Sima Patel

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					Sima Patel 08/10/07

Treatment of Patients With Persistent Heartburn Symptoms: A Double-Blind, Randomized Trial Clinical Gastroenterology and Hepatology 2006; 4:50-56
Clinical Case: 45 year old female with a known diagnosis of gastroesophageal reflux disease who is currently taking a lansoprazole 30mg daily presents to clinic with continued complaints of heartburn and acid reflux. She has had a negative H.pylori test. Clinical Question: Should I increase the dosing of her lansoprazole to twice daily or switch her to another PPI.

STUDY DESIGN 10 week clinical trial 2 week baseline symptom assessment period (lansoprazole 30mg daily) lansoprazole 30mg BID 8 week treatment period Esomeprazole 40mg daily

Instructed to take study medication 30 min prior to breakfast and 30 min prior to dinner. Pre-screening daily symptom diary scoring 0 none Mild 1 symptoms easily tolerated and not lasting long Moderate 2 symptoms caused some discomfort but did not interfere with usual activities Severe 3 symptoms caused much discomfort and interfered with usual activities Eligibility  Age ≥18  h/o heartburn ≥ 2 days/wk on lansoprazole 30mg daily during 30 days preceding screening  log without missing ≥ 3 consecutive days  cumulative log score ≥ 4 Exclusion Criteria  current or history of esophageal ulcers/strictures  current or history of gastric ulcers  current or history of duodenal ulcers  gastric or esophageal pathology (judged to be clinically significant by investigator)  persistent heartburn symptoms for > 1 year on lansoprazole 30mg daily  serologic evidence of H.pylori  pregnancy  lactation  received one of the following drugs during 2 weeks prior: o theophylline o bismuth salts o warfarin o phenytoin o barbiturates o antineoplastic agents o erythromycin o clarithromycin o sucralfate Primary Clinical Outcome: Secondary Clinical Outcomes: % heartburn-free days from Day 8 to end of study % nighttime heartburn-free days, % epigastric pain-free days, % acid regurgitation free days


420 Patients Assessed for eligibility

328 eligible (randomized to study treatments)

92 failed screening

2 did not meet Inclusion criteria

2 unwilling to continue

88 other

160 Esomeprazole 40mg daily

168 lansoprazole 30mg BID

22 Analysis Exclusion

138 Analyzed

144 Analyzed

24 Analysis Exclusion

 Baseline GERD Characteristics (Table 2) o Lansoprazole group  49.1% reported moderate heartburn  36.8% reported mild acid regurgitation  32.6% reported mild epigastric pain o Esomeprazole group  47.1% reported moderate heartburn  39.1% reported mild acid regurgitation  39.1% reported mild epigastric pain % of heartburn free days o 54.4% for Esomeprazole 40mg daily o 57.7% for Lansoprazole 30mg PO BID % of patients ANY improvement in symptoms from baseline to end of treatment o Esomeprazole group  83.3% reported improvement in heartburn  76.8% reported improvement in acid regurgitation  67.4% reported improvement in epigastric pain o Lansoprazole group  83.3% reported improvement in heartburn  72.9% reported improvement in acid regurgitation  61.1% reported improvement in epigastric pain

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1. Is the standard of therapy effective? And does the experimental therapy have an advantage which is generalizable? Increasing the dose of lansoprazole to twice daily for persistent heartburn symptoms is generally an effective standard of therapy for persistent heartburn symptoms. It is also common clinical practice to switch to another PPI if a patient has persistent heartburn symptoms. In this study, the main hypothesis tested was that changing to esomeprazole once daily was at least as effective as using lansoprazole twice a day. The study does not show that one treatment is superior to the other, but rather that one is not inferior to the other. Factors that may be used to determine whether one therapy may have an advantage, given the conclusion that one treatment arm is at least as effective as the other treatment arm, could include secondary advantages such as cost or easier administration of medications. Was the assignment of patients to the treatments really randomized? Yes, the patients were assigned by computer generated program to the two treatment arms. Is it probable that the groups differ by less than a minimum effect? Can an acceptable minimum effect be defined in terms of the outcome measures? Yes, a difference of <10% between the lower limit of the confidence interval of the two treatment groups allowed for the conclusion that one treatment (esomeprazole 40mg daily) effect was at least as effective as the other treatment effect (lansoprazole 30mg BID). It is probable that the groups differ by less than a minimum effect; however this is based on the non-inferiority limit set by the study. Was the timeframe for followup sufficient to conclude that the therapies are equivalent? The timeframe for followup was 8 weeks. This time frame was sufficient to determine whether the two therapies were equivalent. Were factors which determined participation in the study identical to those for receiving the standard therapy? Yes, factors including heartburn and persistence of heartburn on once daily lansoprazole determined participation in the study. Were all patients who entered the study accounted for at its conclusion? Not really. The study did not provide information regarding specific reasons for exclusion of certain patients from the trial. There was also no true intention to treat. Were the treatments administered as they would be in practice? Yes, both esomeprazole and lansoprazole were administered as they would be in practice. Twice daily dosing of lansoprazole was administered 30 minutes before breakfast and 30 minutes before dinner as would normally be prescribed and administered. Once daily esomeprazole was also administered in usual practice.







Conclusion: This study accomplished the presented hypothesis (that switching from lansoprazole 30mg daily to esomeprazole 40mg daily was at least as effective as taking lansoprazole BID) however did not show superiority of using lansoprazole 30mg BID to esomeprazole 40mg daily or superiority of using esomeprazole daily to lansoprazole 30mg BID.

RESOURCES: 1. Krishhner, Bram. Methodological Standars for Assessing Therapeutic Equivalence. Journal of Clinical Epidemiology 1991; volume 44, No 8. 839-849.