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M1868 Esomeprazole for the Relief of Nighttime Heartburn in Patients with Gastroesophageal Reflux Disease (GERD)-Related Sleep Disturbances
last 3 months were recruited. Patients had to have erosive esophagitis on endoscopy or abnormal pH test. Baseline symptom severity and frequency were assessed during a 1-week run-in period using a daily symptom diary. Subsequently, patients underwent stimulus response functions to intraesophageal acid perfusion using a validated stressful stimulus. (Subjects were required to subvocally perform subtractions of numbers as rapidly as possible.) Thereafter, patients were randomized (2:1 ratio) to either placebo or esomeprazole 40 mg once daily for 8 weeks. One week prior to conclusion of the study, subjects were evaluated again for symptoms severity and frequency using a daily questionnaire. During the last day of therapy, subjects underwent stimulus response functions to intraesophageal acid perfusion using a similar stressor as baseline. Results: A total of 31 patients were randomized into the treatment arm (mean age 48.6 ± 2.8, M/F 21/10) and 16 into the placebo arm (mean age 52.3 ± 4.3, M/F 12/4). The antireflux group demonstrated a significant reduction in the score of daytime heartburn (15.5 ± 2.9 vs. 5.9 ± 2.8, P=0.01), nighttime heartburn (17.7 ± 3.7 vs. 4.2 ± 1.2, P<0.001), and regurgitation (8.6 ± 2.9 vs. 2.9 ± 1.1, P=0.04) on treatment. In contrast, the placebo group showed no significant difference in daytime heartburn (8.1 ± 1.8 vs. 8.7 ± 1.97, P=0.8), nighttime heartburn (9.9 ± 3.5 vs. 5.2 ± 1.5, P=0.3), and regurgitation (4.6 ± 1.8 vs. 3.5 ± 1.0, P=0.7) between baseline and treatment. In the antireflux group, there was a significant increase in lag time to symptom perception (187 ± 30 vs. 289.7 ± 38.7 seconds, P=0.04) and decrease in intensity rating (7.6 ± 0.7 vs. 5.0 ± 0.7, P= 0.02) as well as acid perfusion sensitivity score (35.7 ± 4.2 vs. 21.7 ± 3.8, P=0.02). There was no significant difference in any of the stimulus response functions to acid in the placebo group between baseline and treatment (206.7 ± 42.9 vs. 230.6 ± 50.96 seconds, P=0.7; 8.7 ± 1.4 vs. 8.5 ± 1.5, P=0.9; 41.45 ± 7.4 vs. 39.7 ± 7.7, P=0.9, respectively). Conclusion: This is the first study to show that antireflux treatment attenuates the effect of acute stress on perceptual responses to intraesophageal acid exposure. M1870 Resolution of Persistent GERD Symptoms After a Change in Therapy: EncomPASS - a Cluster-Randomized Study in Primary Care David Armstrong, Paul Moayyedi, Richard H. Hunt, Yao Lei, Margaret Bukoski, Robert J. White
M1868
Background: Many patients (pts) with GERD have persistent symptoms despite prescription therapy. A prior validation study of the proton pump inhibitor (PPI) Acid Suppression Symptom (PASS) test (a 5-item, Yes/No questionnaire) identified pts with persistent GERD symptoms, 32% of whom became symptom-free (Global Overall Symptom [GOS] score) 4 wks after switching from their current PPI therapy to esomeprazole (E) [1]. We evaluated whether a PASS test-based management strategy of changing GERD therapy would improve GERD symptoms compared with maintaining current therapy. Methods: In this multicenter, cluster-randomized, open-label study, Canadian primary care centers were randomized to intervention ‘I' or control ‘C' arms. After baseline assessment, pts with persistent GERD symptoms (ie, PASS test failure) continued current therapy ‘C' or switched to E 20 or 40mg daily (dosing at physician's discretion) ‘I' for 4 wks. The primary endpoint was the change in GOS score from baseline to 4 wks; secondary endpoints included freedom from symptoms (GOS, PASS test, RDQ-heartburn [RDQ-HB]). Analysis was carried out at the subject level in those with intention-to-treat (ITT) data for the primary and secondary endpoints with adjustment for variation attributable to center. Results: After center randomization, 973 pts (650 on prior PPIs) were recruited at 136 ‘I' centers and 591 (362 PPI) at 92 ‘C' centers; 938/973 (96.4%) ‘I' pts received E 40mg daily [data missing for 4 (0.4%)]. The difference in change in GOS scores from baseline to 4 wks between arms was -0.9 (95% CI: -1.1 to -0.6; p<.0001) for ITT pts and -0.8 (-1.1 to -0.6; p<.0001) for evaluable pts on PPIs at baseline. The odds ratio for symptom resolution (PASS) in ‘I' pts was 4.0 (95% CI: 2.7 to 6.0; p<.0001). Conclusions: After 4 wks, a change to E 20 or 40mg daily for persistent GERD symptoms identified by the PASS test was associated with a greater improvement in overall symptoms than continuing prior therapy (all or PPI). A greater proportion of pts became symptom free with ‘I' than with ‘C'. A PASS test-based management strategy to identify GERD pts with persistent symptoms in primary care and change therapy leads to symptom resolution in a substantial proportion of pts. Supported by AstraZeneca Canada Inc. [1] Armstrong D, et al. Can J Gastroenterol 2005;19:350-8 ITT analysis at 4 wks
Esomeprazole for the Relief of Nighttime Heartburn in Patients with Gastroesophageal Reflux Disease (GERD)-Related Sleep Disturbances David A. Johnson, Clara Hwang, Kurt A. Brown Aim: To determine the efficacy of esomeprazole on the relief of nighttime heartburn in patients with GERD. Methods: This 4-wk multicenter, randomized, double-blind, placebocontrolled study (D9612L00122; NCT00660660) was conducted in the United States and included patients aged 18-85 y with GERD who had a history of erosive esophagitis or episodes of heartburn or acid regurgitation for ≥3 mo, a history of GERD-related sleep disturbances (trouble falling asleep, frequent awakenings, overall poor sleep quality) for ≥1 mo, and nighttime GERD symptoms averaging ≥2 episodes in a 7-d period before enrollment. Patients with GERD-related sleep disturbances and moderate or severe nighttime heartburn on ≥3 of the last 7 nights of the 1-2-wk run-in period were randomized to esomeprazole 20 mg taken before breakfast or placebo for 4 wk. Patients with conditions other than GERD known to affect sleep were excluded. Sleep medication was allowed if usage was stable (≥3 mo) and was expected to remain stable throughout the study. Nighttime heartburn symptom frequency and severity (none, mild, moderate, severe) were assessed using a daily diary card. The primary end point, relief of nighttime heartburn, was defined as a daily diary card response of none on ≥6 d and at most mild on 1 d during the last 7 d of the study. Relief of GERD-related sleep disturbance was defined as a yes response to the question “Did you have trouble sleeping last night due to your heartburn or other symptoms of GERD?” on ≤2 of the last 7 consecutive days in the study. Complete resolution of sleep disturbance was defined as 7 consecutive days of no trouble sleeping the previous night. Differences in relief rates between the treatment groups were assessed using a Chi-square test. Results: During the last 7 d of the study, relief of nighttime heartburn and sleep disturbance was significantly greater in the esomeprazole treatment group compared with placebo (P<.01; Table). Median days to first complete resolution of sleep disturbance (first of 7 consecutive days with severity of none to sleep disturbance) was 9 d for patients who received esomeprazole, whereas the majority of patients (>50%) who received placebo never experienced complete resolution (P=.0001). Conclusion: Esomeprazole 20 mg once daily is effective for the relief of GERD-related moderate to severe nighttime heartburn and GERD-related sleep disturbances. Supported by AstraZeneca LP Relief of Nighttime Heartburn and GERD-Related Sleep Disturbance After 4 Weeks
*P < .01 vs. placebo. M1871 M1869
Proton Pump Inhibitors: Are We Wasting Money and Ignoring the Risk? Alex J. Kent, Bethan Graf, Marcus Harbord
The Effect of Antireflux Versus Placebo On Perception of Intraesophageal Acid in Patients with Gastroesophageal Reflux Disease (GERD) Undergoing a Mental Arithmetic Stressor Test—a Randomized, Double-Blind, PlaceboControlled, Parallel Trial Choo Hean Poh, Anita Gasiorowska, Tomas Navarro-Rodriguez, Marcia R. Willis, North J. Noelck, Ronnie Fass
INTRODUCTION: The UK National Health Service spends over $450 million annually on proton pump inhibitors (PPI). The National Institute for Clinical Excellence advise that patients with dyspepsia/GORD should receive a PPI for 1-2 months and if symptoms recur it should be prescribed at the lowest dose. £50 million could be saved annually if their guidelines were followed more strictly. There is growing concern regarding complications associated with PPI use, including increased risk of enteric infections (specifically Clostridium difficile infection), community-acquired pneumonia, hip fractures and disturbed calcium homeostasis. AIMS & METHODS: We aimed to assess the degree of inappropriate PPI prescription and potential associated complications. We prospectively reviewed 300 medical patients admitted through Chelsea and Westminster Hospital. Information gathered included: patient demographics, comorbidities, BMI, smoking/ETOH history, medications, indication
Background: Acute stress can exacerbate heartburn in GERD patients by enhancing perceptual responses to intraesophageal acid exposure. Thus far, it is unknown if antireflux treatment can attenuate this effect of acute stress. Aim: To determine if antireflux treatment can attenuate the effect of acute stress on perception of intraesophageal acid exposure as compared to placebo. Method: GERD patients with at least 2 episodes of heartburn per week for the
A-435
AGA Abstracts
AGA Abstracts
were analysed by blinded observation. Treatment effect was determined by Kruskall Wallis test and comparison to placebo by Wilcoxon Rank Sum test. Results. In the placebo group reflux episodes increased from D-1 to D6. This effect was reduced in the ADX10059 treatment groups. A significant treatment effect was seen for total acid exposure % (p=0.048) and number of weakly acidic reflux episodes (p = 0.0411). Significant differences from placebo were seen for 125mg b.i.d for various reflux measures. Trends were also seen for the 250mg b.i.d. dose which did not appear more effective than 125mg b.i.d. The 50mg b.i.d dose was not significantly superior to placebo. Twice daily administration of ADX10059 gave satisfactory 24 hour plasma concentrations. All 3 doses were well tolerated. Adverse event frequency was 50 mg : n=3 ; 125 mg : n=8 ; 250 mg : n=9. All were mild or moderate. The most common were insomnia (n=4), constipation (n=2) and flatulence (n=2). Conclusion. Compared to placebo, ADX10059 dose dependently decreased gastro-esophageal reflux events in healthy subjects. The tolerability of the MR formulation is suitable for longer term treatment to evaluate clinical symptom control in GERD patients. Median and 95% CI of changes Day -1 to Day 6 for 5 hour pH-impedance monitoring period
M1868
Background: Many patients (pts) with GERD have persistent symptoms despite prescription therapy. A prior validation study of the proton pump inhibitor (PPI) Acid Suppression Symptom (PASS) test (a 5-item, Yes/No questionnaire) identified pts with persistent GERD symptoms, 32% of whom became symptom-free (Global Overall Symptom [GOS] score) 4 wks after switching from their current PPI therapy to esomeprazole (E) [1]. We evaluated whether a PASS test-based management strategy of changing GERD therapy would improve GERD symptoms compared with maintaining current therapy. Methods: In this multicenter, cluster-randomized, open-label study, Canadian primary care centers were randomized to intervention ‘I' or control ‘C' arms. After baseline assessment, pts with persistent GERD symptoms (ie, PASS test failure) continued current therapy ‘C' or switched to E 20 or 40mg daily (dosing at physician's discretion) ‘I' for 4 wks. The primary endpoint was the change in GOS score from baseline to 4 wks; secondary endpoints included freedom from symptoms (GOS, PASS test, RDQ-heartburn [RDQ-HB]). Analysis was carried out at the subject level in those with intention-to-treat (ITT) data for the primary and secondary endpoints with adjustment for variation attributable to center. Results: After center randomization, 973 pts (650 on prior PPIs) were recruited at 136 ‘I' centers and 591 (362 PPI) at 92 ‘C' centers; 938/973 (96.4%) ‘I' pts received E 40mg daily [data missing for 4 (0.4%)]. The difference in change in GOS scores from baseline to 4 wks between arms was -0.9 (95% CI: -1.1 to -0.6; p<.0001) for ITT pts and -0.8 (-1.1 to -0.6; p<.0001) for evaluable pts on PPIs at baseline. The odds ratio for symptom resolution (PASS) in ‘I' pts was 4.0 (95% CI: 2.7 to 6.0; p<.0001). Conclusions: After 4 wks, a change to E 20 or 40mg daily for persistent GERD symptoms identified by the PASS test was associated with a greater improvement in overall symptoms than continuing prior therapy (all or PPI). A greater proportion of pts became symptom free with ‘I' than with ‘C'. A PASS test-based management strategy to identify GERD pts with persistent symptoms in primary care and change therapy leads to symptom resolution in a substantial proportion of pts. Supported by AstraZeneca Canada Inc. [1] Armstrong D, et al. Can J Gastroenterol 2005;19:350-8 ITT analysis at 4 wks
Esomeprazole for the Relief of Nighttime Heartburn in Patients with Gastroesophageal Reflux Disease (GERD)-Related Sleep Disturbances David A. Johnson, Clara Hwang, Kurt A. Brown Aim: To determine the efficacy of esomeprazole on the relief of nighttime heartburn in patients with GERD. Methods: This 4-wk multicenter, randomized, double-blind, placebocontrolled study (D9612L00122; NCT00660660) was conducted in the United States and included patients aged 18-85 y with GERD who had a history of erosive esophagitis or episodes of heartburn or acid regurgitation for ≥3 mo, a history of GERD-related sleep disturbances (trouble falling asleep, frequent awakenings, overall poor sleep quality) for ≥1 mo, and nighttime GERD symptoms averaging ≥2 episodes in a 7-d period before enrollment. Patients with GERD-related sleep disturbances and moderate or severe nighttime heartburn on ≥3 of the last 7 nights of the 1-2-wk run-in period were randomized to esomeprazole 20 mg taken before breakfast or placebo for 4 wk. Patients with conditions other than GERD known to affect sleep were excluded. Sleep medication was allowed if usage was stable (≥3 mo) and was expected to remain stable throughout the study. Nighttime heartburn symptom frequency and severity (none, mild, moderate, severe) were assessed using a daily diary card. The primary end point, relief of nighttime heartburn, was defined as a daily diary card response of none on ≥6 d and at most mild on 1 d during the last 7 d of the study. Relief of GERD-related sleep disturbance was defined as a yes response to the question “Did you have trouble sleeping last night due to your heartburn or other symptoms of GERD?” on ≤2 of the last 7 consecutive days in the study. Complete resolution of sleep disturbance was defined as 7 consecutive days of no trouble sleeping the previous night. Differences in relief rates between the treatment groups were assessed using a Chi-square test. Results: During the last 7 d of the study, relief of nighttime heartburn and sleep disturbance was significantly greater in the esomeprazole treatment group compared with placebo (P<.01; Table). Median days to first complete resolution of sleep disturbance (first of 7 consecutive days with severity of none to sleep disturbance) was 9 d for patients who received esomeprazole, whereas the majority of patients (>50%) who received placebo never experienced complete resolution (P=.0001). Conclusion: Esomeprazole 20 mg once daily is effective for the relief of GERD-related moderate to severe nighttime heartburn and GERD-related sleep disturbances. Supported by AstraZeneca LP Relief of Nighttime Heartburn and GERD-Related Sleep Disturbance After 4 Weeks
*P < .01 vs. placebo. M1871 M1869
Proton Pump Inhibitors: Are We Wasting Money and Ignoring the Risk? Alex J. Kent, Bethan Graf, Marcus Harbord
The Effect of Antireflux Versus Placebo On Perception of Intraesophageal Acid in Patients with Gastroesophageal Reflux Disease (GERD) Undergoing a Mental Arithmetic Stressor Test—a Randomized, Double-Blind, PlaceboControlled, Parallel Trial Choo Hean Poh, Anita Gasiorowska, Tomas Navarro-Rodriguez, Marcia R. Willis, North J. Noelck, Ronnie Fass
INTRODUCTION: The UK National Health Service spends over $450 million annually on proton pump inhibitors (PPI). The National Institute for Clinical Excellence advise that patients with dyspepsia/GORD should receive a PPI for 1-2 months and if symptoms recur it should be prescribed at the lowest dose. £50 million could be saved annually if their guidelines were followed more strictly. There is growing concern regarding complications associated with PPI use, including increased risk of enteric infections (specifically Clostridium difficile infection), community-acquired pneumonia, hip fractures and disturbed calcium homeostasis. AIMS & METHODS: We aimed to assess the degree of inappropriate PPI prescription and potential associated complications. We prospectively reviewed 300 medical patients admitted through Chelsea and Westminster Hospital. Information gathered included: patient demographics, comorbidities, BMI, smoking/ETOH history, medications, indication
Background: Acute stress can exacerbate heartburn in GERD patients by enhancing perceptual responses to intraesophageal acid exposure. Thus far, it is unknown if antireflux treatment can attenuate this effect of acute stress. Aim: To determine if antireflux treatment can attenuate the effect of acute stress on perception of intraesophageal acid exposure as compared to placebo. Method: GERD patients with at least 2 episodes of heartburn per week for the
A-435
AGA Abstracts
AGA Abstracts
were analysed by blinded observation. Treatment effect was determined by Kruskall Wallis test and comparison to placebo by Wilcoxon Rank Sum test. Results. In the placebo group reflux episodes increased from D-1 to D6. This effect was reduced in the ADX10059 treatment groups. A significant treatment effect was seen for total acid exposure % (p=0.048) and number of weakly acidic reflux episodes (p = 0.0411). Significant differences from placebo were seen for 125mg b.i.d for various reflux measures. Trends were also seen for the 250mg b.i.d. dose which did not appear more effective than 125mg b.i.d. The 50mg b.i.d dose was not significantly superior to placebo. Twice daily administration of ADX10059 gave satisfactory 24 hour plasma concentrations. All 3 doses were well tolerated. Adverse event frequency was 50 mg : n=3 ; 125 mg : n=8 ; 250 mg : n=9. All were mild or moderate. The most common were insomnia (n=4), constipation (n=2) and flatulence (n=2). Conclusion. Compared to placebo, ADX10059 dose dependently decreased gastro-esophageal reflux events in healthy subjects. The tolerability of the MR formulation is suitable for longer term treatment to evaluate clinical symptom control in GERD patients. Median and 95% CI of changes Day -1 to Day 6 for 5 hour pH-impedance monitoring period