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, MSBackground: 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;160:1803-1809GASTROESOPHAGEALre- 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. STUDY DESIGN, PATIENTS,
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 (%) Rantidine, Lansoprazole, Lansoprazole, 150 mg Twice Daily 15 mg Once Daily 30 mg Once Daily Characteristic
*From F test. †From 2 test. ‡Includes ex-tobacco users. §Includes ex-alcohol drinkers. Table 2. Summary of Median Diary Data at Baseline Ranitidine, Lansoprazole, Lansoprazole, 150 mg Twice Daily 15 mg Once Daily 30 mg Once Daily Variable
*Statistically significant ( PՅ.05) vs placebo. Pain severity (range, 0-3) was scored as 0 = none, 1 = mild, 2 = moderate, and 3 = severe. SYMPTOM RELIEF
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) Variable 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.
pump inhibitors may be the preferred treatment for any
18. Dorsch E, Jones J, Rose P, Jennings D. Lansoprazole provides superior symp-
patients with reflux disease for whom treatment with life-
tom relief for patients with non-erosive reflux esophagitis [abstract]. Gastroen-terology. 1996;110:A987.
style modifications and over-the-counter H2RAs fails.
19. Richter JE, Kovacs TOG, Greski-Rose PA, Huang B, Fisher R. Lansoprazole in
the treatment of heartburn in patients without erosive esophagitis. Aliment Phar-
Accepted for publication December 8, 1999.This study was supported by a grant from TAP Phar-
20. Shaw MJ, Kane RL, Fendrick AM, Adlis SA, Talley NJ. The impact of over-the-
counter histamine 2-antagonists: great expectations unfulfilled [abstract]. Gas-troenterology. 1998;114:A41. Corresponding author: Joel E. Richter, MD, Depart-
21. Shaw MJ, Beebe TJ, Adlis SA. Health care seeking for dyspepsia in a community
ment of Gastroenterology, The Cleveland Clinic, 95 Euclid
sample: role of the pain experience, comorbid illness and health-related quality
of life [abstract]. Gastroenterology. 1998;114:A40.
22. Bell NJV, Burget D, Howden CW, Wilkinson J, Hunt RH. Appropriate acid sup-
pression for management of gastro-oesophageal reflux disease. Digestion. 1992;
23. Meyer M, Meier J, Drewe J. Effect of lansoprazole and ranitidine on gastric acid-
1. Shaw MJ, Adlis SA, Beebe TJ. When does simple heartburn become a disease
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(REPRINTED) ARCH INTERN MED/ VOL 160, JUNE 26, 2000
2000 American Medical Association. All rights reserved.
ANAT 2160/BIOL 3430 Nervous tissue and cartilage laboratory module 1) Nervous tissue Objectives: 1) understand the structure of neuronal somata (cell bodies) and cytoplasmic processes 2) identify somata and processes of neurons in other tissues in the body 3) identify cell types that support neurons in the central and peripheral nervous systems 4) understand the relationship between pe
Statement given April 10, 2008 Faculty Meeting Marty Wyngaarden Krauss, Provost I want to speak to you about a variety of issues, including some of the issues raised in the March 13 meeting of the Senate, as noted in their minutes. I will defer commentary on the specific issues raised in the preceding reports in order to consider them carefully. I have been a member of this faculty since 1982