Evidence Table 7

Randomized controlled trials of duodenal ulcer treatment: Proton pump inhibitor compared with proton pump inhibitor

Author
Year
Setting
Age, Gender, Race
Other Population
Characteristics
InterventionControlNumberOutcomes Reported (Results)Number of Adverse EffectsQuality Rating
Beker
1995
Multicenter
Median age 44 (range 20 - 86)
70% male
50% smokers
20% alcohol users
58% 2 or more previous ulcers
Pantoprazole 40 mg once daily x 2 to 4 weeksOmeprazole 20 mg once daily x 2 to 4 weeks group)270 enrolled (135 eachHealing:
(PP analysis)
2 weeks: 71% pantoprazole, 65% omeprazole (p=0.31)
4 weeks: 95% pantoprazole, 89% omeprazole (p= 0.09)
ITT analysis results reported as ‘similar’
Symptoms:
Pain free (of those with pain at baseline)
2 weeks: 81% pantoprazole, 82% omeprazole (p = 0.87)
Patient diary: no significant differences in time course of becoming pain free.
21 patients reported adverse events (10 pantoprazole, 11 omeprazole), with a total of 23 events reported. Diarrhea was the most common adverse event reported. 5 were considered serious (1 pantoprazole, 4 omeprazole). 3 in the omeprazole group were considered possibly related to study treatment (1 angina pectoris, 1 hypertension, 1 vertigo) and patients were withdrawn from study. The other 2 were GI hemorrhage pantoprazole, and abdominal pain omeprazole and considered not related to study drugs. No clinically significant changes in lab values from baseline values.
Serum gastrin levels rose in both groups at both 2 and 4 weeks, the change was statistically significant within but not between groups.
Fair
Capurso
1995
Italy
Multicenter
Reported as ‘balanced’ for age, sex, weight, smokers, alcohol use, ulcer history, symptoms, ulcer size, and prior complicationsLansoprazole 30 mg a day (morning) x 2 to6 weeksOmeprazole 20 mg once daily x 2 to 6 weeks107 enrolled, (52 lansoprazole, 55 omeprazole)Healing rates:
2 weeks: 58% lansoprazole, 57% omeprazole
4 weeks: 94% lansoprazole, 94% omeprazole
Nighttime pain free:
2 weeks: 94% l), 87% omeprazole (NS)
Daytime Pain free
2 weeks: 92% lansoprazole, 81% omeprazole (NS)
8 adverse effects reported: 3 rabeprazole, 3 lansoprazole, and 2 omeprazole. No biochemistry abnormalities, no significant difference between therapies for changes in gastrin levels or changes in endocrine cells from biopsiesFair
Chang
1995
Taiwan
Single center
Mean age 57 and 61
89% male
47% smokers
93% H. pylori positive
Lansoprazole 30 mg once daily x 4 weeksOmeprazole 20 mg once daily x 4 weeks83 enrolled (42 lansoprazole, 41 omeprazole)Healing:
4 weeks: 95.2% lansoprazole, 92.7% omeprazole
H. Pylori eradication:
4 weeks: 78.9% lansoprazole, 82.1% omeprazole
Serum PGA was elevated in both groups (NS), and had returned to baseline at 8 weeks. In both groups, the elevation in PGA was significantly higher in those found to have H. pylori eradication (of those H. pylori positive)Fair
Chang
1995
Taiwan
single center (from abstract only – full text not available for this draft)
Not availableLansoprazole 30 mg once daily x 4 weeksOmeprazole 20 mg once daily x 4 weeks111 enrolled (57 lansoprazole, 54 omeprazole)Healing:
4 weeks:
(ITT) 89.5% lansoprazole, 83% omeprazole
(PP) 96% lansoprazole, 94% omeprazole
Hypergastrinemia in both groups (approximately 1.6 fold increase)
Skin rash and constipation occurred in a few cases (groups not specified)
Not assessed
Dekkers
1999
Belgium, England,
Germany
Multicenter
Mean age 48 (range 20- 77)
65% male
51% smokers
54% alcohol users
83% H. pylori positive
Rabeprazole 20 mg once daily. Duration not clearly stated, but assumed to be 4 weeks based on outcome measure timingOmeprazole 20 mg a day x 4 weeks (Duration not clearly stated, but assumed to be 4 weeks based on outcome measure timing)205 enrolled (102 rabeprazole, 103 omeprazole)Healing rates (ITT):
2 weeks: 69% rabeprazole, 63% omeprazole
4 weeks: 99% rabeprazole, 96% omeprazole
Pain frequency: all patients showed improvement (no statistical difference found)
Pain severity: All patients reported improvement in both daytime and nighttime pain. The only statistically significant difference was found in daytime pain at 4 weeks (92% vs 83% improved, rabeprazole vs omeprazole, p = 0.038). No difference found in the number pain free.
43 patients reported at least on adverse event. (21 headache. The mean elevations in serum gastrin levels at 4 weeks were 39.8 pg/ml rabeprazole and 18.9 pg/ml omeprazole.Fair
Dobrilla
1999
Italy
Multicenter
Mean age 45 (range 18 - 69)
66% male
52% smokers
34% alcohol use
90% Helicobacter pylori positive
Lansoprazole 30 mg once a day x 4 weeks, then those with healed ulcer randomized to 15 or 30 mg lansoprazole daily x 12 monthsOmeprazole 40 mg once a day, then those with healed ulcer switched to omeprazole 20 mg daily x 12 months251 eligible (167 lansoprazole, 84 omeprazole), unclear number found H. pylori positive who decided not to participate. Maintenance phase: 243 enrolled (164 lansoprazole, 79 omeprazole)Healing:
4 weeks:
(unclear analysis, only 243 of 251 included)
93.9% lansoprazole, 97.5% omeprazole
PP analysis (# not reported):
4 weeks: 99% lansoprazole, 100% omeprazole
Symptoms:
No pain at 4 weeks:
87.9% lansoprazole, 87.4% omeprazole
Maintenance: (unclear analysis)
6 months: 4.5% lansoprazole 15 mg, 0% lansoprazole 30 mg, 6.3%
omeprazole relapse
12 months: 3.3% lansoprazole 15 mg, 0% lansoprazole 30 mg,
3.5% omeprazole
PP analysis:
6 months: 0% relapse in all groups
12 months: 1.9% lansoprazole 15 mg, 0% lansoprazole 30 mg, 3.6% omeprazole relapse
Followup (at 18 months):
27.3% lansoprazole 15 mg, 20% lansoprazole 30 mg, 26.7% omeprazole relapse
16 during phase I (4 weeks), 10 (6%, lansoprazole), 6 (7.1%, omeprazole) Phase 2 (maintenance): 9 (12.2%, lansoprazole 15 mg), 4 (5.6%, lansoprazole 30 mg), and 8 (11%, omeprazole). The most common adverse event was diarrhea. 8 patients withdrew due to adverse events (3 lansoprazole 15 mg, 2 lansoprazole 30 mg, 3 omeprazole) including diarrhea, rash, gynecomastia, asthenia, precordial pain, fever, and weight gain. No significant changes in laboratory tests were found. Serum gastrin levels were elevated in both groups at 4 weeks (increase of 23.8pg/ml lansoprazole 30 mg, 35.8pg/ml omeprazole; NS), and continued to be elevated at 6 and 12 months of maintenance therapy. The lansoprazole 15 mg group had the least and the lansoprazole 30 mg group had the highest elevation at 6 and 12 months. At 6 months followup all values were returning to baseline.Fair-poor
Ekstrom
1995
Sweden
Multicenter
Mean age 55
47% smokers
43% alcohol users
10% NSAID users
Lansoprazole 30 mg once a day x 4 weeksOmeprazole 20 mg a day x 4 weeks279 enrolled (143 lansoprazole, 136 omeprazole)Healing rates:
2 weeks:
Endo: 86.2% lansoprazole, 82.1% omeprazole
PPl: 87.9% lansoprazole, 82.3 omeprazole
4 weeks:
Endo: 97.1% lansoprazole, 96.2% omeprazole
PPl: 97.7% lansoprazole, 96/7% omeprazole
Symptoms:
Most patient’s symptoms improved to ‘occasional’ or ‘none’ by two weeks, nearly all by 4 weeks in both groups. At 4 weeks the reduction in symptoms favored lansoprazole, p = 0.041 (98% vs 96% with more than occasional symptoms).
Antacids: no difference found
68 adverse events occurred in 57 patients (23 patients taking lansoprazole, 34 taking omeprazole). No statistically significant difference in the severity was found between the two groups. A statistically significant difference was found in the mean change in ALAT concentration, but the change was minor (0.05 unit increase lansoprazole, 0.03 unit decrease omeprazole).Fair
Fanti
2001
Italy
Single center
Median age 47
lansoprazole and 48 omeprazole
68% male
56% smokers
54% alcohol users
Lansoprazole 30 mg once a day x 4 weeks
Plus clarithromycin
500 and tinidazole 1 gm x 7 days
Omeprazole 20 mg a day x 4 weeks
Plus clarithromycin 500 and tinidazole 1 gm x 7 days
43 enrolled (22 lansoprazole and 21 omeprazole)Healing rates:
8 weeks: 100% both groups
Symptoms: ”rapid clinical response with disappearance of symptoms in both groups”
“Mild and self-limiting” Total number not reported 1 lansoprazole stomatitis and 1 omeprazole mild diarrheaFair
Ji
2006
Wonju Christian
Hospital - South Korea
Mean age 50.7
71.4% male
Race NR
BMI 22.8
Tobacco use 59.8%
Alcohol use 55.4%
75.9% H. pylori positive
Rabeprazole 10 mg once daily in the morning for 6 weeksOmeprazole 20 mg once daily in the morning for 6 weeks112 randomized (56 in each group)Remaining ratio of peptic ulcers after 1 week
Rabeprazole 45.5% omeprazole 50.3% p = 0.475
Healing rates at 6 weeks
(ITT) rabeprazole 80.6% omeprazole 87.0% p = 0.423
Proportions with daytime symptom resolution at week 6
Rabeprazole 63.6% omeprazole 64.3% p = 0.958
Proportions with night-time symptom resolution at week 6
Rabeprazole 72.4% omeprazole 73.1% p = 0.956
Three non-serious adverse events in the omeprazole group (2 headache and 1 nausea), and no adverse event in the rabeprazole groupFair- no methods reported on randomization or blinding and endoscopy was not done on all so analysis is actually a completers analysis for ulcer healing
Subei
2007
Multicenter and multinational
Mean age (SD) 40.7 (13.1)
65.2% male
32.4% white, 16.6% black, 5.3% Asian, 45.7% other 100% H. pylori positive
Esomeprazole, 20 mg bid, amoxicillin, 1000 mg bid, and clarithromycin, 500 mg bid (EAC), triple therapy, given for 1 week and followed by 3 weeks of placebo,Omeprazole 20 mg bid, amoxicillin, 1000 mg bid, and clarithromycin, 500 mg bid (OAC), triple therapy, given for 1 week and followed by 3 weeks of omeprazole, 20 mg od, monotherapy382 randomized - 374 ITT (186 esomeprazole 188 omeprazole)Healing rates at 4 weeks
(ITT) 73.7% esomeprazole, 76.1% omeprazole
95% CI −11.2% to 6.4%
(PP) 76.7% esomeprazole
81.3% omeprazole

Healing rates at 8 weeks
(ITT) 86.6% esomeprazole, 88.3% omeprazole
(PP) 92.0% esomeprazole, 94.2% omeprazole

H. pylori eradication at 8 weeks:
(ITT) 74.7% esomeprazole, 78.7% omeprazole 95% CI 72.2–84.3
(PP) 84% esomeprazole, 86.2% omeprazole 95% CI 79.0–91.6
Esomeprazole vs.. Omeprazole
Dysgeusia 17 (9.0%) vs.. 23 (11.9%)
Diarrhea 16 (8.5%) vs.. 15 (7.8%)
Headache 9 (4.8%) vs..14 (7.3%)
Abdominal pain 7 (3.7%) vs..4 (2.1%)
Nausea 5 (2.6%) vs.. 7 (3.6%)
Fair
Tulassay
2001
Hungary, Poland, Czech Republic Multicenter
Mean age 46 (SD 13)
62% male
100% white
57% smokers
all were H. pylori positive
Esomeprazole 20 mg twice daily plus clarithromycin 500 mg and amoxicillin 1 gm twice daily × 1 week, placebo × 3 weeksOmeprazole 20 mg twice daily mg × 4 weeks plus clarithromycin 500 mg and amoxicillin 1 gm twice daily × 1 week446 randomized (222 esomeprazole 224 omeprazole)Healing rates:
4–6 weeks:
(ITT) 91% esomeprazole, 92% omeprazole
(PP) 94% esomeprazole, 96% omeprazole
H. pylori eradication:
(ITT) 86% esomeprazole, 88% omeprazole
(PP) 89% esomeprazole, 90% omeprazole
(NS)
33% of esomeprazole and 29.5% of omeprazole reported at least one adverse event. Most frequent taste perversion, diarrhea, loose stools. 4 discontinued for adverse events (e: 1 for taste perversion/vomiting, o: 1 for rash, 1 allergic reaction, 1 dysmenorrhea). No clinically relevant trends for changes in laboratory safety variables.Fair

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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