Evidence Table 1

Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor

Author
Year
Population, SettingEsophagitis Grade (Grading Criteria), Other CharacteristicsNumber Screened, Eligible, Enrolled, Withdrawn, Lost to FollowupHealing Rate at 4 WeeksHealing Rate at 8 WeeksSymptoms at 4 WeeksSymptoms at 8 WeeksResults by Baseline SeverityWithdrawals Due to Adverse EventsQuality ratingFunding source
Adachi et al, 200385 patients at 6 medical institutions in Japan. Mean age 66 (SD 13); 51% male; 100% AsianGrade A: 24%
Grade B: 53%
Grade C: 21%
Grade D: 2%
(Los Angeles classification)
42% h. Pylori positive
Screened NR/eligible
NR/85 enrolled
20% of lansoprazole group lost to f/u for endoscopy vs 7% in other groups; but no loss to f/u for reporting of symptoms 85 analyzed for symptoms, 76 for endoscopy
Not reported(Per protocol analysis on 76 patients):
omeprazole 20 mg: 85.7%
lansoprazole 30 mg: 85%
rabeprazole 20 mg: 92.9%
(NS)
(Results reported graphically only)
Heartburn score significantly lower in rabeprazole group after 2 days than lansoprazole or omeprazole (p=0.045).
Differences disappeared by day 5.
No significant differences in acid reflux scores.
Not reportedNot reportedNot reportedFair:
open-label, loss to f/u higher in lansoprazole group for healing (20% vs 7%), but okay for symptoms; randomization method not reported
Ministry of Education, Science, and Culture of Japan
Bardhan et al, 2001328 patients at 23 centers in Great Britain, the Republic of Ireland, and South Africa.
Mean age 44.6 (SD 13.3) in pantoprazole group, 45.2 (SD14.4) in omeprazole group.
52.4% of pantoprazole, 64% of omeprazole group males.
Race/ethnicity not reported.
100% Grade I
(Savary-Miller classification)
Screened NR/eligible
NR/328 enrolled/327 analyzed
Intention-to-treat (N=327):
pantoprazole 20 mg: 77%
omeprazole 20 mg: 81%

Per-protocol (N=264):
pantoprazole 20 mg: 84%
omeprazole 20 mg: 89%
Intention-to-treat (N=327):
pantoprazole 20 mg: 81%
omeprazole 20 mg: 88%
(NS)

Per-protocol (N=264):
pantoprazole 20 mg: 90%
omeprazole 20 mg: 95%
(NS)
pantoprazole 20 mg vs omeprazole 20 mg
Symptom relief (all main symptoms)
2 weeks: 70% vs 79%
4 weeks: 77% vs 84%
Acid eructation
2 weeks: 79% vs 88%
4 weeks: 84% vs 87%
Heartburn
2 weeks: 79% vs 86%
4 weeks: 83% vs 87%
Pain on swallowing
2 weeks: 83% vs 87%
4 weeks: 87% vs 97%
(All NS)
Not reportedRelief of acid eructation, heartburn and pain on swallowing was similar in the two treatment groups at 2 and 4 weeks, irrespective of severity at baseline.
A higher proportion with mild symptoms at entry had relief compared with patients with severe symptoms, and this was similar for both treatments.
Not reportedFair-Poor:
open-label, randomization, allocation concealment method not reported, more smokers in pantoprazole group (31% vs 22%), more males in omeprazole group (64% vs 52%)
Byk Gulden (Germany)
pharmaceutical
Chen et al, 200548 patients at a single center in Taiwan.
Mean age 53.9
79.2% male
Race NR
Grade A: 54.2%
Grade B: 29.2%
Grade C: 8.3%
Grade D: 8.3%
(Los Angeles classification)
Screened, eligible
NR/48 enrolled
2 withdrawn/2 lost to followup/42 analyzed per protocol, 47 analyzed ITT
esomeprazole 40 mg: NR
omeprazole 20 mg: NR
PP patients (n=42)
esomeprazole 40 mg: 72.7%
omeprazole 20 mg: 50%

ITT patients (n=47)
esomeprazole 40 mg: 64%
omeprazole: 20 mg: 45.5%

OR 2.667 (PP: 95% CI 0.739–9.63, P=0.2040)
NRHeartburn:
esomeprazole 40 mg: 50% improved, 50% no change
omeprazole 20 mg: 65% improved, 25% no change, 10% worse
(p=0.0993)
Regurgitation:
esomeprazole 40 mg: 77.3% improved, 18.2% no change, 4.5% worse
omeprazole 20 mg: 85.0% improved, 15.0% no change
(p=1.0000)
Dysphagia:
esomeprazole 40 mg: 36.4% improved, 63.6% no change
omeprazole 20 mg: 35.0% improved, 60.0% no change, 5.0% worse
(p=0.8697)
Epigastric pain:
esomeprazole 40 mg: 27.3% improved, 63.6% no change, 9.1% worse
omeprazole 20 mg: 50.0% improved, 50.0% no change
(p=0.1895)
Nausea:
esomeprazole 40 mg: 22.7% improved, 68.2% no change, 9.1% worse
omeprazole 20 mg: 35.0% improved, 65.0% no change
(p=0.5036)
Vomiting:
esomeprazole 40 mg: 22.7% improved, 77.3% no change
omeprazole 20 mg: 40.0% improved, 60.0% no change
(p=0.3200)
Belching:
esomeprazole 40 mg: 54.5%, 36.4% no change, 9.1% worse
omeprazole 20 mg: 45.0% improved, 45.0% no change, 10.0% worse
(p=0.8999)
Not quantitatively expressed, see Figure 1.
Difference stated as not SS different.
NRFairNR (AstraZeneca provided randomization schedule)
Fennerty, 2005999 patients at multiple centers in the US, with moderate to severe esophagitis.
Mean age 47
66% male
82% white, 5% black, <1% Asian, 13% other
Grade C: 79%
Grade D: 21%
(Los Angeles classification)
4015 screened/
1381 eligible/
1001 enrolled/
11 withdrew/
18 lost to followup/
999 analyzed
esomeprazole 40 mg: 55.8%
lansoprazole 30 mg: 47.5%
(p<0.005)
esomeprazole 40 mg: 77.5%
lansoprazole 30 mg: 73.3%
(p=0.099)
Resolution of heartburn:
esomeprazole 40 mg: 72%
lansoprazole 30 mg: 63.6%
(p=0.005)
Resolution of acid regurgitation:
esomeprazole 40 mg: 79.5%
lansoprazole 30 mg: 76.2%
(p=0.203)
Dysphagia:
esomeprazole 40 mg: 93.1%
lansoprazole 30 mg: 93.8%
(p=0.614)
Epigastric pain:
esomeprazole 40 mg: 83.1%
lansoprazole 30 mg: 82.6%
(p=0.831)
Not reportedGrade C
Healing at 4 weeks
esomeprazole 40 mg: 60.3%
lansoprazole 30 mg: 50.6%
(p-value not reported)
Healing at 8 weeks
esomeprazole 40 mg: 80.3%
lansoprazole 30 mg: 74.9%
(p-value not reported)
Grade D
Healing at 4 weeks
esomeprazole 40 mg: 39.8%
lansoprazole 30 mg: 34.7%
(p-value not reported)
Healing at 8 weeks
esomeprazole 40 mg: 67.6%
lansoprazole 30 mg: 66.3%
(p-value not reported)
5/499 (1%)
esomeprazole vs 9/502 (2%) lansoprazole.
Most common adverse event leading to study withdrawal was abdominal pain (two in each group)
GoodAstraZeneca
Gillessen, 2004227 patients at 27 centers in Germany.
Mean age 53 (SD 15) in pantoprazole group, 54 (SD 14) in esomeprazole group.
57% of pantoprazole, 50% of esomeprazole group male.
97% of pantoprazole, 98% of esomeprazole group Caucasian (others Asian)
Grade B: 84% pantoprazole, 83%
esomeprazole
Grade C: 16% pantoprazole, 17%
esomeprazole
(Los Angeles classification)
Screened NR/eligible
NR/227 enrolled/227
analyzed ITT/197
analyzed per protocol
“Early time points” (4 and 6 weeks)
Intention-to-treat (N=227):
pantoprazole 40 mg: 74%
esomeprazole 40 mg: 72%
(NS)
Per-protocol (N=197):
pantoprazole 40 mg: 78%
esomeprazole 40 mg: 74%
(NS)
“Late time points” (8 and 10 weeks)
Intention-to-treat (N=227):
pantoprazole 40 mg: 90%
esomeprazole 40 mg: 92%
(NS)
Per-protocol (N=197):
pantoprazole 40 mg: 96%
esomeprazole 40 mg: 93%
(NS)
Overall relief of symptoms
Per-protocol (N=197):
pantoprazole 40 mg: 37%
esomeprazole 40 mg: 35%
(NS for PP or ITT)
Overall relief of symptoms
Per-protocol (N=197):
pantoprazole 40 mg: 47%
esomeprazole 40 mg: 32%
(NS for PP or ITT)

After 10 weeks:
pantoprazole 40 mg: 65%
esomeprazole 40 mg: 63%
(NS for PP or ITT)
Per-protocol, overall healing by baseline grade
Grade B:
pantoprazole 40 mg: 92%
esomeprazole 40 mg: 95%
Grade C:
pantoprazole 40 mg: 67%
esomeprazole 40 mg: 45%

Among patients diagnosed with grade C at baseline, 100% of pantoprazole and 91% of esomeprazole improved to Grade A or B at final visit.
6 patients overall, not reported by group.Fair:
Randomization, allocation concealment method not reported.
Altana Pharma, Germany
Kao et al, 2003100 patients at one center in Taiwan
mean age 49
69% male
100% Asian
Grade A: 51%
Grade B: 49%
(Los Angeles Classification)
Screened NR/eligible
NR/100 enrolled
Not reportedNot reportedEsomeprazole 40 mg vs omeprazole 20 mg
Per-protocol (N=91)
Symptom-free on day 1: 28.2% vs 26.2% (NS)
Symptom-free before week 1: 56.4% vs 55.6% (NS)
Median days to symptom resolution: 4 vs 4 (NS)
Achievement of sustained symptom response
Week 1: 15.2% vs 15.6% (NS)
Week 2: 50% vs 20% (p<0.05)
Week 3: 71.7% vs 40% (p<0.01)
Week 4: 73.9% vs 51.1% (p<0.05)
Week 4 (intention-to-treat): 68% vs 46% (p<0.05)
Efficacy of on-demand therapy (n=34 esomeprazole 40 mg, n=23 omeprazole 20 mg, initiated week 5)Not reportedNot reportedFair:
not clear if patients masked, randomization, allocation concealment methods not reported.
Supported by a grant from the National Cheng Kung University
Castell
1996
1070 US patients at multiple centers (number excludes placebo), mean age 47, (range 18–84); 60–68.4% male; 85% white, 9% black, 5% Hispanic.Grade 2: 61%–71%
Grade 3: 24%–30%
Grade 4: 6%–9%
(See Appendix F for scale)
6.5%–8.7% Barrett’s esophagus
1284 enrolled, 1226 analyzed (total with placebo)lansoprazole 15 mg: 72.0%
lansoprazole 30 mg: 79.6%
omeprazole 20 mg: 87.0%
lansoprazole 30 mg vs lansoprazole 15 mg
p<.05
omeprazole 20 mg vs lansoprazole 15 mg
p<.05
Other comparisons NS
lansoprazole 15 mg: 75.2%
lansoprazole 30 mg: 87.1%
omeprazole 20 mg: 87.0%
lansoprazole 30 mg vs lansoprazole 15 mg
p<.05
Omeprazole 20 mg vs lansoprazole 15 mg
p<.05
Other comparisons NS
Not givenMedian percentage of days with heartburn:
lansoprazole 15 mg: 12.3%
lansoprazole 30 mg: 8.6%
omeprazole 20 mg: 11.8%
Median percentage with heartburn:
lansoprazole 15 mg: 9.3
lansoprazole 30 mg: 6.5
(not ITT)
lansoprazole15 mg vs omeprazole 20 mg p<0.05 nights
lansoprazole15 mg vs lansoprazole 30 mg p< days and nights
All other comparisons NS
When healing rates were adjusted for baseline esophagitis grade, treatment comparison results were similar to those of the overall analyses.
Patients with less severe esophagitis (grade 2) at baseline had higher rates with all the active treatments than those with more severe disease (grades 3 and 4).
Healing rate at 4 weeks, lansoprazole 15 mg vs lansoprazole 30 mg vs omeprazole 20 mg, by baseline esophagitis grade:
grade 2: 83.2% vs 89.4% vs 88.2%
grades 3 and 4: 59.5% vs 73.5% vs 69.8%
at 8 weeks, lansoprazole 15 mg vs lansoprazole 30 mg vs omeprazole 20 mg, by baseline esophagitis grade::
grade 2: 87.8% vs 94.3% vs 91.6%
grades 3 and 4: 62.5% vs 85.3% vs 88.7%
omeprazole 20 mg: 2%
lansoprazole 30 mg: 1.7%
lansoprazole 15 mg: 0.9%
Fair: randomization and allocation method not reported, attrition not reportedSupported by TAP Pharmaceuticals, Inc.
Castell et al, 20025241 patients, multiple centers, mean age 47 (range 18–75), 57% male, 91% white, 6% black, 3% other.Grade A: 36%
Grade B: 40%
Grade C: 18%
Grade D: 6%
(LA Grade)

Heartburn Severity
None: 1%
Mild: 10%
Moderate: 47%
Severe: 42%
5241 enrolled, ITT

Number screened NR

lansoprazole 30 mg (n=2617)
esomeprazole 40 mg (n=2624)
esomeprazole 79.4%
lansoprazole 75.1%
(p<.001)
(life-table analysis)
EE
esomeprazole 92.6%
lansoprazole 88.8%
(p=.0001)
(life-table analysis)
Complete resolution of heartburn:
lansoprazole 60.2%
esomeprazole 62.9% (p<.05)

Heartburn-free nights:
lansoprazole 85.8%
esomeprazole 87.1% (p<.05)

Heartburn-free days: NS
Not reportedesomeprazole 75.7%
lansoprazole 71.7%
(p<0.01, stratified by baseline severity)

esomeprazole 87.6%
lansoprazole 84.2%
(p<0.01, stratified by baseline severity)
No difference in treatment-related adverse effects.

Withdrawal due to adverse event 1.8% vs. 1.9%.
GoodSupported by AstraZeneca, also listed in author credits
Corinaldesi
1995
241 patients at 30 centers, Belgium, France, Italy, the Netherlands, median age 50–52, (range 18–88); 63% male; ethnicity not given.Grade 2: 82%
Grade 3: 18%
(Savary-Miller)
Number screened not given, 241 randomized, 208 evaluable; 3 withdrew, 23 did not attend f/u.pantoprazole 40 mg: 67.5%
omeprazole 20 mg: 68.6%
p=NS
pantoprazole 40 mg: 80.8%
omeprazole 20 mg: 79.3%
p=NS
Heartburn free:
omeprazole 20 mg: 82.2%
pantoprazole 40 mg: 87.9%
p=NS
Not reportedNot reportedpantoprazole 40 mg: 0.8%
omeprazole 20 mg: 1.7%
Poor: randomization and allocation method not reported, no intention-to-treat analysis, baseline characteristics not analyzed.Last author from Byk Gulden Pharma ceuticals, study supported by same.
Dekkers
1999
202 patients of 27 investigators in 10 European countries, mean age 53 + 15.63, (range 20–86); 62% male; ethnicity not given.Grade 2: 43%
Grade 3: 52%
Grade 4: 4%
(modified Hetzel-Dent)
Number screened not given, 202 enrolled, 192 completed.rabeprazole 20 mg: 81%
omeprazole 20 mg: 81%
(Not ITT)
p=NS
rabeprazole 20 mg: 92%
omeprazole 20 mg: 94%
(Not ITT)
p=NS
Heartburn frequency (resolution):
rabeprazole 20 mg: 29.6%
omeprazole 20 mg: 26.5%
Daytime severity (resolution):
rabeprazole 20 mg: 61.9%
omeprazole 20 mg: 60.8%
Nighttime severity resolution:
rabeprazole 20 mg: 61.6%
omeprazole 20 mg: 57.3%
p=NS for all
Heartburn frequency resolution:
rabeprazole 20 mg: 37.8%
omeprazole 20 mg: 31.4%
Daytime severity resolution:
rabeprazole 20 mg:68.0%
omeprazole 20 mg: 66.0%
Nighttime severity resolution:
rabeprazole 20 mg: 64.4%
omeprazole 20 mg: 66.7%
p= NS for all
Not reportedrabeprazole 20 mg: 1%
omeprazole 20 mg: 0
Fair: randomization and allocation method not reported intention-to-treat for symptoms only, not for healing.Last author (corresponding author) and 5th authors with Eisai Ltd, funding info not given.
Delchier
2000
300 patients of 61 investigators at 50 European centers, mean age 53 (+15), (range 18–80); 62% male; ethnicity not given.Mean grade 2.6–2.7, median 3.9, (modified Hetzel-Dent)
7% had Barrett’s esophagus, 41% positive for H. pylori
358 screened, 310 randomized, 298 completed.rabeprazole 20 mg: 88.5%
rabeprazole 10 mg: 85.4%
omeprazole 20 mg: 91.2%
p=NS
rabeprazole 20 mg: 91.3%
rabeprazole 10 mg: 91.3%
omeprazole 20 mg: 94.2%
p=NS
Severity of daytime and nighttime
heartburn: p=NS (numbers not given)
Severity of daytime and nighttime heartburn: p=NS (numbers not given)No statistically significant differences between treatment groups after controlling for baseline factors including Hetzel-Dent grade (other factors sex, age, smoking and H. pylori status); data not reported.rabeprazole 10 mg: 5%
rabeprazole 20 mg: 5%
omeprazole 20 mg: 2%
Fair: randomization and allocation method not reported, followup somewhat high (76%–83%).Funded by Eisai Ltd, London, last author (corresponding author) from Eisai
Dupas
2001
461 patients at 29 hospital centers and 45 private practices in France; mean age 54 (+14.6); 74% male; ethnicity not given83% Grade 2
17% Grade 3 (Savary-Miller)
Number screened not given; 461 randomized, 385 completedpantoprazole 40 mg
ITT: 80.90%
lansoprazole 30 mg
ITT: 80%
p=NS
pantoprazole 40 mg
ITT: 89.80%
lansoprazole 30 mg
ITT: 90%
p=NS
Symptom free (all symptoms - heartburn, acid regurgitation, pain or swallowing):
ITT:
pantoprazole 40 mg: 83%
lansoprazole 30 mg: 92%
p=NS
Not reportedFor both treatments, healing rates after 4 weeks were lower in grade III than in grade II esophagitis (69% vs 89%, per-protocol analysis, p=0.0001), with no grade-dependent significant differences between groups.pantoprazole 40 mg:
13%
lansoprazole 30 mg:
2.5%
Fair: randomized method not clear, allocation method not reportedFunded by BYK
France, last author from BYK
Hatlebakk
1993
229 patients at 9 hospitals in Norway and Sweden; mean age 55; 66% male; ethnicity not givenlansoprazole 30 mg group:
Grade 0: 2.6%
Grade 1: 34.5%
Grade 2: 50.9%
Grade 3: 12.1%
omeprazole 20 mg group:
Grade 0: 2.7%
Grade 1: 38.9%
Grade 2: 55.8%
Grade 3: 2.7%
(See Appendix E for scale)
Number screened not given, 229 enrolled.lansoprazole 30 mg: 61.2%
omeprazole 20 mg: 64.6%
p=NS
lansoprazole 30 mg: 81.9%
omeprazole 20 mg: 85.0%
p=NS
Data not given:
states lansoprazole 30 mg had greater improvement in heartburn (p=0.03)
Data not given, but states no significant differences in any symptoms.At both 4 and 8 weeks, and irrespective of treatment, healing rates were higher for patients with grade 1 esophagitis than grade 2 (p<0.01, two-stage logistic regression analysis). Results by treatment group not reported.omeprazole 20 mg: 0.9%
lansoprazole 30 mg: 0
Poor: randomization and allocation method not reported, no intention-to-treat analysis, eligibility criteria not specified, some differences at baseline.Not reported
Holtmann,
2002
251 patients at multiple centers in Germany, Denmark, and Switzerland; mean age 52; 66% male, 99% Caucasian.rabeprazole: 78% grade II, 22%
grade III; omeprazole: 84% grade II, 16% grade III
274 screened/254 eligible, 251 enrolled/13 withdrawn or no valid data/4 lost to followup/251 analyzedNo difference between groups (data not reported)per protocol (N=200)
rabeprazole 20 mg: 92.7%
omeprazole 40 mg: 89.2%
(NS)
Not reported for this time point;
difference in relief from heartburn on day 4 not significant between groups.
Not reported for this time point.Healing rate in patients with GERD grade III (N=45)
4 weeks: 84% rabeprazole vs 72.2% omeprazole
(NS)
8 weeks: 88% rabeprazole vs 77.8% omeprazole
(NS)
4/125 (3%) rabeprazole vs 2/126 (2%)
omeprazole
Fair: Not clear if randomization method adequate, allocation concealment method not reported, more rabeprazole patients grade III esophagitis at baseline (22% vs 16%).Funded by Eisai and Janssen-Cilag
Howden et al,
2002
284 patients at multiple centers, mean age 46.5 (range 19–78), 56% male, 80% white, 5% black, 15% other.Grade 2: 61%
Grade 3:30%
Grade 4: 8% (see Appendix F for scale)
284 enrolled; # screened, eligible not reported, 277 evaluated

lansoprazole 30 mg
(n=139)
esomeprazole 40 mg
(n=138)
lansoprazole 30 mg vs esomeprazole 40 mg
77.0% vs 78.3% (p=NS)
lansoprazole 30 mg vs esomeprazole 40 mg 91.4% vs 89.1% (95% CI of difference −4.7, 9.2)Not reportedNot reportedHealing rate or improvement of 2 grades at 8 weeks by baseline grade, lansoprazole 30 mg vs esomeprazole 40 mg:
Grade 2: 94.3% (82/87) vs 95.1% (77/81)
Grade 3: 92.7% (38/41) vs 81.8% (36/44)
Grade 4: 90.9% (10/11) vs 84.6% (11/13)

Week 4 healing: healing or improvement of 2 grades of erosive esophagitis from baseline were comparable between treatment groups, regardless of baseline grade of esophagitis (data not reported).
2/143 (1.4%) lansoprazole vs 5/141 (3.5%) esomeprazoleFair: randomization and allocation concealment methods not reported.Supported by TAP Pharmaceuticals.
Kahrilas
2000
1960 US patients at 140 centers; mean age 46; 60% male; ethnicity not given.Grade A: 33%
Grade B: 40%
Grade C: 19%
Grade D: 7%
(Los Angeles classification)
9.6% H. pylori
3354 screened, 1960 randomized. 44 did not complete study due to an adverse event and 115 for other reasons including loss to f/u and withdrawal of consent.esomeprazole 40 mg: 75.9%
esomeprazole 20 mg: 70.5%
omeprazole20: 64.7%
(cumulative life table rate)
esomeprazole 20 mg vs omeprazole 20 mg p=0.09
esomeprazole 40 mg vs omeprazole 20 mg (p <0.05)
esomeprazole 40 mg: 94.1%
esomeprazole 20 mg: 89.9%
omeprazole 20 mg: 86.9%
(cumulative life table rate)
esomeprazole 40 mg vs omeprazole 20 mg p<0.001
esomeprazole 20 mg vs omeprazole 20 mg p<0.05
Resolution of heartburn
esomeprazole 40 mg: 64.7%
esomeprazole 20 mg: 61.0%
omeprazole 20 mg: 57.2%
esomeprazole 40 mg vs omeprazole
20 mg p=0.005
other comparisons NS
"Cumulative analysis at week 8 not done because pts could complete the study at week 4 with healed reflux esophagitis, even if symptoms were present"Greater efficacy of esomeprazole 40 mg vs omeprazole 20 mg at 4 weeks was consistent when adjusting for baseline esophagitis grade (data not reported).esomeprazole 40 mg: 2%
esomeprazole 20 mg: 2.6%
omeprazole 20 mg: 2%
Fair: Randomization methods not reported, baseline characteristics not analyzed, more grade
A patients (mild) in esomeprazole 40 mg group than omeprazole 20 mg group at baseline (35.9% esomeprazole vs 31.2% omeprazole 20 mg; calculated p = 0.07).
4 of 9 authors from Astra Zeneca, study supported by grant from Astra Zeneca.
Korner et al,
2003
669 patients at multiple centers, mean age 53.8 (sd 14), 60% male, ethnicity not reported.84% Grade II
16% Grade III
(Savary-Miller)
669 included; number screened, eligible not reported.
Pantoprazole 40 mg (n=337)
omeprazole MUPS 40 mg (n=332)
ITT results reported as odds ratios only.
PP results, pantoprazole 40 mg (n=282) vs omeprazole MUPS 40 mg (n=270) 70.9% vs 72.6%
ITT results reported as odds ratios only.
"Healing rates after 8 weeks of treatment were also similar in both Heartburn relief: groups."
ITT results not reported PP,
pantoprazole 40 mg vs omeprazole MUPS 40 mg:
83.7% vs 88.1%
Relief of pain on swallowing:
83.1% vs 91.9%
(p-values not reported)
ITT results not reported
PP, pantoprazole 40 mg vs omeprazole MUPS 40 mg:
Heartburn relief:
91.1% vs 92.6%
Relief of pain on swallowing:
94.1% vs 96.3%
(p-values not reported)
Not reported (all patients were Grade II or III)4/337 (1%) pantoprazole, 7/332 (2%) omeprazole MUPSFair: ITT results not reported, randomization and allocation concealment methods not reported.Supported by a grant from ALTANA Pharma AG, Germany.
Labenz et al,
2005
3151 patients, multinational, mean age 50.6 (sd 14), 63% male, 97% Caucasian.Grade A: 32%
Grade B: 44%
Grade C: 19%
Grade D: 5%
(LA Classification)
3170 randomized, 3151 analyzed. 9 excluded from analysis because of intake of an unknown study drug, and 10 because of study protocol violations.esomeprazole 40 mg vs pantoprazole 40 mg
Observed (per protocol):
78.8% vs 72.8%
risk difference 6% (95% CI 3%, 9%)

Life table analysis, per protocol:
81.0% vs 74.5% (p<0.001)
esomeprazole 40 mg vs pantoprazole 40 mg
Observed (per protocol):
91.6% vs 88.9%
risk difference 3% (95% CI 1%, 5%)

Life table analysis, per protocol:
95.5% vs 92.0% (p<0.001)
esomeprazole 40 mg vs pantoprazole 40 mg Time to achieve sustained heartburn resolution (defined as the first of 7 consecutive days with no heartburn):
6 days vs 8 days (p<0.001)
esomeprazole 40 mg vs pantoprazole 40 mg
Proportion of heartburn-free days:
70.7% vs 67.3% (p<0.01)
Healing of esophagitis by baseline grade, esomeprazole 40 mg vs pantoprazole 40 mg
Week 4, (Observed, per protocol):
Grade A: 83.9% vs 83.1% (NS)
Grade B: 80.2% vs 75.4% (p<0.05)
Grade C: 71.1% vs 60.1% (p<0.01)
Grade D: 61.4% vs 40.2% (p<0.01)

Week 8 (Life table analysis, per protocol):
Grade A: 97.3% vs 97.1% (NS)
Grade B: 96.9% vs 93.1% (p<0.05)
Grade C: 91.3% vs 87.6% (p<0.01)
Grade D: 88.1% vs 73.6% (p<0.05)
2.1% esomeprazole,
1.8% pantoprazole
Fair/Poor:
Randomization and allocation concealment methods not reported. Post-randomization exclusions (19 patients) and no data on excluded patients. Baseline data excludes 19 patients randomized but excluded due to intake of an unknown study drug or protocol violations. No data on excluded patients. Some differences in baseline esophagitis grade at baseline (grade B: 42.6% esomeprazole vs 45.1% pantoprazole; grade D: 4.5% esomeprazole, 5.8% pantoprazole).
AstraZeneca
Lightdale, 20061176 patients, multicenter, 63.6% male, 91.8%
Caucasian, mean age 45 yrs
Grade A: 37%
Grade B: 36.4%
Grade C: 19%
Grade D: 7.5%
(LA clasification)
1876/NR/1106/47/23Life table analysis: esomeprazole
20 mg vs. pantoprazole 20 mg
68.7% vs 69.5%
Life table analysis
90.6% vs. 88.3%, p=0.621 (log rank test)
esomeprazole vs omeprazole
resolution of heartburn: 60.6 vs 60.5% ; p=0.995
Proprotion of heart burn free days:
72.6% vs. 70.9%p=0.354
Proportion of hear burn free nights:
85.7% vs. 83.2%, p=0.354
NR healing rate acroos baseline grade at week 8
20 mg esomeprazole vs 20 mg omeprazole
Grade A: 94.6% vs. 87.7%
Grade B: 85.0% vs 84.7%
Grade C: 78.5% vs. 72.8%
Grade D: 73.0% vs. 68.6%
All: 86.5% vs 82.3% (p=0.052)
esomeprazole=1.5%
omeprazole=1.7%
GoodAZ
Pace et al, 2005549 patients, multi center Italy, mean age 47.4 (sd 14), male 68.1%Grade 0: 1%
Grade 1: 69%
Grade 2: 24%
Grade 3: 5.5%
Grade 4: 0%
(Savary-Miller)
Screened NR, Eligible NR, Enrolled 560, Withdrawn 47, lost to f/u 9rabeprazole 20 mg: PP 91.0%, omeprazole 20 mg: PP 89.9%, equivalence bet. the two drugs is statistically significant (p<0.001)rabeprazole 20 mg: PP 97.9%, omeprazole 20 mg: PP 97.5%, equivalence bet. the two drugs is statistically significant (p<0.0001)ITT population, mean time to the first day w/satisfactory heartburn relief, rabeprazole (n=271) 2.8+−0.2 days, omeprazole (n=271) 4.7+−0.5 days (p=0.0045), mean time to complete heartburn relief, rabeprazole 7.2 days, omeprazole 8.4 days (p=NS).
Patients w/complete heartburn relief (day and nighttime) in each day of first week of treatment (ITT patients) Rabeprazole n=245 32.2%, Omeprazole n=243 18.9%
NRHealing rates of oesophagitis grade at endpoint (4 or 8 weeks), rabeprazole vs omeprazole: grade I: 99.4 vs. 98.8%, grade II: 95.1 vs. 96.4%, grade III: 91.7 vs. 86.7% (PP patients)No significant difference bet. Treatment groups in single adverse event occurring, with exception of headache (Omeprazole 4.8% and Rabeprazole 1.4%)Fair. Lack of ITT analysis, exclusion of people (2%) at baseline.Janssen-Cilag, Italy
Mee
1996
604 patients at multiple centers, UK and Ireland, mean age 53; 67% male; ethnicity not given.Grade 1: 39%
Grade 2: 44%
Grade 3: 15%
Grade 4: 2%
(Savary-Miller)
604 enrolled, 565 eligible, 537 evaluablelansoprazole 30 mg: 62%
omeprazole 20 mg: 56.6%
p=NS
lansoprazole 30 mg: 75.3%
omeprazole 20 mg: 71.1%
p=NS
Not givenImprovement in daytime epigastric pain
lansoprazole 30 mg: 85.9%
omeprazole 20 mg: 72.5%
Improvement in nighttime epigastric pain
lansoprazole 30 mg: 85.9%
omeprazole 20 mg: 67.3%
p=NS
(includes only pts who attended 8-week visit who reported baseline pain)
Healing of esophagitis by baseline grade, lansoprazole vs omeprazole:
Week 4:
Grade I: 79% vs 68%
Grade II: 72% vs 62%
Grade III: 45% vs 57%
Grade IV: 43% vs 60%
Week 8 (cumulative):
Grade I: 92% vs 87%
Grade II: 88% vs 81%
Grade III: 73% vs 72%
Grade IV: 50% vs 50%

Esophagitis grade and treatment were included in a logistic regression model. Odds ratio of healing on lansoprazole compared with omeprazole was 1.46 (95% CI 0.87, 2.45)
Not reportedGood/Fair: Allocation concealment method not given.1 of 2 authors from Lederle Laboratories, funding info not given.
Mulder
1996
211 patients at multiple centers in The Netherlands; mean age 55; 70% male; ethnicity not given.Grade 1: 0.47% (1 patient)
Grade 2: 68%
Grade 3: 24%
Grade 4A: 8%
(Savary-Miller)
Number screened not given, 211 enrolled, 3 lost to followup, 3 withdrew for lack of efficacy, 1 withdrawn for receiving double dose.lansoprazole 30 mg
ITT
85.50%
PP
86.20%
omeprazole 40 mg
ITT
79%
PP
79.6%
p=NS
lansoprazole 30 mg
ITT:
93.40%
PP
95.70%
omeprazole 40 mg
ITT:
90.50%
PP
93.4%
p=NS
lansoprazole 30 mg
No symptoms:
ITT:
73.60%
omeprazole 40 mg
No symptoms:
ITT
71.40%
“Because of the low number of patients not healed at 4 weeks, analysis of symptoms was not performed at 8 weeks.”Healing of esophagitis by baseline grade, lansoprazole vs omeprazole:
Week 4:
Grade II: 90.8% vs 88.1%
Grade III/IV: 81.5% vs 70.6%
overall:
Grade II: 97.4% vs 98.5%
Grade III/IV: 92.6% vs 85.3%
(All NS)
NoneFair: randomization and allocation concealment not reported,Supported by Hoechst Marion Roussel BV and Janssen-Cilag BV, Netherlands
Mulder et al.
2002
461 patients, multiple centers; mean age 51.2 (range 18–80);59% male; ethnicity NRSavary-Miller class:
I: 59%
II: 29%
III: 8%
IVa: 4%

Heartburn Severity
None: 4%
Mild: 22%
Moderate: 45%
Severe: 29%
461 enrolled

Number screened NR

omeprazole MUPS 20 mg (n=151)
lansoprazole 30 mg (n=156)
pantoprazole 40 mg (n=154)
NRNR(omeprazole vs lansoprazole vs pantoprazole)
Heartburn relief: 84% vs. 78% vs. 84%
omeprazole vs lansoprazole 90% CI − 1.44 to 13.24
pantoprazole vs lansoprazole 90% CI − 1.07 to 13.49
Satisfied: 79% vs. 76% vs. 79%.
omeprazole vs lansoprazole 90% CI − 4.04 to 11.68
pantoprazole vs lansoprazole 90% CI − 4.94 to 10.80
pantoprazole vs omeprazole 90% cI − 4.12 to 7.13
(omeprazole vs lansoprazole vs pantoprazole)
Heartburn relief: 87% vs. 81% vs. 89%
pantoprazole vs omeprazole 90% CI −4.55 to 7.64
omeprazole vs lansoprazole 90% CI −0.79 to 12.81
pantoprazole vs lansoprazole 90% CI 0.94 to 14.17
Satisfied: 89% vs. 86% vs. 91%
omeprazole vs lansoprazole 90% CI −2.68 to 9.69
pantoprazole vs lansoprazole 90% CI −0.97 to 10.99
pantoprazole vs omeprazole 90% CI −4.12 to 7.13
Symptom relief at 4 and 8 weeks was similar for each grade of esophagitis.
Maintenance phase (with omeprazole 20 mg or 40 mg only, N=391): symptom relief with omeprazole 20 mg was independent of initial severity of esophagitis; the number of patients in the omeprazole 40 mg maintenance group (N=21) was too small to be divided by initial esophagitis grade.
No difference in AEs between groups. None considered treatment related.

Total withdrawals due to AE: 6/461 (1.3%)

Total AEs: 73/461 (15.8%)
Fair: randomization and allocation methods not reported. More withdrawals in L group.Supported by AstraZeneca
Richter et al, 2001a2425 patients at 163 US centers; mean age 47 (sd 12); 61% male; ethnicity 93.5% Caucasian.Grade A: esomeprazole 40 mg 35%; omeprazole 20 mg 32%
Grade B: esomeprazole 40 mg 39%; omeprazole 20 mg 42%
Grade C: esomeprazole 40 mg 21%; omeprazole 20 mg 20%
Grade D: esomeprazole 40 mg 5%; omeprazole 20 mg 7%
(LA classification)
4798 screened, 2425 randomized; 109 did not complete: 24 for adverse events, 25 investigator-initiated decision, 25 lost to followup, 31 consent withdrawn, 4 lack of therapeutic response.esomeprazole 40 mg vs omeprazole 20 mg
cumulative life table rate:
81.7% vs 68.7% (p<0.001)

Crude rates:
78.6% vs 66.6% (p = 0.001 for CMH test)
risk difference 12% (95% CI 9%, 16%)
esomeprazole 40 mg vs omeprazole 20 mg
cumulative life table rate:
93.7% vs 84.2% (p<0.001)

Crude rates:
89.9% vs 81.0% (p = 0.001 for CMH test)
risk difference 9% (95% CI 6%, 12%)
esomeprazole 40 mg resolution of heartburn:
68.30%
omeprazole 20 mg resolution of heartburn:
58.10%
“Cumulative analysis at week 8 not done because pts could complete the study at week 4 with healed reflux esophagitis, even if symptoms were present”Greater efficacy of esomeprazole 40 mg vs omeprazole 20 mg at 4 weeks was consistent when adjusting for baseline esophagitis grade.

Week 4 healing rates by baseline esophagitis grade (approximate, estimated from figure):
esomxeprazole 40 mg vs omeprazole 20 mg:
Grade A: 88% vs 82%
Grade B: 79% vs 66%
Grade C: 71% vs 53%
Grade D: 55% vs 35%

Week 8 healing rates by baseline esophagitis grade (approximate, estimated from figure):
esomeprazole 40 mg vs omeprazole 20 mg:
Grade A: 93% vs 91%
Grade B: 90% vs 82%
Grade C: 88% vs 70%
Grade D: 80% vs 62%
(p=0.001 for CMH test, esomeprazole vs omeprazole)
1% in each groupGoodSupported by Astra Zeneca, one or more authors from Astra Zeneca.
Richter et al., 2001b3510 patients, multiple centers, mean age 47 (range 18–89); 57% male, 88% white, 5% black, 7% other.Grade 0: <1%
Grade 1: 0%
Grade 2: 68%
Grade 3: 25%
Grade 4: 7%
(See Appendix F for scale)
3410 enrolled; number screened, eligible not reported.Not evaluatedNot evaluatedlansoprazole 30 mg vs omeprazole 20 mg
Sustained resolution of heartburn:
77.2% vs 76.2% (p=NS)
lansoprazole 30 mg vs omeprazole 20 mg
Sustained resolution of heartburn:
84.3% vs 83.0% (p=NS)
More patients talking lansoprazole did not have a single episode of day or night heartburn (between 10% and 15%, p<0.05, data are presented graphically only)
Not reported40/1754 (2%)
lansoprazole 33/1756
(2%)omeprazole.
Fair: ITT results not reported, randomization and allocation concealment methods not reported.Supported by a grant from TAP Pharmaceuticals
Scholten et al., 2003217 patients at multiple centers, mean age 53 (sd ~14); 99% whiteGrade B: 73%
Grade C: 27%
(LA Classification)
217 enrolled; number screened, eligible not reported.Not evaluatedNot evaluatedpantoprazole 40 mg vs esomeprazole 40 mg
No or only mild heartburn:
99% vs 98%
Not evaluatedNot reported (all patients were Grade B or C)3 patients discontinued due to adverse events not related to study drug (myocardial infarction, headache, allergic reaction). Groups not reported.Fair: ITT results not reported, randomization and allocation concealment methods not reported.Supported by a grant from ALTANA
Pharma AG, Germany.

From: Evidence Tables

Cover of Drug Class Review: Proton Pump Inhibitors
Drug Class Review: Proton Pump Inhibitors: Final Report Update 5 [Internet].
McDonagh MS, Carson S, Thakurta S.
Portland (OR): Oregon Health & Science University; 2009 May.
Copyright © 2009, Oregon Health & Science University, Portland, Oregon.

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