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Pantoprazole 20 MG is as effective as pantoprazole 40 MG in prevention of relapse of reflux esophagitis
April1998
Esophageal, Gastric, and Duodenal Disorders A259
days (LAA-3) (21 patients, 13 M, 8 F, age 20-65 years). Eradication was evaluated at 4-8 weeks after cessation of therapy and calculated per-protocol and by intention-to-treat. Results: Seven patients (LAC-7 n=3, LAC-3 n=2, LAA-3 n=2) refused post-treatment endoscopy and were lost to follow-up. All therapeutic regimens were associated with excellent compliance ( > 90% tablets) and none of the patients interrupted therapy because of side effects. LAC-7 LAC-3 Patients (n) 44 23 Eradication per protocol 87.8% 57.1%a (%) (95%-CI) (77-98%) (34-80%) Eradication intention-to81.8% 52.2%a treat (%) (95%-CI) (70-94%) (30-74%) Mild side effects (%) 15% 14% a p < 0.01 vs. LAC-7; b p < 0.001 VS. LAC-7.
LAA-3 21 47.4% b (23-72%) 42.9% a (20-66%) 11%
Conclusions: 1) Triple therapy for three days is associated with significantly lower eradication rate than one-week triple therapy; 2) One-week triple therapy is well tolerated with similar side effects and compliance as threedays therapy; 3) Azithromycin or clarithromycin have similar cure rate using a three-days course; 4) According to our data, short course of triple therapy for HP eradication should not be recommended. Highest eradication was achieved with proton pump inhibitor, amoxicillin and clarithromycin for one week. • GI064
PANTOPRAZOLE, AMOXYCILLIN AND METRONIDAZOLE IN HELICOBACTER PYLORI-POSITIVE DUODENAL ULCER PATIENTS: EFFECTS ON SYMPTOMS, ULCER HEALING AND ERADICATION RATES. A. Pilotto, M Francescbi, L. Bierti*, R. Di Battista*, G. Leandro°, A. Notarbartolo ^, G. Pisciotta^, A. Grassi§, G. Tafner*, S. Michelagnolio and F. Garotta-. Dept. of Geriatrics of Vicenza; Inst. of Intern. Med, Univ. of *Milan; ^ Palermo; § Dept. Med. of Bassano, *S. Camillo Hosp. Trento, olRCCS, Castellana Grotte (BA), *Med. Dept. Pharmacia & Upjohn Milan, Italy. With the aim to evaluate the efficacy and tolerability of a new one-week triple therapy regimen consisting of pantoprazole, plus amoxycillin and metronidazole we studied 51 patients (M=30, F=21, mean age=52.5 years, range=24-75) affected with endoscopically documented duodenal ulcer (DU) in active phase. At the beginning of the study all subjects were Hp-positive, as documented by antra] and body gastric histology (ematoxylin/eosin and Giemsa modified methods), rapid urease test and ]3C urea breath test. All patients were consecutively treated with pantoprazole 40mg daily+amoxycillin lg tid+metronidazole 250mg tid for one week; during the second week patients received pantoprazole 40 mg once in the morning. A clinical diary for everyday assessment of symptoms and side effects was filled by patients during treatment period. Serum laboratory tests were performed before and 8 weeks after treatment. Clinical assessment, endoscopy (with gastric biopsies), rapid urease test and 13C UBT were repeated 8 weeks after the beginning of the study. Results: 3 patients dropped out of the study, 1 due to side effects (glossitis) and 2 due to protocol violation. With therapy a significant rapid decrease in dally and nocturnal epigastric pain was observed (respectively 48.9% and 74.2% after 2 days, 60% and 83.3% after 3 days of treatment, p < 0.001); symptom relief persisted after 8 weeks independently from the Hp status. Two months after therapy, DU healed in 47 out of 48 patients (97.9%, 95%CI=93.9-1). The eradication rates, expressed using intention-to-treat (IT'I') and per protocol (PP) analyses were respectively 80.4% (95%CI=69.5-91.3) and 85.4% (95%CI=75.4-95.4). Hp-cured patients showed a significant decrease in the histological activity of both antral (p=0.0001) and body gastritis (p < 0.008). 15 patients reported 17 adverse events that were mostly mild to moderate; no significant changes in serological parameters occurred. In conclusion one-week triple-therapy with pantoprazole associated with amoxycillin and metronidazole is well tolerated and highly effective to rapidly improve symptoms, heal DU, cure Hp infection and reduce chronic gastritis activity. This study was funded by Pharmacia & Upjohn, Milan, Italy G1065
INHIBITION OF PENTAGASTRIN-INDUCED GASTRIC ACID HYPERSECRETION BY SINGLE-DOSE INTRAVENOUS PANTOPRAZOLE COMPARED WITH SINGLE-DOSE INTRAVENOUS FAMOTIDINE AND PLACEBO IN HEALTHY SUBJECTS. JR Pisegna, M Huang, C Asvar, EA Lew, P Martin, T Kovacs, GV Ohning, JH Walsh, and J Paul. CURE: Digestive Diseases Research Center, West L A V A and UCLA Medical Center, Los Angeles, CA, and Wyeth-Ayerst Research, Philadelphia, PA. Pantoprazole (PANTO) is a newly developed proton pump inhibitor that is being investigated in both oral and intravenous dosage forms for controlling acid hypersecretion in Zollinger-Ellison Syndrome (ZES) and gastroesophageal reflux disease (GERD). The aims of this study were to compare the efficacy and duration for suppression of pentagastrin-stimulated gastric acid output (AO) by IV PANTO compared to IV famotidine (FAM), an H2-receptor antagonist, and placebo, in 23 normal subjects. METHODS: Subjects received continuous pentagastrin infusions (1 tag/kg/h, 25 h) to
stimulate maximal acid output (MAO). After 1 hour (t=0), each subject received a single dose of study drug or placebo, after which AO was measured every 30 minutes using the titration method (0.2 N NaOH). RESULTS: Mean ± SEM) IV PANTO IV PANTO (n = 8) (n = 7) Dose (mg) 40 80 MAO (mEq/h) 44.75 ± 7.80 38.61 ± 9.13 [range] [19.98, 78.70] [18.26, 84.84] Time to AO<10 rnEq/h 1.25±0.29 0.86±0.09 [range] (h) [0.25, 2.5] [0.50, 1.251 Duration, AO
IV Famotidine (n = 4) 20 41.86 ± 11.87 [14.15, 71.97] 0.50±0.10 [0.25, 0.75] 6.38 :e 0.95 [4.5, 8.25]
For placebo-treated subjects (n=4), baseline MAO was 57.7 _+7.77 mEq/h (range: 37.81, 70.26), and average hourly AO (hours 1-24) was 53.73 +_4.31 mEq/h (range: 43.48, 63.99), indicating that there was no desensitization in pentagastrin-induced AO for up to 24 hours. The MAO between each of the study groups was not significantly different (P=0.2). The time to AO < 10 mEq/h was not significantly different for IV PANTO vs. IV FAM groups, however IV PANTO 40 mg and 80 mg groups had a longer duration of action compared to the IV FAM group. These data indicate that IV PANTO 40 mg and 80 mg reduce AO levels as quickly and potently as 20 mg IV FAM ( < 2 h), but have a longer duration of action ( > 15 h). These results indicate that IV PANTO is preferable to IV FAM for acutely managing gastric acid secretion and provide important insights into dosing regimens that will effectively control AO in patients with ZES and GERD. Supported by a grant from Wyeth-Ayerst Research. • G1066
PANTOPRAZOLE 20 MG IS AS EFFECTIVE AS PANTOPRAZOLE 40 MG IN PREVENTION OF RELAPSE OF REFLUX ESOPHAGITIS. K. Plein, J. Hotz, H. Wurzer,§ I. Fumagalli,* H. Tenor,* A. Schneider.* General Hospital Celle, Germany, §University Hospital Graz, Austria, ~Medical Center, Locarno, Switzerland, and *Byk Gulden, Constance, Germany. AIM: To compare the efficacy and safety of pantoprazole (PAN) 40 mg and 20 mg as a relapse prophylaxis in patients with reflux esophagitis (GERD) previously healed with proton pump inhibitors. METHODS: Patients with GERD Savary/Miller stage II or III previously healed on PAN 40 mg or OME 20 mg for 4-8 weeks in a multi-center study in Germany, Austria and Switzerland were randomised to receive, double-blind, either 20 mg or 40 mg PAN once daily for 1 year. Follow-up visits were at 3 month intervals with endoscopies at 6 and 12 months or when patients perceived GERD symptoms on at least 3 consecutive days. The primary parameter was time until endoscopically proven relapse of GERD and secondary parameters were time until symptomatic relapse, laboratory values and adverse events. RESULTS: 433 patients were included: 221 patients received 20 nag PAN and 212 received 40 mg PAN. Estimated relapse rates (Kaplan-Meier) at 6 and 12 months were 13% and 25% respectively for the 20 mg group and 9 and 22% for the 40 mg group. Based on the 90% confidence interval of the difference of the relapse rates both regimens were inferred to be therapeutically equivalent with respect to a +_20% equivalence range. PAN was also effective in preventing symptomatic relapse, with 12 month relapse rates of 23% and 24% in the 20 mg and 40 mg groups respectively. Therapeutic equivalence of both treatment groups was also determined using the above method. Adverse events (AE) were reported by 48 (22%) and 50 (24%) patients in the 20 mg and 40 mg groups respectively: 4 (20 rag) and 7 (40 mg) were considered to be possibly related to study medication, and 1 in each group considered to be definitely related. Most common AE were abdominal pain (n=8), and diarrhea, dizziness, bronchitis, upper respiratory infection and backpain (all n=6). In the whole collective, 18 serious AE were recorded but all were considered as unrelated to PAN. No clinically relevant laboratory values assessed to be related to PAN were observed. Median gastrin values reached maximums of 91.3 ng/1 and 103.8 ng/l from baselines of 57.4 ng/1 and 54.4 ng/1 in the 20 mg and 40 mg groups respectively. CONCLUSIONS: Pantoprazole is effective and safe for maintaining endoscopic and symptomatic remission in patients with healed reflux esophagitis. Doses of 20 mg and 40 mg are therapeutically equivalent. This study was sponsored by Byk Gulden.
Esophageal, Gastric, and Duodenal Disorders A259
days (LAA-3) (21 patients, 13 M, 8 F, age 20-65 years). Eradication was evaluated at 4-8 weeks after cessation of therapy and calculated per-protocol and by intention-to-treat. Results: Seven patients (LAC-7 n=3, LAC-3 n=2, LAA-3 n=2) refused post-treatment endoscopy and were lost to follow-up. All therapeutic regimens were associated with excellent compliance ( > 90% tablets) and none of the patients interrupted therapy because of side effects. LAC-7 LAC-3 Patients (n) 44 23 Eradication per protocol 87.8% 57.1%a (%) (95%-CI) (77-98%) (34-80%) Eradication intention-to81.8% 52.2%a treat (%) (95%-CI) (70-94%) (30-74%) Mild side effects (%) 15% 14% a p < 0.01 vs. LAC-7; b p < 0.001 VS. LAC-7.
LAA-3 21 47.4% b (23-72%) 42.9% a (20-66%) 11%
Conclusions: 1) Triple therapy for three days is associated with significantly lower eradication rate than one-week triple therapy; 2) One-week triple therapy is well tolerated with similar side effects and compliance as threedays therapy; 3) Azithromycin or clarithromycin have similar cure rate using a three-days course; 4) According to our data, short course of triple therapy for HP eradication should not be recommended. Highest eradication was achieved with proton pump inhibitor, amoxicillin and clarithromycin for one week. • GI064
PANTOPRAZOLE, AMOXYCILLIN AND METRONIDAZOLE IN HELICOBACTER PYLORI-POSITIVE DUODENAL ULCER PATIENTS: EFFECTS ON SYMPTOMS, ULCER HEALING AND ERADICATION RATES. A. Pilotto, M Francescbi, L. Bierti*, R. Di Battista*, G. Leandro°, A. Notarbartolo ^, G. Pisciotta^, A. Grassi§, G. Tafner*, S. Michelagnolio and F. Garotta-. Dept. of Geriatrics of Vicenza; Inst. of Intern. Med, Univ. of *Milan; ^ Palermo; § Dept. Med. of Bassano, *S. Camillo Hosp. Trento, olRCCS, Castellana Grotte (BA), *Med. Dept. Pharmacia & Upjohn Milan, Italy. With the aim to evaluate the efficacy and tolerability of a new one-week triple therapy regimen consisting of pantoprazole, plus amoxycillin and metronidazole we studied 51 patients (M=30, F=21, mean age=52.5 years, range=24-75) affected with endoscopically documented duodenal ulcer (DU) in active phase. At the beginning of the study all subjects were Hp-positive, as documented by antra] and body gastric histology (ematoxylin/eosin and Giemsa modified methods), rapid urease test and ]3C urea breath test. All patients were consecutively treated with pantoprazole 40mg daily+amoxycillin lg tid+metronidazole 250mg tid for one week; during the second week patients received pantoprazole 40 mg once in the morning. A clinical diary for everyday assessment of symptoms and side effects was filled by patients during treatment period. Serum laboratory tests were performed before and 8 weeks after treatment. Clinical assessment, endoscopy (with gastric biopsies), rapid urease test and 13C UBT were repeated 8 weeks after the beginning of the study. Results: 3 patients dropped out of the study, 1 due to side effects (glossitis) and 2 due to protocol violation. With therapy a significant rapid decrease in dally and nocturnal epigastric pain was observed (respectively 48.9% and 74.2% after 2 days, 60% and 83.3% after 3 days of treatment, p < 0.001); symptom relief persisted after 8 weeks independently from the Hp status. Two months after therapy, DU healed in 47 out of 48 patients (97.9%, 95%CI=93.9-1). The eradication rates, expressed using intention-to-treat (IT'I') and per protocol (PP) analyses were respectively 80.4% (95%CI=69.5-91.3) and 85.4% (95%CI=75.4-95.4). Hp-cured patients showed a significant decrease in the histological activity of both antral (p=0.0001) and body gastritis (p < 0.008). 15 patients reported 17 adverse events that were mostly mild to moderate; no significant changes in serological parameters occurred. In conclusion one-week triple-therapy with pantoprazole associated with amoxycillin and metronidazole is well tolerated and highly effective to rapidly improve symptoms, heal DU, cure Hp infection and reduce chronic gastritis activity. This study was funded by Pharmacia & Upjohn, Milan, Italy G1065
INHIBITION OF PENTAGASTRIN-INDUCED GASTRIC ACID HYPERSECRETION BY SINGLE-DOSE INTRAVENOUS PANTOPRAZOLE COMPARED WITH SINGLE-DOSE INTRAVENOUS FAMOTIDINE AND PLACEBO IN HEALTHY SUBJECTS. JR Pisegna, M Huang, C Asvar, EA Lew, P Martin, T Kovacs, GV Ohning, JH Walsh, and J Paul. CURE: Digestive Diseases Research Center, West L A V A and UCLA Medical Center, Los Angeles, CA, and Wyeth-Ayerst Research, Philadelphia, PA. Pantoprazole (PANTO) is a newly developed proton pump inhibitor that is being investigated in both oral and intravenous dosage forms for controlling acid hypersecretion in Zollinger-Ellison Syndrome (ZES) and gastroesophageal reflux disease (GERD). The aims of this study were to compare the efficacy and duration for suppression of pentagastrin-stimulated gastric acid output (AO) by IV PANTO compared to IV famotidine (FAM), an H2-receptor antagonist, and placebo, in 23 normal subjects. METHODS: Subjects received continuous pentagastrin infusions (1 tag/kg/h, 25 h) to
stimulate maximal acid output (MAO). After 1 hour (t=0), each subject received a single dose of study drug or placebo, after which AO was measured every 30 minutes using the titration method (0.2 N NaOH). RESULTS: Mean ± SEM) IV PANTO IV PANTO (n = 8) (n = 7) Dose (mg) 40 80 MAO (mEq/h) 44.75 ± 7.80 38.61 ± 9.13 [range] [19.98, 78.70] [18.26, 84.84] Time to AO<10 rnEq/h 1.25±0.29 0.86±0.09 [range] (h) [0.25, 2.5] [0.50, 1.251 Duration, AO
IV Famotidine (n = 4) 20 41.86 ± 11.87 [14.15, 71.97] 0.50±0.10 [0.25, 0.75] 6.38 :e 0.95 [4.5, 8.25]
For placebo-treated subjects (n=4), baseline MAO was 57.7 _+7.77 mEq/h (range: 37.81, 70.26), and average hourly AO (hours 1-24) was 53.73 +_4.31 mEq/h (range: 43.48, 63.99), indicating that there was no desensitization in pentagastrin-induced AO for up to 24 hours. The MAO between each of the study groups was not significantly different (P=0.2). The time to AO < 10 mEq/h was not significantly different for IV PANTO vs. IV FAM groups, however IV PANTO 40 mg and 80 mg groups had a longer duration of action compared to the IV FAM group. These data indicate that IV PANTO 40 mg and 80 mg reduce AO levels as quickly and potently as 20 mg IV FAM ( < 2 h), but have a longer duration of action ( > 15 h). These results indicate that IV PANTO is preferable to IV FAM for acutely managing gastric acid secretion and provide important insights into dosing regimens that will effectively control AO in patients with ZES and GERD. Supported by a grant from Wyeth-Ayerst Research. • G1066
PANTOPRAZOLE 20 MG IS AS EFFECTIVE AS PANTOPRAZOLE 40 MG IN PREVENTION OF RELAPSE OF REFLUX ESOPHAGITIS. K. Plein, J. Hotz, H. Wurzer,§ I. Fumagalli,* H. Tenor,* A. Schneider.* General Hospital Celle, Germany, §University Hospital Graz, Austria, ~Medical Center, Locarno, Switzerland, and *Byk Gulden, Constance, Germany. AIM: To compare the efficacy and safety of pantoprazole (PAN) 40 mg and 20 mg as a relapse prophylaxis in patients with reflux esophagitis (GERD) previously healed with proton pump inhibitors. METHODS: Patients with GERD Savary/Miller stage II or III previously healed on PAN 40 mg or OME 20 mg for 4-8 weeks in a multi-center study in Germany, Austria and Switzerland were randomised to receive, double-blind, either 20 mg or 40 mg PAN once daily for 1 year. Follow-up visits were at 3 month intervals with endoscopies at 6 and 12 months or when patients perceived GERD symptoms on at least 3 consecutive days. The primary parameter was time until endoscopically proven relapse of GERD and secondary parameters were time until symptomatic relapse, laboratory values and adverse events. RESULTS: 433 patients were included: 221 patients received 20 nag PAN and 212 received 40 mg PAN. Estimated relapse rates (Kaplan-Meier) at 6 and 12 months were 13% and 25% respectively for the 20 mg group and 9 and 22% for the 40 mg group. Based on the 90% confidence interval of the difference of the relapse rates both regimens were inferred to be therapeutically equivalent with respect to a +_20% equivalence range. PAN was also effective in preventing symptomatic relapse, with 12 month relapse rates of 23% and 24% in the 20 mg and 40 mg groups respectively. Therapeutic equivalence of both treatment groups was also determined using the above method. Adverse events (AE) were reported by 48 (22%) and 50 (24%) patients in the 20 mg and 40 mg groups respectively: 4 (20 rag) and 7 (40 mg) were considered to be possibly related to study medication, and 1 in each group considered to be definitely related. Most common AE were abdominal pain (n=8), and diarrhea, dizziness, bronchitis, upper respiratory infection and backpain (all n=6). In the whole collective, 18 serious AE were recorded but all were considered as unrelated to PAN. No clinically relevant laboratory values assessed to be related to PAN were observed. Median gastrin values reached maximums of 91.3 ng/1 and 103.8 ng/l from baselines of 57.4 ng/1 and 54.4 ng/1 in the 20 mg and 40 mg groups respectively. CONCLUSIONS: Pantoprazole is effective and safe for maintaining endoscopic and symptomatic remission in patients with healed reflux esophagitis. Doses of 20 mg and 40 mg are therapeutically equivalent. This study was sponsored by Byk Gulden.