the morning) plus ranitidine placebo (once daily in the evening; ITT n = 167, PP n = 136) or pantoprazole placebo (once daily in the morning) plus 300 mg ranitidine (once daily in the evening; ITT n = 171, PP n = 148) for 28 days. The primary efficacy criterion (ITT and PP populations) was relief from key GERD symptoms (heartburn, acid eructation, and pain on swallowing) after 28 days of treatment. Secondary criteria (PP) included relief from key GERD symptoms on day 14, relief from all gastrointestinal symptoms on days 14 and 28, and relief from key GERD symptoms on days 14 and 28. Safety evaluations included adverse events and laboratory assessments. RESULTS: Significantly more pantoprazole-treated patients were free from key GERD symptoms at day 28 (68.3%, n = 114) as compared with ranitidine-treated patients (43.3%, n = 74; 95% confidence interval for odds ratio 1.84-4.51). Pantoprazole was also significantly more efficacious in controlling all gastrointestinal symptoms of GERD. By day 28, 51.5% (n = 70) of the pantoprazole-treated patients were completely symptom free versus 31.1% (n = 46) of the ranitidine-treated patients (95% confidence interval for odds ratio 1.45-3.83). Both treatments were well tolerated. CONCLUSION: Pantoprazole is significantly superior to ranitidine in the treatment of key and associated gastrointestinal symptoms of GERD and is well tolerated.     

Efficacy of S-Pantoprazole 20?mg Compared with Pantoprazole 40?mg in the Treatment of Reflux Esophagitis: A Randomized, Double-Blind Comparative Trial

Background

S-isomer (S) pantoprazole is known to be more effective and less dependent on cytochrome 2C19 than R-isomer (R)-pantoprazole.

Aim

The purpose of this study was to compare the efficacy and safety of S-pantoprazole 20?mg versus pantoprazole 40?mg for treatment of reflux esophagitis.

Methods

This multi-center, double-blind, randomized trial enrolled patients with endoscopically documented reflux esophagitis. Patients were assigned to receive either 20?mg S-pantoprazole or 40?mg pantoprazole once daily for 4?weeks. Endoscopy and symptoms were assessed after 4?weeks of treatment. In patients whose reflux esophagitis was not resolved at 4?weeks, treatment was extended to 8?weeks and symptoms were reassessed. Heartburn, chest pain, acid regurgitation, globus, and overall symptoms were rated. The primary efficacy endpoint was healing of esophagitis, and secondary endpoints were symptomatic and endoscopic improvement.

Results

Sixty-seven patients in the S-pantoprazole group (52 male, mean age 51?years) and 62 in the pantoprazole group (61 male, mean age 50?years) were analyzed per protocol. The healing rate of reflux esophagitis was 85?% at 4?weeks and 94?% at 8?weeks in the S-pantoprazole group, which did not differ from those in the pantoprazole group (84 and 97?%, respectively). After treatment, individual and overall gastroesophageal reflux disease (GERD) symptoms and esophagitis improved compared with baseline inflammation in both groups. Intergroup differences in symptoms and endoscopic healing were not significant.

Conclusion

The efficacy and safety of 20?mg S-pantoprazole were comparable to those of 40?mg pantoprazole for treatment of reflux esophagitis and symptomatic improvement of GERD.     

Comparative study of modified-release clarithromycin and immediate-release clarithromycin in the treatment of Helicobacter pylori-associated peptic ulcer disease

BACKGROUND/AIMS: Proton pump inhibitor-based triple therapy containing immediate-release clarithromycin is an important regimen for the eradication of Helicobacter pylori (H. pylori). However, the efficacy of modified-release clarithromycin for the treatment of H. pylori-associated peptic ulcer disease is still unknown. The aims of the study were to compare the efficacy of modified-release clarithromycin and immediate-release clarithromycin on the rates of ulcer healing and eradication of H. pylori. METHODOLOGY: One hundred and sixty-one patients with Helicobacter pylori-associated peptic ulcer were randomized to receive one-week triple therapy with either modified-release clarithromycin 1000mg once daily (AECMR) or immediate-release clarithromycin 500mg twice daily (AECIR) in combination with amoxicillin 1,000mg twice daily (A) and esomeprazole 40mg once daily (E). Post-treatment ulcer healing status and Helicobacter pylori status was determined by endoscopy and 13C urea-breath test at 16 weeks and 8 weeks after completion of triple therapy, respectively. RESULTS: Helicobacter pylori eradication rates were 87.5% and 87.7% for AECMR and AECIR, respectively, in the intent-to-treat analysis. Eradication rates in the per-protocol groups were 90.3% and 91.4% for AECMR and AECIR, respectively. In both the intent-to-treat and per-protocol analyses, the eradication rates were comparable in the AECMR and AECIR groups (p= 1.0 and 1.0, respectively). Ulcer healing rates in the intention-to-treat analysis were 81.3% and 77.8% for AECMR and AECIR, respectively. Ulcer healing rates in the per-protocol analysis were 90.3% and 90.0% for AECMR and AECIR groups, respectively. In both the intention-to-treat and per-protocol analyses, the ulcer healing rates were comparable in the AECMR and AECIR groups (p=0.645 and 0.584, respectively). CONCLUSIONS: Modified-release clarithromycin 1000mg once daily can be used as an alternative to immediate-release clarithromycin 500mg twice daily for the treatment of Helicobacter pylori-associated peptic ulcer disease.     

On-demand therapy with pantoprazole 20 mg as effective long-term management of reflux disease in patients with mild GERD: the ORION trial

AIMS: To compare safety and efficacy of on-demand pantoprazole 20 mg/40 mg versus placebo in the long-term management of patients with mild gastroesophageal reflux disease (GERD) after heartburn relief. METHODS: A total of 634 patients with endoscopically confirmed GERD grade 0/I and heartburn were included. During the acute phase, patients were treated with pantoprazole 20 mg once daily for 4 weeks. Those patients relieved from heartburn entered the long-term phase, and were randomly assigned to either treatment group pantoprazole 20 mg, 40 mg or placebo. Over 6 months, patients took study medication on demand (antacids as rescue medication) and discontinued the drug once symptoms abated. RESULTS: After 4 weeks a total of 87.1%/90.0% of patients were free of heartburn (ITT/PP), and entered the subsequent long-term phase. The perceived average daily symptom load (placebo: 3.93, pantoprazole 20 mg: 2.91, pantoprazole 40 mg: 2.71, ITT) and the number of antacid tablets taken (average number, placebo: 0.68, pantoprazole 20 mg: 0.45, pantoprazole 40 mg: 0.33, ITT) were significantly higher in the placebo than in both pantoprazole groups (p<0.0001), with no statistically significant difference between the two pantoprazole groups. The discontinuation rate due to insufficient control of heartburn was significantly lower in both pantoprazole groups compared to placebo (placebo: 10.9, pantoprazole 20 mg: 2.8, pantoprazole 40 mg: 0.9, ITT). CONCLUSIONS: Our findings favor on-demand treatment with pantoprazole 20 mg for the long-term management of heartburn in patients with uncomplicated GERD (grade 0/I) with superiority to placebo.     

Esophageal cell proliferation in gastroesophageal reflux disease： Clinical-morphological data before and after pantoprazole

AIM： To evaluate esophageal mucosal defense mechanisms at an epithelial level to establish if pantoprazole treatment can induce ultrastructural healing and improvement in the proliferation activity of the esophageal epithelium in gastroesophageal reflux disease （GERD）. METHODS： This was a single-blinded study for pH- monitoring, and histological, ultrastructural and MIB1 immunostaining evaluation. Fifty eight patients with GERD were enrolled and underwent 24 h pH-monitoring and endoscopy. Patients were treated for 12 and 24 mo with pantoprazole. Esophageal specimens were taken for histological and ultrastructural evaluation, before and after the treatment. RESULTS： With transmission electron microscopy, all patients with GERD showed ultrastructural signs of damage with dilation of intercellular spaces （DIS）. After 3 mo of therapy the mean DIS values showed a significant reduction and the mean MIB1-LI values of GERD showed an increase in cell proliferation. A further 3 mo of therapy significantly increased cell proliferation only in the erosive esophagitis （ERD） group. CONCLUSION： Three months of pantoprazole therapy induced ultrastructural healing of mucosal damage in 89% and 93% of ERD and non-erosion patients, respectively. Moreover, long-term pantoprazole treatment may be helpful in increasing the capability for esophageal cell proliferation in GERD, particularly in ERD patients.     

A double-blind study of pantoprazole and ranitidine in treatment of acute duodenal ulcer

Pantoprazole is a new substituted benzimidazole, which is a potent inhibitor of gastric acid secretion by its inhibition of H⁺,K⁺-ATPase. Pantoprazole, 40 mg, was compared with the H₂-receptor antagonist ranitidine, 300 mg, in the healing of acute duodenal ulcer. Two hundred seventy-six patients with endoscopically diagnosed duodenal ulcer were studied in this multicenter double-blind study. Patients were reendoscopied after two weeks of treatment, and those patients whose ulcers remained unhealed were also endoscoped after an additional two weeks of treatment. The primary end point was the complete healing of the ulcer. Demographic characteristics were comparable in both treatment groups. After two weeks of treatment, 90/124 (73%) patients in the pantoprazole group had healed ulcers compared with 57/126 (45%) patients in the ranitidine group (P<0.001, per-protocol analysis). After four weeks, the cumulative healing rates were 92% and 84% in the pantoprazole and ranitidine groups, respectively (P=0.073). Symptoms were also improved at week 2, with 84% and 72% of patients in the pantoprazole and ranitidine groups, respectively, reporting no ulcer pain (P<0.05, per-protocol analysis). Both treatments were well tolerated. This study has confirmed the superiority of pantoprazole compared with ranitidine in the healing of duodenal ulcers and pain relief after two weeks of treatment and has shown pantoprazole to be well tolerated in this indication.This study was sponsored by Byk Gulden, D-78467 Konstanz, Germany.Members of the European Pantoprazole Study Group: Belgium—J. Belaiche, M. Cremer, G, Devis, and A. Elewaut; France—M. Amouretti, M.-A. Bigard, G. Bommelaer, J.-A. Chayvialle, J. Escourrou, Y. Le Quintrec, J.-C. Paris, P. Rampal, J. Sahel, and J.-P. Weill; Italy—F. De Berardinis, G. Delle Fave, M. Frezza, G. Marenco, F. Mazzeo, G. Minoli, A. Saggioro, and S. Vigneri; and The Netherlands—J. Beker, W. Driessen, C. Lamers, and D. Versluis.This work was presented as a poster at the symposium: Management of Acid-Related Diseases: Focus on Pantoprazole, held in Berlin, May 1993.     

The efficacy of the third pump inhibitor--pantoprazole--in the short-term treatment of Chinese patients with duodenal ulcer.

BACKGROUND/AIMS: To study the efficacy and tolerability of pantoprazole 40 mg once daily before breakfast compared with ranitidine 300 mg once daily at bedtime in Chinese patients with duodenal ulcer, and to evaluate the relationship between Helicobacter pylori (H. pylori) clearance and ulcer healing rate. METHODOLOGY: A total of 160 patients (80 in each group) with endoscopically diagnosed, active duodenal ulcers were studied in this randomized double-blind trial. Endoscopy was performed after 2 weeks of treatment. If unhealed, then the patients were re-endoscoped after an additional 2 weeks of similar treatment. RESULTS: The healing rates after 2 and 4 weeks were 61.3% and 97.3%, respectively in the pantoprazole group, and 50.7% and 76.9% in the ranitidine group. The difference between the two groups was significant at 4 weeks (p < 0.01, per protocol analysis). The rate of pain free ulcer was higher in the pantoprazole group than in the ranitidine group at 2 weeks (84.2% vs. 59.6%, p < 0.01). Higher clearance of H. pylori was also observed in the pantoprazole group compared with the ranitidine group at 4 weeks (20% vs. 0%, p = 0.05). The healing rate tended to be higher in patients who were H. pylori-cleared at 2 weeks (p = 0.07) in the pantoprazole group. Both medications were well tolerated without any serious adverse effects. CONCLUSIONS: Pantoprazole 40 mg daily is superior to ranitidine 300 mg daily in the short-term treatment of acute duodenal ulcer in Chinese patients, in terms of ulcer healing and pain relief, and appears to be well-tolerated.     

Symptom relief in gastroesophageal reflux disease: a randomized, controlled comparison of pantoprazole and nizatidine in a mixed patient population with erosive esophagitis or endoscopy-negative reflux disease.

OBJECTIVES: Gastroesophageal reflux disease (GERD) in primary care practice presents symptomatically, and resources to distinguish promptly between erosive esophagitis and endoscopy-negative reflux disease (ENRD) are limited. It is therefore important to determine the roles of proton pump inhibitors and histamine-2-receptor antagonists for first-line symptom-based therapy in patients with erosive esophagitis and ENRD. The aim of this study was to compare pantoprazole 40 mg once daily versus nizatidine 150 mg b.i.d. in a mixed GERD patient population with ENRD or erosive esophagitis (Savary-Miller grades 1-3). METHODS: A 4-wk randomized, double-blind, parallel-group, multicenter study conducted in Canada. Eligible patients had experienced GERD symptoms > or = 4 times weekly for > 6 months. Patients were randomized to pantoprazole 40 mg once daily or nizatidine 150 mg b.i.d.. Endoscopy was performed before randomization and after 4 wk of therapy. RESULTS: Of 220 patients randomized to therapy, 208 were available for a modified intent-to-treat analysis. Erosive esophagitis was present in 125 patients; 35 patients were Helicobacter pylori positive. There was complete symptom relief after 7 days of therapy in 14% of patients on nizatidine and in 40% of those on pantoprazole (p < 0.0001), and after 28 days of treatment in 36% and 63% of patients, respectively (p < 0.0001). After 28 days of treatment, adequate heartburn control was reported by 58% of the nizatidine group and in 88% of the pantoprazole (p < 0.0001); erosive esophagitis healing rates were 44% for nizatidine and 79% for pantoprazole (p < 0.001). Rescue antacid was needed by a greater number of patients using nizatidine than of those using pantoprazole (p < 0.001). H. pylori infection was associated with an increased probability of erosive esophagitis healing. CONCLUSIONS: Pantoprazole once daily was superior to nizatidine b.i.d. in producing complete heartburn relief in a mixed population of GERD patients and in achieving erosion healing. The proportions of patients with complete symptom relief were greater with pantoprazole after 7 days of therapy than with nizatidine after 28 days. The present study data suggest that pantoprazole is a highly effective first-line therapy for the management of gastroesophageal reflux disease in a primary care practice setting.     

Dose-range finding study with the proton pump inhibitor pantoprazole in acute duodenal ulcer patients.

Pantoprazole is a newly developed benzimidazole derivative with strong inhibitory actions on gastric acid secretion by blocking H(+)-K(+)-ATPase. This randomized double-blind multicenter trial investigated the efficacy of 20 mg, 40 mg and 80 mg pantoprazole o.m. on ulcer healing and symptomatic relief in 219 out-patients with endoscopically assessed acute duodenal ulcer. After 2 weeks complete ulcer healing was achieved in 58%, 89% and 82% of the patients with 20 mg, 40 mg and 80 mg pantoprazole o.m., respectively. After 4 weeks, corresponding figures were 93%, 99% and 100%; the difference of the healing rates between the 20 mg and 40 mg groups at 2 weeks was statistically significant (p < 0.0001). A rapid pain relief was achieved in all treatment groups: 72% of the 20 mg group, 89% of the 40 mg group, and 84% of the 80 mg group were pain-free after 2 weeks. The difference between 20 mg and 40 mg was statistically significant (p < 0.05). Pantoprazole was well tolerated. Adverse events occurred in 13 patients; headache, skin alterations, and diarrhea were reported most frequently. Severity and frequency of adverse events did not reveal any dose-dependence. In conclusion, pantoprazole provides fast healing of acute duodenal ulcer as well as rapid improvement of ulcer symptoms. For further clinical trials in peptic ulcer disease a daily dose of pantoprazole 40 mg o.m. is recommended.     

Relapse prevention in reflux oesophagitis with regard to Helicobacter pylori status: a double-blind, randomized, multicentre trial to compare the efficacy of pantoprazole versus ranitidine

OBJECTIVE: To compare prospectively the effectiveness of 1 year's treatment with pantoprazole versus ranitidine in order to prevent relapse after initial cure of reflux oesophagitis. For the first time the influence of the initial Helicobacter pylori status on therapeutic results was also taken into account. METHODS: In order to cure reflux oesophagitis, 396 patients with Savary/Miller stage II or III reflux oesophagitis were treated with pantoprazole 40 mg once daily for 8 weeks. Those who were H. pylori positive (n = 140) were also given 1 week of eradication treatment with clarithromycin 2 x 250 mg daily, metronidazole 2 x 400 mg daily, and a further 40 mg pantoprazole daily. The 303 patients who were endoscopically cured after the 8-week period were randomized and treated with either pantoprazole 20 mg (n = 199) or ranitidine 150 mg (n = 104) daily in double-blind fashion. The primary objective was to assess the time to endoscopically proven recurrence of reflux oesophagitis. RESULTS: In the intention-to-treat (ITT) population, 66.3% (118/178) of the pantoprazole group and 34.0% (32/94) of the ranitidine group showed neither endoscopic nor clinical symptoms of relapse after the 1-year treatment period (P < 0.0001) (per-protocol populations: 70.3% [109/155] in the pantoprazole group and 39.4% [28/71] in the ranitidine group). In the pantoprazole group, the relapse rate in initially H. pylori-positive patients who underwent eradication was 30.9% (17/55) and in H. pylori-negative patients 29% (29/100). CONCLUSIONS: Long-term treatment with 20 mg pantoprazole daily to prevent relapse of reflux oesophagitis in H. pylori-negative patients is significantly more effective than 150 mg ranitidine daily. The initial H. pylori eradication treatment does not influence the outcome of the long-term treatment.