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Efficacy of pantoprazole in healing reflux oesophagitis both in presence and absence of Helicobacter pylori
A14 AGA ABSTRACTS
318
SPONTANEOUS ADVERSE EVENT REPORTS OF SERIOUS VENTRICULAR ARRHYTHMIAS, QT PROLONGATION, SYNCOPE, AND SUDDEN DEATH IN PATIENTS TREATED WITH CISAPRIDE: AN ONGOING INDEPENDENT CASE REVIEW. Jean T. Barbey, Ralph Lazzara, Douglas P. Zipes, Georgetown Univ Med Ctr, Washington, DC; Univ of Oklahoma Health Sci Ctr, Oklahoma City, OK; Indiana Univ Sch of Medicine, Indianapolis, IN. Adverse cardiac events have been reported in patients receiving cisapride. We conducted an independent case review of all spontaneous adverse event reports of serious ventricular arrhythmias (SVAs) and QT prolongation (t QT) and of clinical events possibly due to SVAs in patients treated with the prokinetic agent, classifying cases by confidence in diagnosis (dx) and presence of cofactors. We assigned confidence in dx conservatively (erring on side of dx of LQTS), and decisions were made solely by us, without company involvement. Of 471 cases reported worldwide from December 1990 through March 1999, 327 (69%) cases of LQTS or t QT were identified; in 83 (18%) no LQTS or t QT was identified and in 61 (13%) there were insufficient data to assess LQTS. In most of the 327 LQTS or t QTcases, we had high (122,51% ofLQTS cases) or medium (77, 32%) confidence in LQTS dx; 86 (26%) had only t QT. Recognized cofactors were present in 222 (68%) t QT or LQTS cases. The percentage of LQTS cases with cofactors rose with confidence level (P<.OOI): Recognized cofactors were present in 100 (82%) cases with high confidence LQTS and 54 (70%) with medium confidence, versus 14 (33%) with low confidence. The most common recognized cofactors in t QT or LQTS were coadministration of medications that increase cisapride levels by inhibiting cytochrome P450 3A4 (97 cases, 44%), electrolyte disturbances (69, 31%), and concomitant QT prolonging drugs (54, 24%). Of cases in which cytochrome P450 3A4 inhibitors were coadministered, clarithromycin, erythromycin, or fluconazole, or a combination of these drugs, was administered in 79 (81%). Other medical conditions cited as contraindications in labeling (eg, heart failure) were uncommon sole cofactors (45,14%). Of 34 (14%) LQTS cases without cofactors, 9 (4%) were designated high-confidence. Most patients with high confidence dx LQTS and no cofactors or other labeled conditions had complex medical histories. We conclude that in the vast majority of cases of LQTS in patients receiving cisapride, recognizable and often preventable cofactors are present and that LQTS risk diminishes when this drug is used appropriately. Additional data and analysis from this ongoing study will be presented. 319
EFFICACY OF PANTOPRAZOLE IN HEALING REFLUX OESOPHAGITIS BOTH IN PRESENCE AND ABSENCE OF HELICOBACTER PYLORI. Enrico Roda, Franco Bazzoli, Univ of Bologna, Bologna, Italy; On Behalf of Italaian Study Group, Univ of Bologna, Bologna, Italy. Background. The relation between Helicobacter pylori (H.p.) infection and GORD is still unclear. The therapeutic success of the antisecretory drugs in healing reflux oesophagitis has been related to their capability of increasing intragastric pH. Since it has been shown that intragastric pH is higher during PPJ therapy in H.p. +ve than in H.p.-ve patients, the presence of H. p. infection could increase the efficacy of PPls in the treatment of reflux oesophagi tis. Aim. To evaluate the efficacy of Pantoprazole 40 mg o.d. in the treatment of the reflux oesophagitis both in presence or absence of H.p. Methods. 30 I patients (61.1 % males; mean age 46.1 + 15.4 yrs, range 19-83 yrs) with reflux oesophagitis (Grade I-III Savary-Miller) were enrolled in a multicentre, randomised, double-blind, controlled study. All patients received Pantoprazole 40 mg o.d. for 8 weeks; cured patients were randomized to a maintenance phase receiving either pantoprazole 40 mg or 20 mg daily for 12 months (ongoing phase). Upper GI endoscopy was performed before and after the end of the acute therapy. At entry, H.p. status (histology, RUT and l3C-urea breath test) was also assessed. Patients with H.p. infection were randomized to receive additional antimicrobial treatment with clarithromyicin 250 mg b.i.d, + tinidazole 500 mg b.i.d. for I week, or no treatment. GORD symptoms were evaluated before and after 4 and 8 weeks of therapy. Results. 286 out of 30 I patients completed the study and were evaluated. After 2 months, overall, 275 out of 286 patients (96.2%) were healed: of these, 134/143 (94%) were affected by grade I oesophagitis at entry, 131/133 (98.5%) by grade II oesophagitis and 9/10 (90%) by grade III oesophagitis. At entry 32.2% of patients were H.p.+ve. Oesophagitis healing rate was not influenced by H.p. status or by anti-H.p. treatment (96.7% H.p. ve, 95.9% H.p.+ve and 94.3% in those who received antibiotic treatment). After 4 and 8 weeks of treatment patients completely free from heartburn accounted for 83.9% and 90% respectively, these figures being 74.3% and 84.8%, when the all GORD symptoms (acid regurgitation, epigastric pain, dysphagia, heartburn) were considered. The
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improvement of GORD symptoms was independent of H.p. status. Conclusions. Pantoprazole 40 mg od for 8 weeks is highly effective in healing reflux oesophagitis. The H. pylori status or antimicrobial treatment do not influence the efficacy of PPI therapy.
320 PANTOPRAZOLE PREVENTS RELAPSE OF HEALED EROSIVE ESOPHAGITIS IN PATIENTS MORE EFFECTIVELY THAN RA· NITIDINE, REGARDLESS OF BASELINE SYMPTOMATOLOGY. Wieslaw 1. Bochenek, Robert S. Northington, David Miska, David Miska, David C. Metz, Wyeth-Ayerst Research, Radnor, PA; Univ of Pennsylvania Med Ctr, Philadelphia, PA; US GERD Pantoprazole Study Group Univ of Pennsylvania Med Ctr, Philadelphia, PA. AIM: The efficacy and safety of pantoprazole (PANTO), a new proton pump inhibitor, were compared with those of ranitidine (RAN), an Hz receptor antagonist, in preventing relapse and providing symptomatic relief in patients healed from erosive esophagitis (EE) grade 2:: 2 (Hetzel-Dent scale). METHODS:Gastroesophageal reflux disease (GERD) patients with endoscopically confirmed healed EE received double-blind treatment for up to I year with PANTO 10,20, or 40 mg once daily, or RAN 150mg twice daily. Esophageal erosions (>grade 2), detected endoscopically, indicated relapse. Data from 470 patients were analyzed as to GERD symptoms at baseline. RESULTS: Patients receiving 20 or 40 mg PANTO who were symptom-free at baseline experienced significantly (p
EE Relapse Rates at12Months: Number (%) ofPatients NoGERD Symptoms atbaseline ;" 1GERD Symptom at baseline N Relapsed N Relapsed PANTO 10mg PANT020mg PANT040mg RAN 150 mg
41 40 38 49
22 (537) 6 (15,0)' 6 (15,8)' 37 (75.5)
71 75 79 77
35 (49.3) 28 (37,3)' 11 (13,9)' 43(55.8)
Significantly different from 'RANand PANTO 10mg (p<0,001); 'RAN (p<0,024);' RAN and PANTO 10or20 mg (p<0,002).
321 OMEPRAZOLE 10 MG IN THE TREATMENT OF SYMPTOMATIC GERD : PROGNOSTIC FACTORS ASSOCIATED WITH SYMPTOM RESOLUTION AND RELAPSE. Gilles Bommelaer, Agnes Caekaert, Philippe Barthelemy, CHU ClermontFerrand, ClermontFerrand, France; AstraZeneca, Rueil-Malmaison, France. The aim of this prospective multicenter study performed in France in primary care was to identify the prognostic factors associated with symptom resolution and relapse in GERD patients treated 4 weeks with omeprazole 10 mg. Methods: 2775 patients (age: 55 +/- 14; male: 48%) with at least 2 months heartburn andlor acid regurgitation not relieved by antacids andlor alginates, and no erosive andlor ulcerative esophagitis at upper GI endoscopy performed during the last 12 months were enrolled. Patients were treated with omeprazole 10 mg od during 4 weeks and followed for 3 months thereafter. Symptoms were assessed by the investigator according to a 4 graded Likert scale (none, mild, moderate, severe). Symptom resolution was defined as no heartburn during the last 7 days of treatment. Relapse was defined as occurrence of moderate or severe heartburn andlor acid regurgitation, andlor intake of antisecretory agents or prokinetics, andlor performance of an upper GI endoscopy during followup. Intent to treat analysis included all patients who took at least one dose of study drugs. Step-wise logistic regression was used to identify the following potential prognostic factors: age, gender, BMI, disease history, tobacco and coffee intake, heartburn and regurgitation severity, symptom
318
SPONTANEOUS ADVERSE EVENT REPORTS OF SERIOUS VENTRICULAR ARRHYTHMIAS, QT PROLONGATION, SYNCOPE, AND SUDDEN DEATH IN PATIENTS TREATED WITH CISAPRIDE: AN ONGOING INDEPENDENT CASE REVIEW. Jean T. Barbey, Ralph Lazzara, Douglas P. Zipes, Georgetown Univ Med Ctr, Washington, DC; Univ of Oklahoma Health Sci Ctr, Oklahoma City, OK; Indiana Univ Sch of Medicine, Indianapolis, IN. Adverse cardiac events have been reported in patients receiving cisapride. We conducted an independent case review of all spontaneous adverse event reports of serious ventricular arrhythmias (SVAs) and QT prolongation (t QT) and of clinical events possibly due to SVAs in patients treated with the prokinetic agent, classifying cases by confidence in diagnosis (dx) and presence of cofactors. We assigned confidence in dx conservatively (erring on side of dx of LQTS), and decisions were made solely by us, without company involvement. Of 471 cases reported worldwide from December 1990 through March 1999, 327 (69%) cases of LQTS or t QT were identified; in 83 (18%) no LQTS or t QT was identified and in 61 (13%) there were insufficient data to assess LQTS. In most of the 327 LQTS or t QTcases, we had high (122,51% ofLQTS cases) or medium (77, 32%) confidence in LQTS dx; 86 (26%) had only t QT. Recognized cofactors were present in 222 (68%) t QT or LQTS cases. The percentage of LQTS cases with cofactors rose with confidence level (P<.OOI): Recognized cofactors were present in 100 (82%) cases with high confidence LQTS and 54 (70%) with medium confidence, versus 14 (33%) with low confidence. The most common recognized cofactors in t QT or LQTS were coadministration of medications that increase cisapride levels by inhibiting cytochrome P450 3A4 (97 cases, 44%), electrolyte disturbances (69, 31%), and concomitant QT prolonging drugs (54, 24%). Of cases in which cytochrome P450 3A4 inhibitors were coadministered, clarithromycin, erythromycin, or fluconazole, or a combination of these drugs, was administered in 79 (81%). Other medical conditions cited as contraindications in labeling (eg, heart failure) were uncommon sole cofactors (45,14%). Of 34 (14%) LQTS cases without cofactors, 9 (4%) were designated high-confidence. Most patients with high confidence dx LQTS and no cofactors or other labeled conditions had complex medical histories. We conclude that in the vast majority of cases of LQTS in patients receiving cisapride, recognizable and often preventable cofactors are present and that LQTS risk diminishes when this drug is used appropriately. Additional data and analysis from this ongoing study will be presented. 319
EFFICACY OF PANTOPRAZOLE IN HEALING REFLUX OESOPHAGITIS BOTH IN PRESENCE AND ABSENCE OF HELICOBACTER PYLORI. Enrico Roda, Franco Bazzoli, Univ of Bologna, Bologna, Italy; On Behalf of Italaian Study Group, Univ of Bologna, Bologna, Italy. Background. The relation between Helicobacter pylori (H.p.) infection and GORD is still unclear. The therapeutic success of the antisecretory drugs in healing reflux oesophagitis has been related to their capability of increasing intragastric pH. Since it has been shown that intragastric pH is higher during PPJ therapy in H.p. +ve than in H.p.-ve patients, the presence of H. p. infection could increase the efficacy of PPls in the treatment of reflux oesophagi tis. Aim. To evaluate the efficacy of Pantoprazole 40 mg o.d. in the treatment of the reflux oesophagitis both in presence or absence of H.p. Methods. 30 I patients (61.1 % males; mean age 46.1 + 15.4 yrs, range 19-83 yrs) with reflux oesophagitis (Grade I-III Savary-Miller) were enrolled in a multicentre, randomised, double-blind, controlled study. All patients received Pantoprazole 40 mg o.d. for 8 weeks; cured patients were randomized to a maintenance phase receiving either pantoprazole 40 mg or 20 mg daily for 12 months (ongoing phase). Upper GI endoscopy was performed before and after the end of the acute therapy. At entry, H.p. status (histology, RUT and l3C-urea breath test) was also assessed. Patients with H.p. infection were randomized to receive additional antimicrobial treatment with clarithromyicin 250 mg b.i.d, + tinidazole 500 mg b.i.d. for I week, or no treatment. GORD symptoms were evaluated before and after 4 and 8 weeks of therapy. Results. 286 out of 30 I patients completed the study and were evaluated. After 2 months, overall, 275 out of 286 patients (96.2%) were healed: of these, 134/143 (94%) were affected by grade I oesophagitis at entry, 131/133 (98.5%) by grade II oesophagitis and 9/10 (90%) by grade III oesophagitis. At entry 32.2% of patients were H.p.+ve. Oesophagitis healing rate was not influenced by H.p. status or by anti-H.p. treatment (96.7% H.p. ve, 95.9% H.p.+ve and 94.3% in those who received antibiotic treatment). After 4 and 8 weeks of treatment patients completely free from heartburn accounted for 83.9% and 90% respectively, these figures being 74.3% and 84.8%, when the all GORD symptoms (acid regurgitation, epigastric pain, dysphagia, heartburn) were considered. The
GASTROENTEROLOGY Vol. 118, No.4
improvement of GORD symptoms was independent of H.p. status. Conclusions. Pantoprazole 40 mg od for 8 weeks is highly effective in healing reflux oesophagitis. The H. pylori status or antimicrobial treatment do not influence the efficacy of PPI therapy.
320 PANTOPRAZOLE PREVENTS RELAPSE OF HEALED EROSIVE ESOPHAGITIS IN PATIENTS MORE EFFECTIVELY THAN RA· NITIDINE, REGARDLESS OF BASELINE SYMPTOMATOLOGY. Wieslaw 1. Bochenek, Robert S. Northington, David Miska, David Miska, David C. Metz, Wyeth-Ayerst Research, Radnor, PA; Univ of Pennsylvania Med Ctr, Philadelphia, PA; US GERD Pantoprazole Study Group Univ of Pennsylvania Med Ctr, Philadelphia, PA. AIM: The efficacy and safety of pantoprazole (PANTO), a new proton pump inhibitor, were compared with those of ranitidine (RAN), an Hz receptor antagonist, in preventing relapse and providing symptomatic relief in patients healed from erosive esophagitis (EE) grade 2:: 2 (Hetzel-Dent scale). METHODS:Gastroesophageal reflux disease (GERD) patients with endoscopically confirmed healed EE received double-blind treatment for up to I year with PANTO 10,20, or 40 mg once daily, or RAN 150mg twice daily. Esophageal erosions (>grade 2), detected endoscopically, indicated relapse. Data from 470 patients were analyzed as to GERD symptoms at baseline. RESULTS: Patients receiving 20 or 40 mg PANTO who were symptom-free at baseline experienced significantly (p
EE Relapse Rates at12Months: Number (%) ofPatients NoGERD Symptoms atbaseline ;" 1GERD Symptom at baseline N Relapsed N Relapsed PANTO 10mg PANT020mg PANT040mg RAN 150 mg
41 40 38 49
22 (537) 6 (15,0)' 6 (15,8)' 37 (75.5)
71 75 79 77
35 (49.3) 28 (37,3)' 11 (13,9)' 43(55.8)
Significantly different from 'RANand PANTO 10mg (p<0,001); 'RAN (p<0,024);' RAN and PANTO 10or20 mg (p<0,002).
321 OMEPRAZOLE 10 MG IN THE TREATMENT OF SYMPTOMATIC GERD : PROGNOSTIC FACTORS ASSOCIATED WITH SYMPTOM RESOLUTION AND RELAPSE. Gilles Bommelaer, Agnes Caekaert, Philippe Barthelemy, CHU ClermontFerrand, ClermontFerrand, France; AstraZeneca, Rueil-Malmaison, France. The aim of this prospective multicenter study performed in France in primary care was to identify the prognostic factors associated with symptom resolution and relapse in GERD patients treated 4 weeks with omeprazole 10 mg. Methods: 2775 patients (age: 55 +/- 14; male: 48%) with at least 2 months heartburn andlor acid regurgitation not relieved by antacids andlor alginates, and no erosive andlor ulcerative esophagitis at upper GI endoscopy performed during the last 12 months were enrolled. Patients were treated with omeprazole 10 mg od during 4 weeks and followed for 3 months thereafter. Symptoms were assessed by the investigator according to a 4 graded Likert scale (none, mild, moderate, severe). Symptom resolution was defined as no heartburn during the last 7 days of treatment. Relapse was defined as occurrence of moderate or severe heartburn andlor acid regurgitation, andlor intake of antisecretory agents or prokinetics, andlor performance of an upper GI endoscopy during followup. Intent to treat analysis included all patients who took at least one dose of study drugs. Step-wise logistic regression was used to identify the following potential prognostic factors: age, gender, BMI, disease history, tobacco and coffee intake, heartburn and regurgitation severity, symptom