Lansoprazole Compared With Ranitidine
for the Treatment of Nonerosive
Gastroesophageal Reflux Disease

Joel E. Richter, MD; Donald R. Campbell, MD; Peter J. Kahrilas, MD; Bidan Huang, PhD; Cheryl Fludas, MS Background: Traditionally, proton pump inhibitors are
percentages of days and nights with heartburn, less used primarily for patients with esophagitis. However, pain severity of both day and night heartburn, fewer patients with nonerosive reflux disease may also benefit days of antacid use, and smaller amounts of antacid use compared with patients who were treated withranitidine or placebo. The incidence of possible or Objective: To compare the safety and symptom relief
probable treatment-related adverse reactions was com- efficacy of lansoprazole with ranitidine therapy and parable among the treatment groups; abdominal pain and diarrhea were the most commonly reportedadverse events. No statistically significant differences Methods: In 2 randomized, double-blind, multicenter
were noted between treatment groups in laboratory trials of 901 patients with symptomatic reflux disease, which was confirmed by endoscopy to be nonerosive, re-ceived lansoprazole, 15 or 30 mg once daily; ranitidine, Conclusion: Lansoprazole therapy is more effective than
150 mg twice daily; or placebo for 8 weeks.
standard dosages of ranitidine or placebo in relievingsymptoms in patients with endoscopically confirmed non- Results: Analysis of daily diary data during the first 4
weeks and for the entire 8 weeks of treatment revealedthat patients who were treated with either dosageof lansoprazole reported significantly (PϽ.05) lower Arch Intern Med. 2000;160:1803-1809 GASTROESOPHAGEALre- haveamoreprofoundimpactonpatient
quality of life than duodenal ulcers, un- treated hypertension, mild congestive heart patient functioning and quality of life and damage. While a large percentage of indi- manifestations. These can range from mild ation; severe cases may involve stricture or hemorrhage.5,6 Unfortunately, from a di- agnostician’s viewpoint, with regard to negative impact on patients’ physical and from those with more severe forms.7 There- See also page 1810
esophageal mucosal exposure to the acidic gastric contents is the basis for reducing an acute or transient event, but rather a ent, the esophagitis needs to be healed.
in severity and/or frequency. A recent study (Dr Kahrilas); AbbottLaboratories, Abbott Park, Ill when present, heal esophagitis.8-14 Proton polled 7 years later.3 These symptoms can (REPRINTED) ARCH INTERN MED/ VOL 160, JUNE 26, 2000 2000 American Medical Association. All rights reserved.
inflammatory drugs, corticosteroid therapy (the equiva- AND METHODS
lent of Ͼ10 mg of prednisone per day), or aspirin (Ͼ325mg per day); use of an H2RA, anticholinergic, and/orprokinetic agent during the pretreatment period; use of a STUDY DESIGN
proton pump inhibitor during the pretreatment period; oruse of any investigational drug within 12 weeks prior to Two phase III, multicenter (37 investigative sites in each trial), initiating study treatment. Female subjects of childbear- randomized, active-controlled, double-blind, parallel-group ing potential agreed to continued use of an appropriate studies compared the safety and efficacy of 8 weeks of lan- means of contraception, were nonlactating, and had a nega- soprazole therapy, 15 mg once daily, and lansoprazole therapy, tive serum pregnancy test result. Eligible subjects were not 30 mg once daily, with the efficacy of ranitidine therapy, 150 to have received any blood products within 12 weeks of mg twice daily, in patients with endoscopically confirmed, initiating the study. Approval for the study was obtained symptomatic, nonerosive (grade 0 or 1 esophagitis) reflux dis- from the human studies committee at each participating ease. The study procedures and designs were identical ex- investigative site. Written informed consent was obtained cept for the inclusion of a placebo group in one of the two prior to each patient’s enrollment into the study.
studies. Antacid tablets (Gelusil [9.7 mmol of acid neutral-izing capacity per tablet]; Parke-Davis, Morris Plains, NJ) were TREATMENT RANDOMIZATION
also supplied to each patient to be taken on an as-needed ba-sis for the relief of reflux symptoms.
Patients meeting the inclusion criteria in the comparativetrial including placebo were randomized in a 2:2:2:1 ratio PATIENT SELECTION
to 1 of the 4 treatment groups (lansoprazole, 15 mg oncedaily; lansoprazole, 30 mg once daily; ranitidine, 150 mg Study randomization occurred after a 7- to 10-day pretreat- twice daily; or placebo). Patients enrolled in the second com- ment period, during which patients recorded the fre- parative study were randomized in a 1:1:1 ratio to 1 of the quency and severity of day and night heartburn. Patients 3 treatment groups (lansoprazole, 15 mg once daily; lan- who recorded moderate to severe day and/or night heart- soprazole, 30 mg once daily; or ranitidine, 150 mg twice burn for at least 50% of the days during the pretreatment daily). Lansoprazole, ranitidine, and placebo were sup- period and reported moderate to severe day and/or night plied to patients as identical gray, opaque capsules. Pa- heartburn for more than 50% of the days over the past tients were instructed to self-administer one capsule prior 6 months prior to study entry were considered eligible for study inclusion. At the baseline visit, patients wererequired to have endoscopically proven nonerosive reflux PRETREATMENT AND STUDY EVALUATIONS
disease of grade 0 or 1 esophagitis (grade 0 was defined asnormal mucosa and grade 1 was defined as mucosal edema, Pretreatment Evaluations
hyperemia, and/or friability of mucosa).
Patients were excluded from study participation if During the pretreatment period (7-10 days prior to study they had any of the following: Barrett esophagus; duodenal day 1), patients completed daily diaries to determine eli- and/or gastric ulcer 3 mm in diameter or larger; esopha- gibility, reported a complete medical history, and under- geal stricture requiring dilation; coexisting systemic dis- went a complete physical examination, including vital sign ease affecting the esophagus (eg, scleroderma); history of gastrointestinal bleeding or gastric, duodenal, or esopha-geal surgery; clinically significant diseases involving major Study Evaluations
organs; clinically significant abnormal laboratory values;evidence of current alcohol abuse or illegal drug use; long- Endoscopy was performed in all patients at study day 1 prior term use of ulcerogenic drugs, including nonsteroidal anti- to dosing to document the absence of erosive (grade 2 or tom relief and healing earlier and more effectively than ei- ther standard or high-dose H2RA therapy.10 The superiorefficacy of proton pump inhibitor therapy compared STUDY POPULATION
with H2RA therapy may be the result of the differences inthe mechanism of action (H2RAs do not block meal- A total of 925 patients were enrolled in the 2 studies: lan- stimulated acid secretion) as well as the potential for the soprazole, 15 mg once daily (n = 284); lansoprazole, 30 development of tolerance of H2RAs.11,15,16 mg once daily (n = 288); ranitidine, 150 mg twice daily Clinical studies have demonstrated that proton pump (n = 283); and placebo (n = 70). Patients with esophagi- inhibitors are more effective than H2RAs in the treat- tis (grade Ͼ1) or Barrett esophagus at baseline were ex- ment of severe reflux disease.10 However, most patients cluded from the intent-to-treat analysis. In addition, pa- with GERD have milder nonerosive forms of the dis- tients were not included in the intent-to-treat analysis if ease. Our studies were designed to measure the safety and no diary data were recorded during the treatment pe- effectiveness of a proton pump inhibitor (lansoprazole; riod. Eight hundred ninety-eight patients were in- Takeda Abbott Pharmaceuticals, Deerfield, Ill) vs an H2RA cluded in the intent-to-treat patient efficacy analysis.
(ranitidine; Glaxo Wellcome, Research Triangle Park, NC) Among these patients, the 3 active treatment groups (ie, or placebo in milder (nonerosive) forms of GERD.
lansoprazole, 15 mg; lansoprazole, 30 mg; and raniti- (REPRINTED) ARCH INTERN MED/ VOL 160, JUNE 26, 2000 2000 American Medical Association. All rights reserved.
higher) esophagitis. Three gastric biopsy specimens were capsules were counted to assess compliance with the pre- obtained at the time of endoscopy to assess Helicobacter py- lori status. Endoscopy also documented the presence or ab-sence of duodenal and/or gastric ulcer(s). At the study day STATISTICAL ANALYSIS
1 visit, qualifying patients were randomized to a treat-ment group, dispensed study medication and Gelusil, and Baseline demographic data, clinical characteristics, and gas- trointestinal history were compared among the treatment In the daily treatment diary, patients were instructed groups using ␹2 tests for categorical variables and a one- to document day and night heartburn (graded as none, mild, way analysis of variance for continuous variables. Height moderate, or severe), as well as frequency of Gelusil use and body weight were analyzed separately for men and and self-administration of study medication.
Patients returned after 4 and 8 weeks of treatment. Daily The primary efficacy variables were the assessments diaries were also collected and reviewed at these visits.
of daytime and nighttime heartburn and antacid usageas recorded in the patient diaries. The Wilcoxon 2- SAFETY AND COMPLIANCE EVALUATIONS
sample test was used for treatment group comparisons ofthe mean severity of day and night heartburn, the per- centage of days and nights with heartburn, and the per-centage of days and amount of antacid usage. In addi- Safety of the treatment was monitored by complete physi- tion, treatment group comparisons of the average daily cal examination, adverse event assessments, vital sign de- severity and percentage of days with day heartburn and terminations (including blood pressure after 3 minutes in night heartburn during the entire 8-week treatment the sitting position, pulse rate after at least 30 seconds, res- period were performed, controlling for baseline heart- piratory rate, temperature, and body weight), and routine burn severity, H pylori status during the pretreatment laboratory evaluations (including hematologic testing, period, investigator, and demographic characteristics serum chemistry testing, urinalysis, pregnancy testing in using the van Elteren method of combining Wilcoxon women, and theophylline and digoxin level determina- test results from independent strata.17 Heartburn severity tions in patients taking these medications). Patients were of none, mild, moderate, and severe was scored as 0, 1, required to have fasted for at least 8 hours prior to blood 2, and 3, respectively. Additionally, a multiple linear sampling for laboratory analyses. The clinical laboratory regression analysis of daytime and nighttime heartburn tests were analyzed at a central laboratory (Covance Cen- was performed to identify factors that might significantly tral Laboratory Services, Indianapolis, Ind).
influence symptom relief. The factors included in the Investigators recorded their opinion of every adverse model were treatment, baseline heartburn severity, H event reported as having a probable or possible relation- pylori status at baseline, age, sex, race, and lifestyle con- ship or no relationship to the study drug. Assigning a prob- siderations (alcohol use, caffeine use, and tobacco use).
able relationship to a study drug meant that, in the inves- Results from the intent-to-treat analyses for efficacy are tigator’s opinion, the adverse event had a timely relationship to study drug administration and no alternative cause of The proportions of patients reporting adverse the adverse event was apparent. A possible relationship to events were compared between treatment groups using a study drug meant that, in the investigator’s opinion, a po- the Fisher exact test. Treatment group comparisons of tential alternative cause of the adverse event existed.
the mean change of laboratory values and vital signsfrom baseline to the final treatment visit were based on Compliance
contrasts within the one-way analysis of variance withtreatment groups as the factor. Treatment group com- All patients were requested to bring their remaining drug parisons for efficacy and safety were made between each supplies to the week-4 and week-8 visits. All remaining dosage of lansoprazole and ranitidine or placebo.
dine, 150 mg) were comparable at baseline with respect A total of 98 enrolled patients prematurely withdrew to age; sex; race; tobacco, alcohol, and caffeine use; and from the study. The occurrence of premature discontinu- H pylori status (Table 1). Male and female patients in
ations among active treatment groups was similar: 29 (10%) each treatment group were also comparable with regard of 284 patients receiving lansoprazole, 15 mg once daily; 26 (9%) of 288 patients receiving lansoprazole, 30 mg once Patients randomized to receive treatment with either daily; 28 (10%) of 283 patients receiving ranitidine, 150 dosage of lansoprazole, ranitidine, or placebo were com- mg twice daily; and 15 (21%) of 70 patients receiving pla- parable at baseline for frequency and severity of day or night cebo. The most common reasons for premature discon- heartburn and frequency of antacid use (Table 2). Pa-
tinuation included adverse events (8 patients from the lan- tients randomized to receive placebo and lansoprazole, 30 soprazole, 15 mg once daily, group; 8 from the lansoprazole, mg, reported a higher mean number of antacid tablets taken 30 mg once daily, group; 10 from the ranitidine, 150 mg per day compared with those randomized to receive lan- twice daily, group; and 6 from the placebo group) and thera- soprazole, 15 mg. Patients randomized to receive lanso- peutic failure (5 patients from the lansoprazole, 15 mg once prazole, 30 mg, reported a significantly lower average day- daily, group; 2 from the lansoprazole, 30 mg once daily, time heartburn severity at baseline compared with those group; 5 from the ranitidine, 150 mg twice daily, group; randomized to receive placebo (P = .04).
(REPRINTED) ARCH INTERN MED/ VOL 160, JUNE 26, 2000 2000 American Medical Association. All rights reserved.
Table 1. Baseline Characteristics of the Intent-to-Treat Population
No. of Patients (%)
150 mg Twice Daily
15 mg Once Daily
30 mg Once Daily
*From F test.
†From ␹2 test.
‡Includes ex-tobacco users.
§Includes ex-alcohol drinkers.
Table 2. Summary of Median Diary Data at Baseline
150 mg Twice Daily
15 mg Once Daily
30 mg Once Daily
*Statistically significant ( PՅ.05) vs placebo. Pain severity (range, 0-3) was scored as 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
tablets used per day compared with patients treated withranitidine.
Patients in the lansoprazole, 15 mg, treatment group re- No statistically significant differences in the corded significantly (PϽ.001) fewer days and nights with percentage of days or nights with heartburn, the aver- heartburn, less severe daytime and nighttime heart- age severity of daytime or nighttime heartburn pain, the burn, fewer days of antacid use, and fewer antacid tab- percentage of days that antacids were used, or the num- lets used per day during the first 4 weeks of treatment ber of tablets taken per day were observed between the and during the entire 8-week treatment period com- lansoprazole, 15 mg once daily, and lansoprazole, 30 pared with patients in the ranitidine group (Table 3).
mg once daily, treatment groups during the first 4 During the first 4 weeks of treatment and the entire 8-week weeks of the study or during the entire 8-week treat- treatment period, patients treated with lansoprazole, 30 mg, recorded significantly (PՅ.04) fewer days and nights Thirty-seven percent of patients treated with lan- with heartburn, less severe daytime and nighttime heart- soprazole, 15 mg, and 35% of those treated with lanso- burn, fewer days of antacid use, and fewer antacid prazole, 30 mg, were symptom-free for at least 80% of (REPRINTED) ARCH INTERN MED/ VOL 160, JUNE 26, 2000 2000 American Medical Association. All rights reserved.
Table 3. Summary of Median Diary Data at Weeks 0-4 and 0-8*
Ranitidine, 150 mg
Lansoprazole, 15 mg
Lansoprazole, 30 mg
Twice Daily (n = 278)
Once Daily (n = 276)
Once Daily (n = 277)
Weeks 0-4
Weeks 0-8
Weeks 0-4
Weeks 0-8
Weeks 0-4
Weeks 0-8
*Weeks 0-4 indicates the first 4 weeks of treatment; weeks 0-8, the entire 8 weeks of treatment.
†Statistically significant at PՅ.001 vs ranitidine therapy.
‡Statistically significant at PՅ.01 vs ranitidine therapy.
§Pain severity (range, 0-3) was scored as 0 = none, 1 = mild, 2 = moderate, and 3 = severe.
࿣Statistically significant at PՅ.05 vs ranitidine therapy.
their treatment days compared with 23% of patients mg (median, 21.4% and 19.6% of days, respectively) (PՅ.01). At weeks 4 and 8, patients treated with raniti- Patients treated with either dosage of lansoprazole dine reported significantly (PՅ.04) higher numbers of reported significantly lower average daytime and night- antacid tablets used per day (median, 0.82 and 0.78, re- time heartburn severity compared with those receiving spectively) compared with patients treated with lanso- ranitidine or placebo. During the first 4 weeks, the me- prazole, 15 mg (median, 0.46 and 0.43, respectively), and dian of the average daytime heartburn severity score was lansoprazole, 30 mg (median, 0.59 and 0.45, respectively).
0.64 for patients treated with ranitidine vs 0.36 for pa- The frequency of antacid use is associated with the tients treated with lansoprazole, 15 mg once daily, and frequency of days or nights with heartburn across all treat- 0.39 for patients treated with lansoprazole, 30 mg once ment groups. Between 86% and 98% of days of Gelusil daily (PՅ.002). During the entire 8-week treatment pe- use coincided with the presence of heartburn symptoms riod, the median of the average daytime heartburn se- across all treatment groups, with a higher percentage oc- verity score for patients treated with ranitidine was 0.53, curring in the placebo group and similar percentages oc- which was significantly (PՅ.001) higher than the scores curring among the active treatment groups.
for those treated with lansoprazole, 15 mg (0.32), and When comparisons were made with the placebo lansoprazole, 30 mg, (0.31). The median of the average group, patients treated with lansoprazole, 15 or 30 mg nighttime heartburn severity score at 4 weeks was 0.46 once daily, also reported both significantly lower per- for patients treated with ranitidine vs 0.25 and 0.29 for centages of days and nights with heartburn and signifi- patients treated with lansoprazole, 15 and 30 mg, respec- cantly lower severity scores for both daytime and night- tively (PՅ.006). These findings were similar to those dur- time heartburn, as well as less antacid usage.
ing the 8-week treatment period: patients treated with Daily diary data analyses, controlling for indi- ranitidine reported an average nighttime heartburn se- vidual influential factors, such as baseline heartburn se- verity of 0.36 vs 0.21 and 0.28 for patients treated with verity, baseline H pylori status, age, sex, race, and to- lansoprazole, 15 and 30 mg, respectively (PՅ.006).
bacco, alcohol, and caffeine consumption, and their effect Patients treated with ranitidine reported a signifi- on active treatment group differences, were comparable cantly higher percentage of days that they ingested ant- with overall diary results. Treatment with either dosage acids and a significantly higher average number of ant- of lansoprazole was associated with significant (PՅ.05) acid tablets ingested per day compared with those who decreases in heartburn frequency and severity com- received either dosage of lansoprazole. After 4 and 8 weeks pared with ranitidine treatment, 150 mg twice daily, or of treatment, patients treated with raniditine reported sig- nificantly higher percentages of days (median, 32.1% and Multiple linear regression analysis of diary data for 28.5% of days, respectively) using antacids than pa- factors (ie, treatment, baseline heartburn severity, H py- tients treated with lansoprazole, 15 mg (median, 17.9% lori status, age, race, and lifestyle) that might signifi- and 16.7% of days, respectively), and lansoprazole, 30 cantly influence symptom relief revealed that patients with (REPRINTED) ARCH INTERN MED/ VOL 160, JUNE 26, 2000 2000 American Medical Association. All rights reserved.
severe heartburn at baseline and patients who were non- individuals seeking symptom relief with over-the- drinkers tended to report more frequent and more se- counter antacid preparations and, more recently, with vere heartburn during the 8-week treatment period com- over-the-counter H2RAs. However, studies have found pared with those with moderate heartburn at baseline and that these over-the-counter formulations of H2RAs pro- patients who were drinkers, respectively. Diary analy- vide at best partial relief, with complete relief occurring ses revealed that lansoprazole therapy, 15 and 30 mg, was superior to ranitidine therapy in relieving day and night The widespread availability and direct-to-consumer heartburn when controlling for both baseline heartburn advertising of over-the-counter antireflux agents have sig- nificantly altered the traditional “step up” GERD treat-ment protocol. A substantial proportion of patients with reflux who currently present for medical consultation havealready tried and failed the traditional “first steps” of GERD The incidence of possible or probable treatment-related management (ie, antacid preparations, H2RAs).20,21 While adverse reactions was comparable among the treatment it is likely that these patients have not progressed to com- groups: 14% (41/284) in the lansoprazole therapy, 15 mg plications, such as erosions or stricture, their failure to once daily, group; 17% (50/288) in the lansoprazole respond to H2RA therapy suggests that they require more therapy, 30 mg once daily, group; 17% (49/283) in the ranitidine therapy, 150 mg twice daily, group; and 13% Several studies, including meta-analyses, have con- (9/70) in the placebo group experienced an event that firmed that proton pump inhibitor therapy is more ef- was considered to be possibly or probably treatment re- fective in raising and maintaining intragastric pH levels lated. Three severe adverse events (hematemesis, ab- above 4 for longer durations compared with H2RA dominal pain, and headache, 1 each in the ranitidine, 150 therapy.10,11,22-27 In a study by Bell and colleagues,22 treat- mg twice daily, lansoprazole, 15 mg once daily, and lan- ment with a proton pump inhibitor maintained intra- soprazole, 30 mg once daily, treatment groups, respec- gastric pH above 4.00 for between 15 and 21 hours a day tively) were considered to be possibly treatment re- compared with approximately 8 hours daily with treat- lated. Abdominal pain and diarrhea were the most commonly reported treatment-related adverse events. The By virtue of its potent and long-lasting effects on 24- majority of all treatment-emergent adverse events were hour intragastric pH and its ability to maintain pH above mild to moderate in severity among all treatment groups.
4.00 for extended periods, proton pump inhibitor therapy No clinically significant differences were noted between effectively relieves the symptoms of reflux even in cases treatment groups in the analysis of laboratory, physical of mild disease.7,18 Similar to the findings of this study, other investigators have also found that the percentagesof patients who experienced relief of their symptoms, in- cluding pain, are higher among those treated with a pro-ton pump inhibitor compared with those treated with an The results of these 2 large, multicenter, US studies in- dicate that once-daily treatment with a proton pump in- Controlling reflux symptoms not only improves a hibitor (lansoprazole at a dosage of either 15 or 30 mg) patient’s quality of life but may influence the develop- is significantly more effective than twice-daily adminis- ment of gastroesophageal adenocarcinoma. According to tration of ranitidine in controlling the incidence of day- a recent epidemiologic study, the more frequent, more se- time and nighttime heartburn. In addition, treatment with vere, and longer lasting the symptoms of gastroesopha- lansoprazole, 15 or 30 mg, significantly decreased the se- geal reflux, the greater the risk of developing gastroesopha- verity of daytime and nighttime heartburn compared with geal adenocarcinoma.28 Compared with those without treatment with ranitidine or placebo. Not surprisingly, reflux symptoms, individuals with recurrent reflux symp- patients treated with ranitidine and placebo consumed toms had an odds ratio of 7.7 (95% confidence interval, higher amounts of antacids on more days than patients 5.2-11.4) for developing gastroesophageal adenocarci- treated with either dosage of lansoprazole. Of interest, noma. This odds ratio increased to 43.5 (95% confidence when we controlled for other factors, such as H pylori interval, 18.3-103.5) among individuals with long- status and baseline heartburn severity, that may affect standing and severe symptoms of reflux.
symptom response, significantly higher percentages of In addition to providing greater symptomatic re- patients treated with lansoprazole reported daytime and lief, it has been suggested that the empiric use of proton nighttime heartburn relief and reduced symptom sever- pump inhibitors is a cost-effective approach to the man- ity compared with those treated with ranitidine. While agement of these patients.29,30 While it is not surprising the results observed in this study are consistent with that empiric treatment of patients with GERD using a prior studies comparing proton pump inhibitor therapy proton pump inhibitor is more cost-effective than with H2RA therapy in patients with milder forms of endoscopy, recent findings suggest that the use of a reflux disease,9,18,19 one limitation to this study may be proton pump inhibitor is only marginally more costly the rate (approximately 10%) of premature patient than the use of an H2RA, while being significantly more withdrawals, which may have resulted in patient selec- effective at relieving symptoms,31 maintaining symp- tomatic remission in those with mild reflux,32 and Gastroesophageal reflux disease affects a substan- improving quality of life.29 In a study of 685 patients tial proportion of the adult population,2 with many of these with suspected GERD who were randomized to receive (REPRINTED) ARCH INTERN MED/ VOL 160, JUNE 26, 2000 2000 American Medical Association. All rights reserved.
either omeprazole or ranitidine, significantly more 12. Sontag SJ, Kugut DG, Fleischmann R, et al. Lansoprazole heals erosive reflux patients treated with omeprazole were heartburn-free at esophagitis resistant to histamine H2-receptor antagonist therapy. Am J Gas-troenterol. 1997;92:429-437.
4, 8, 12, and 16 weeks compared with those treated 13. Sontag SJ, Kogut DG, Fleischmann R, Campbell DR, Richter J, Haber M, for the with ranitidine.31 The overall cost of care during these Lansoprazole Maintenance Study Group. Lansoprazole prevents recurrence of 16 weeks was only $23 higher for those treated with erosive reflux esophagitis previously resistant to H2-RA therapy. Am J Gastro- omeprazole compared with those treated with raniti- dine, primarily as a result of a reduced number of 14. Robinson M, Campbell DR, Sontag S, Sabesin SM. Treatment of erosive reflux esophagitis resistant to H2-receptor antagonist therapy: lansoprazole, a new pro- ton pump inhibitor. Dig Dis Sci. 1995;40:590-597.
In summary, lansoprazole therapy at a dosage of ei- 15. Nwokolo CU, Smith JT, Gavey C, et al. Tolerance during 29 days of conventional ther 15 or 30 mg once daily was significantly more ef- dosing with cimetidine, nizatidine, famotidine, or ranitidine. Aliment Pharmacol fective than ranitidine therapy and placebo in reducing the percentage of days and nights with heartburn, the se- 16. Merki HS, Wilder-Smith C, Walt R, Halter F. The cephalic and gastric phases of gastric acid secretion during H2 antagonist treatment. Gastroenterology. 1991; verity of heartburn, as well as the use of and need for ant- acid therapy among patients with nonerosive esophagi- 17. JM Van Elteren. On the combination of independent two sample tests of Wil- tis. These data suggest that lansoprazole and other proton coxon. Bull Inst Intern Stat. 1960;37:351-361.
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