Comparable Efficacy of Pantoprazole and Omeprazole ... - Zdravie.sk

Original Paper: Esophageal Disorders 

Digestion 2003;67:6–13 

DOI: 10.1159/000070201 

Comparable Efficacy of Pantoprazole and 

Omeprazole in Patients with Moderate to Severe 

Reflux Esophagitis 

Results of a Multinational Study 

T. Körner a K. Schütze b R.J.M. van Leendert c I. Fumagalli d 

B. Costa Neves e M. Bohuschke f G. Gatz f 

a Zentralklinikum Suhl gGmbH, Suhl, Germany; b Hanusch-Krankenhaus, Vienna, Austria; 

c Albert Schweitzer Ziekenhuis, Zwijndrecht, The Netherlands; d Medical Centre, Locarno, Switzerland; 

e Hospital de Pulido, Lisbon, Portugal; f ALTANA Pharma AG, Konstanz, Germany 

Key Words 

Acid-related Disease W Esophagitis W Gastroesophageal 

reflux disease W Omeprazole W Pantoprazole W Proton 

pump inhibitor 

Abstract 

Aim: To compare the efficacy and tolerability of pantoprazole 

40 mg and omeprazole MUPS 40 mg in patients 

with moderate to severe gastroesophageal reflux disease 

(GERD). Methods: In this randomized, double-blind, 

parallel-group, multicenter study conducted in Austria, 

Germany, Portugal, Switzerland and The Netherlands, 

patients with endoscopically confirmed moderate to severe 

GERD (Savary/Miller esophagitis grade II/III) were 

enrolled. They received a once-daily dose of either 40 mg 

pantoprazole or 40 mg omeprazole MUPS. Healing was 

determined by endoscopy after 4 weeks of treatment. If 

patients were not healed, treatment was extended for 

another 4 weeks. An additional endoscopy was performed 

in these cases after 8 weeks of treatment. Healing 

was determined by endoscopy after 4 and 8 weeks. In 

addition, treatment effect on symptoms was evaluated 

by the investigator using a questionnaire assessing 

heartburn, reflux regurgitation and pain on swallowing 

at each visit, as well as by a self-administered question- 

ABC 

Fax + 41 61 306 12 34 

E-Mail karger@karger.ch 

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© 2003 S. Karger AG, Basel 

0012–2823/03/0672–0006$19.50/0 

Accessible online at: 

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Received: August 26, 2002 

Accepted: February 20, 2003 

naire comprising further 24 gastrointestinal symptoms. 

Analyses were performed for the intention-to-treat (ITT) 

and the per-protocol (PP) population. In addition, patients 

with high compliance (HC: 90% ^110%) were considered 

in a separate group. Adverse events and the 

influence of the Helicobacter pylori status were investigated. 

Results: A total of 669 outpatients were enrolled in 

the study, with 337 patients receiving pantoprazole and 

332 omeprazole MUPS. The PP population consisted of 

552 patients, 282 treated with pantoprazole and 270 with 

omeprazole MUPS. The healing rates in both treatment 

groups were shown to be equivalent and were higher in 

patients who adhered closely to the administration protocol 

(HC). According to ITT (ITTHC) analyses, healing 

rates were 65.3% (77.4%) in the pantoprazole and 66.3% 

(74.7%) in the omeprazole group after 4 weeks. Furthermore, 

patients infected with H. pylori had slightly but not 

significantly higher healing rates than those with a negative 

test result. The safety profile of both treatments was 

comparable. Conclusion: Pantoprazole 40 mg and omeprazole 

MUPS 40 mg were equivalent with respect to 

healing after 4 and 8 weeks of treatment in patients with 

reflux esophagitis grade II/III. Overall, HC patients had 

higher healing rates than the regular compliant patients. 

Both drugs were well tolerated and safe. 

Copyright © 2003 S. Karger AG, Basel 

PD Dr. Thomas Körner 

Zentralklinikum Suhl gGmbH 

Albert-Schweitzer-Strasse 2 

D–98527 Suhl (Germany) 

Tel. +49 3681 355440, Fax +49 3681 355441, E-Mail thomas.koerner@zs.srh.de

Introduction 

Gastroesophageal reflux disease (GERD) is widely 

spread and has a great impact on patients’ quality of life 

[1, 2]. In the Western population, approximately 7% of all 

patients consulting a physician because of gastrointestinal 

complaints are suffering from heartburn [3]. The therapeutically 

most easily influenced pathogenetic factor in 

the development of GERD and its complications is gastric 

acid. Control of gastric acid secretion is the major key 

factor in healing the disease and numerous studies demonstrated 

the close correlation between the extent of acid 

secretion and therapeutic success [3, 4]. In most cases proton 

pump inhibitors (PPIs) achieve the desired acid suppression 

when given once daily, they are widely accepted 

to be the best treatment option. It is generally accepted 

that PPIs are significantly superior to H2-receptor antagonists 

[5–8], prokinetics [9] and placebo [for review see 10– 

12]. Further, it was previously shown that pantoprazole 

and omeprazole are highly efficacious in the treatment of 

mild [13] and moderate to severe GERD [14, 15]. However, 

a direct comparison of equal doses of pantoprazole 

and omeprazole in patients with moderate to severe 

GERD has not been performed so far. 

Dose-finding studies and comparative trials demonstrated 

pantoprazole 40 mg to be the optimal dose for the 

treatment of moderate to severe reflux esophagitis and 

20 mg for mild disease [16–18]. For omeprazole a standard 

dose of 20 mg has been recommended for the treatment 

of GERD, but in practice 40 mg are often used [19, 

20]. Our aim was to directly compare the once-daily dose 

of pantoprazole 40 mg with omeprazole MUPS 40 mg in 

the treatment of reflux esophagitis grade II and III as 

defined by Savary and Miller [21]. Outcome criteria were 

the efficacy and tolerability of both drugs with regard to 

endoscopically proven healing and symptom relief after 4 

and 8 weeks of treatment and a possible effect of the bacterium 

Helicobacter pylori on treatment outcome. 

Patients and Methods 

Design and Ethical Considerations 

This study was conducted as a randomized, double-blind, multicenter, 

parallel-group study involving 5 centers in Austria, 53 in Germany, 

3 in Portugal, 12 in Switzerland and 8 in The Netherlands. 

The study was conducted according to good clinical practice and the 

Declaration of Helsinki. Furthermore, independent local ethics committees 

in the respective countries approved the protocol and all 

patients gave their written informed consent prior to participation. 


Omeprazole in Reflux Esophagitis 

Patient Populations 

A total of 669 male and female patients, aged 618 years (for Austria 

619 years, 1 patient was ! 18 years for whom the parents gave 

their written consent), were enrolled in this study between May 2000 

and February 2001. They had endoscopically confirmed reflux 

esophagitis grade II or III (Savary/Miller classification) and had suffered 

from at least moderate heartburn during the 3 days prior to 

inclusion (for grading of symptoms see Medical Assessment below) 

[21]. Main exclusion criteria were the following: any other gastrointestinal 

disease, i.e. GERD grades other than II or III, florid peptic 

ulcer, history of Zollinger-Ellison syndrome, pyloric stenosis, esophageal 

or gastric surgery, and severe diseases of other body systems. 

Patients were excluded if they took PPIs, H2-receptor antagonists, 

prokinetics for more than 10 days, systemic glucocorticosteroids, 

anti-inflammatory drugs for more than 3 consecutive days or had 

had PPI-based tribple therapy during the previous 28 days. 

Intake of sucralfate during the 3 days prior to study start also led 

to exclusion. Regular intake of acetyl salicylic acid of dosages up to 

150 mg/day was allowed. 

Treatment and Conduct 

Patients were randomized to one of two treatment groups receiving 

either 40 mg pantoprazole or 40 mg omeprazole MUPS once daily. 

Randomization was performed by means of a computer-generated 

randomization list. Patients received their patient number in ascending 

order corresponding to the order of inclusion. This number corresponded 

to a randomized medication. Treatment was extended to 8 

weeks for patients not healed after 4 weeks. 

For blinding purposes, both pantoprazole and omeprazole tablets 

were encapsulated. Encapsulation did not change the dissolving or 

absorption properties of the omeprazole MUPS formulation [22]. 

At study start patients were assessed endoscopically to determine 

the grade of GERD. The presence of H. pylori was proven directly 

after the endoscopy at the initial examination by means of a standardized 

and validated, commercially available H. pylory rapid urease 

test (RUT; CLOtest ® , Ballard Medical Products, USA) kit. For 

this test, at least 1 biopsy specimen from the antrum and 1 from the 

corpus were taken. A patient was considered H. pylori-negative if the 

result was negative from both parts of the stomach. The investigator 

questioned patients about leading symptoms (heartburn, acid eructation, 

pain on swallowing), medical history, concomitant medication 

and clinical symptoms. A physical examination was performed and a 

blood sample was taken for standard laboratory investigation. Two 

weeks after the initial examination a first follow-up visit was carried 

out, at which the investigator assessed symptoms and patients filled 

in a symptom questionnaire. Further follow-up visits were scheduled 

after 4 and, if necessary, 8 weeks of treatment. Endoscopies were performed 

at baseline, after 4 and, if necessary, 8 weeks of treatment to 

ascertain the extent of healing. 

During the initial endoscopy 1 biopsy each was taken from the 

antrum and from the corpus for H. pylori testing. Concomitant medication 

and adverse events were documented at each follow-up visit. 

Compliance was checked by counting returned tablets. Patients were 

considered non-compliant if they took less than 80% of the medication. 

Patients were considered to be highly compliant (HC) if they 

took between 90 and 110% of the study medication, i.e. if they strictly 

adhered to the administration instructions. 

Digestion 2003;67:6–13 7

Medical Assessment 

Endoscopy. Healing was defined as complete epithelialization of 

the lesions as confirmed by endoscopy. Healing rates were determined 

after 4 and 8 weeks of treatment for both treatment groups. 

Leading Symptoms. The presence and intensity of the leading 

symptoms of reflux heartburn, acid regurgitation and pain on swallowing, 

were assessed at each visit and documented as either mild, 

moderate or severe by the investigator on a 4-point scale (from 0 = 

absent to 3 = severe). A patient with at least mild symptoms at baseline 

was defined symptom-free if no symptoms were reported at the 

respective visit. 

GI Symptoms. In addition to the symptom questioning by the 

investigator, patients were requested to fill in a self-administered 

questionnaire about further 24 GI symptoms. Frequency and intensity 

of each symptom were assessed on a 6-point scale (from 0 = not at 

all to 5 = every day and 0 = absent to 5 = very severe, respectively). 

For each patient a sum score was calculated as the sum of frequency 

! intensity/(5 ! 5), divided by the number of reported symptoms in 

order to normalize the sum score values to the range 0–1. 

In addition, a factor analysis of the self-reported gastrointestinal 

(GI) symptoms was carried out in order to identify a symptom pattern 

in moderate to severe esophagitis. The parameters severity, frequency, 

and symptom load (frequency ! severity) were analyzed by 

use of VARIMAX. Items to be retained in the groups required item 

loadings of 10.4. Groups comprised items with the largest load on 

one factor, since for several items multiple assignments to different 

factors were seen. 

Safety 

At every follow-up visit patients were asked about occurrence of 

adverse events. The investigator assessed the causal relationship of 

the event to the intake of the study medication as either unrelated, 

unlikely, likely, or definitely related. 

Statistical Analysis 

The sample size evaluation was performed on the basis of healing 

rates after 4 weeks of treatment. A difference of 15% between both 

treatment groups was considered as clinically relevant. Two hundred 

and fifty-six patients per group were required to detect this difference 

on a 5% level of significance and a power of 80%. 

The primary efficacy variable was the endoscopically confirmed 

healing after 4 weeks. Healing rates were calculated for both groups 

and compared. The null hypothesis of this study, that there is no 

difference between the drugs, was tested by Cochran-Mantel/Haenszel 

method on a 5% level. The 95% confidence intervals (CIs) were 

calculated for the odds ratios. Equivalence was concluded if the 95% 

CIs were completely within the interval 0.33–3. Secondary criteria 

were healing rates after 8 weeks and symptom relief rates concerning 

the 3 leading symptoms and the other GI symptoms after 2, 4 and 8 

weeks. Symptom relief rates of the leading symptoms were only evaluated 

descriptively. The pre- and posttreatment differences between 

GI symptoms baseline values and those after 2, 4 and 8 weeks were 

calculated for the sum score of the GI leading symptoms as well as for 

the sum score of the self-assessed GI symptoms as measured by the 

patient questionnaire. The obtained values of both treatment groups 

were compared two-sided on a 5% level using the Wilcoxon ranksum 

test. In addition, the main parameter was evaluated taking the 

H. pylori status into account. Furthermore, the correlation between 

endoscopic and symptomatic healing was calculated by means of 

Cramer’s V. 

Table 1. Demography and medical history (ITT) 

Patient 

characteristics 

Pantoprazole 

40 mg 

(n = 337) 

Omeprazole 

MUPS, 40 mg 

(n = 332) 

Age, years B SD 53.7B14.3 53.8B14.6 

Height, cm B SD 171.7B8.7 170.4B9.3 

Weight, kg B SD 78.9B13.7 78.0B14.4 

Body mass index, kg/m 2 B SD 26.8B4.0 26.8B4.2 

Men/women 216/121 186/146 

Non-smokers, n (%) 264 (78.3) 253 (76.2) 

Alcohol consumers, n (%) 23 (6.8) 22 (6.6) 

Esophagitis grade II, n (%) 283 (84.0) 281 (84.6) 

Esophagitis grade III, n (%) 54 (16.0) 51 (15.4) 

H. pylori positive, n (%) 72/337 (21.4) 82/332 (24.7) 

H. pylori negative, n (%) 257/337 (76.3) 241/332 (72.6) 

Dichotomous parameters were compared by Fisher’s exact twotailed 

test and ordinal variables by the Wilcoxon rank-sum test. 

Populations 

Protocol violators were defined before unblinding. The statistical 

analyses of the primary and secondary parameters were performed 

by intention-to-treat (ITT) and per-protocol (PP) analysis. Symptoms 

assessed by the patient questionnaire were analyzed only PP. 

The ITT population comprised all patients included. The PP analysis 

excluded protocol violators. In addition, all parameters were analyzed 

in subgroups comprising HC patients, i.e. patients that took 

between 90 and 110% of the study medication and therefore adhered 

closely to the administration protocol (ITTHC and PPHC). 

Results 

Study Populations 

Overall, 669 patients were included in the study (ITT 

population). All patients who completed the study without 

protocol violations were included in the PP population, 

which comprised 552 patients, 282 in the pantoprazole 

and 270 in the omeprazole MUPS group. The most 

prominent protocol violations were violation of the inclusion 

criteria, poor compliance, intake of not permitted 

concomitant medication, or deviations from the first follow-up 

visit dates. The subgroup of HC patients within 

the PP population comprised 452 patients, 233 in the 

pantoprazole and 219 in the omeprazole MUPS group. 

The populations are described in figure 1. 

No clinically relevant differences in the demographic 

characteristics between the treatment groups were observed 

(table 1). The ratios of H. pylori-positive and 

-negative patients as well as the percentage of patients 

8 Digestion 2003;67:6–13 Körner/Schütze/van Leendert/Fumagalli/ 

Costa Neves/Bohuschke/Gatz

Fig. 1. Study populations and patient flowchart. 

Table 2. Comparison between treatment groups 

Population Odds ratio 95% CI 

4 weeks ITT 0.957 0.696–1.318 

ITTHC 

1.1620.759–1.718 

PP 0.921 0.636–1.334 

PPHC 1.111 0.718–1.720 

8 weeks ITT 0.950 0.624–1.446 

ITTHC 1.148 0.541–2.436 

PP 0.814 0.435–1.523 

PPHC 1.068 0.469–2.430 

Equivalence was concluded if the 95% CI ranged between 0.33 

and 3. 

with reflux esophagitis grade II or III were similar in both 

groups. At baseline, reflux esophagitis grade II was diagnosed 

in 85.0% of patients in the PP population (242 

patient in the pantoprazole, 227 in the omeprazole MUPS 

group), and grade III in 15.0% of patients. 

Efficacy 

The primary parameter was endoscopically confirmed 

healing of the esophageal lesions after 4 weeks of treat- 



Fig. 2. Healing rates of GERD grade II/III after 4 and 8 weeks of 

treatment with 40 mg pantoprazole or 40 mg omeprazole MUPS. 

ment. After this first treatment period healing rates were 

similar for both drugs and statistically equivalent for all 

populations (table 2, fig. 2). Overall, 70.9% of patients 

were healed in the pantoprazole and 72.6% of patients in 

the omeprazole MUPS group after 4 weeks of treatment 

(PP). The healing rates after 8 weeks of treatment were 

also similar in both treatment groups. Only a few patients 

in both groups remained unhealed, but in most of them 

the reflux esophagitis improved to grade I. As expected, in 

all subgroups comprising HC patients, healing rates were 

higher than in patients with regular compliance, with 

slightly but not significantly higher values in the pantoprazole 

than in the omeprazole MUPS group for ITT and 

PP populations both after 4 and 8 weeks of treatment (table 

3; p 1 0.05). 

Influence of the H. pylori Status on Esophagitis Healing. 

Additionally, the influence of the H. pylori status on 

treatment outcome was examined. H. pylori was present 

Digestion 2003;67:6–13 9

Table 3. Healing rates (%) of reflux esophagitis in HC patients after 

4 and 8 weeks of treatment with pantoprazole or omeprazole MUPS 

once daily 

Pantoprazole 40 mg 

ITTHC 

PPHC 

Omeprazole MUPS 40 mg 

ITTHC 

PPHC 

4 weeks 77.4 77.7 74.7 75.8 

8 weeks 94.1 94.8 93.3 94.5 

Table 4. Symptom relief rates (%) after 2, 4 and 8 weeks of treatment 

with pantoprazole and omeprazole MUPS in the PP population 

Pantoprazole Omeprazole MUPS 

2 weeks 

Heartburn 70.274.4 

Acid eructation 73.7 75.6 

Pain on swallowing 74.3 74.1 

4 weeks 

Heartburn 83.7 88.1 



8 weeks 




Table 5. Symptom sum score values of leading GI symptoms after 2, 

4 and 8 weeks in the PP population 

Symptom sum score Pantoprazole Omeprazole MUPS 

Baseline 5.04B1.825.12B2.01 

2 Weeks 0.80B1.420.75B1.35 

4 Weeks 0.44B0.94 0.28B0.81 

8 Weeks 0.33B0.78 0.24B0.71 

Table 6. Correlation between endoscopic healing and symptom 

relief after 4 weeks of treatment in the ITT population (n = 669) 

Endoscopically healed but 

no symptom relief (%) 

after 4 weeks after 8 weeks 




in 22.8% of PP patients at baseline as tested by RUT. It 

could be shown that the overall healing rates after 4 weeks 

of treatment in patients infected with H. pylori were higher 

(ITT: 68.2%, PP: 77.0%) than in those with a negative 

H. pylori test result (ITT: 65.3%, PP: 70.3%). However, 

this difference did not reach statistical significance (p 1 

0.05). After 8 weeks of treatment the effect of H. pylori on 

healing was less prominent and patients had similar healing 

rates, irrespective whether they were H. pylori positive 

(ITT: 85.1%, PP: 93.7%) or negative (ITT: 85.0%, PP: 

92.2%). Therefore, H. pylori status did not influence the 

healing of esophageal lesions in this study. 

Symptom Relief. After 2 weeks of treatment, relief of 

all 3 symptoms (complete absence of heartburn, acid eructation, 

and pain on swallowing) was achieved in more 

than 70% of patients in both treatment groups (PP population). 

The relief rates increased during further treatment 

to over 83% after 4 weeks and 89% after 8 weeks in both 

groups (table 4). 

At baseline, the mean symptom sum score of the GI 

leading symptoms was 5.04 in the pantoprazole and 5.12 

in the omeprazole MUPS group (PP population). In both 

groups this score value decreased strongly during treatment 

(to 0.33 in the pantoprazole and to 0.24 in the omeprazole 

MUPS group after 8 weeks, table 5). The differences 

between the treatment groups regarding the sum 

score after 2, 4 and 8 weeks were not statistically significant 

(p 1 0.05). 

In addition, the correlation between endoscopic and 

symptomatic healing was calculated in order to identify 

the proportion of those patients who still had symptoms 

but were healed according to endoscopy (table 6). The 

proportion of patients that were endoscopically healed 

but not symptom-free increased from more than 17.9% 

after 4 weeks to more than 36.7% after 8 weeks of treatment. 

Results were similar for the 2 treatment groups and 

comparison between them did not yield any statistically 

significant difference (p 1 0.05). 

Patient Questionnaire. Patients were asked to fill in a 

patient questionnaire at each visit. Mean sum scores 

decreased from 0.163 and 0.175 at baseline to 0.025 and 

0.033 within 8 weeks in the pantoprazole and omeprazole 

MUPS group, respectively (PP population). Differences 

between treatment groups were not statistically significant 

(p 1 0.05). 

In addition, a factor analysis of the gastrointestinal 

symptoms was performed in order to identify an underlying 

symptom pattern, considering frequency and intensity 

of the reported symptoms. Factor analyses were consistent 

and 5 symptom clusters were isolated: Each cluster 



contains the symptoms that occurred most often together: 

(1) acid-related symptoms (heartburn at day/night, acid 

eructation, burn in throat, burning behind the breastbone, 

dysphagia); (2) upper-epigastric-pain-related symptoms 

(pain, malaise, pressure, cramps, and burn in the epigastrium); 

(3) typical symptoms of irritable bowel syndrome 

(pain, cramps and pressure in the lower abdomen, alternating 

diarrhea and constipation); (4) meteroism-related 

symptoms (feeling of inflation, satiety feeling, uncomfortable 

deflation, bad breath, feeling of incomplete defecation, 

eructation/burping), and (5) vomiting-related symptoms 

(vomiting, retching, nausea). The symptoms with 

the highest correlation coefficient in each cluster were 

(1) heartburn at day; (2) pain in the epigastrium, (3) pain 

in the lower abdomen; (4) feeling of inflation, and 

(5) vomiting. 

Compliance. Compliance was similar in both groups 

for the first treatment period (4 weeks) as well as for the 

second period (further 4 weeks). In the pantoprazole 

group mean compliance was similar with 98.1% for the 

first and 97.7% for the second treatment period; in the 

omeprazole group compliance was 97.1 and 96.2%, respectively. 

The percentage of HC patients, i.e. those who 

took 90–110% of the study medication, were 70.9% (239/ 

337) in the pantoprazole and 67.8% (225/332) in the omeprazole 

MUPS group (ITT). 

Adverse Events 

Safety data were analyzed for the 669 patients of the 

ITT population, 86 patients (13%) reported a total of 128 

adverse events, 40 patients in the pantoprazole and 46 

patients in the omeprazole MUPS group. The most frequently 

reported adverse event in the pantoprazole group 

was headache (1%) and in the omeprazole MUPS group 

diarrhea (2%). However, adverse events were mostly of 

mild (41%) or moderate (50%) intensity. A total of 2.1% 

adverse events (n = 7) in the pantoprazole and 1.2% (n = 

4) in the omeprazole MUPS group were of severe intensity. 

Most of adverse events were considered to be unrelated 

(55%) or unlikely related to the study medication 

(23%); only 2 were thought to be definitely related, headache 

in the pantoprazole and toxicoderma in the omeprazole 

MUPS group. The latter adverse event was of moderate 

intensity and led to premature discontinuation. In the 

entire study 4 serious adverse events were reported, 2 in 

the pantoprazole and 2 in the omeprazole MUPS group, 

but all were judged to be unrelated to the study medication 

by the investigator. Four patients from the pantoprazole 

group and 7 from the omeprazole MUPS group withdrew 

due to adverse events. 



Discussion 

The present study demonstrated pantoprazole 40 mg 

daily to be as effective as omeprazole MUPS 40 mg daily 

with respect to endoscopically proven healing of moderate 

to severe reflux esophagitis and relief of reflux symptom. 

So far, it is one of the largest multicenter studies on 

patients with moderate to severe GERD comparing equal 

doses of both drugs. 

Healing rates of 70.9 and 91.5% were observed after 4 

and 8 weeks, respectively, in the pantoprazole group (PP 

population). The corresponding healing rates in the omeprazole 

MUPS group were 72.6 and 93.0%. Both study 

drugs showed equivalent efficacy in healing the reflux 

esophagitis. There were no significant differences between 

the treatment groups with respect to GI symptom 

relief as assessed by the patient questionnaire. These findings 

are in good agreement with previous findings in 

patients with mild to severe GERD treated with 20 mg 

pantoprazole or 20 mg omeprazole MUPS [13]. The correlation 

between endoscopical healing and symptom relief 

was found to be rather low. The proportion of patients 

that were endoscopically healed but not symptom-free 

was 117.9% after 4 weeks and increased to 136.7% after 

8 weeks of treatment. This finding, that endoscopically 

healed patients still suffer from symptoms or vice versa 

(patients with symptoms do not necessarily have a positive 

endoscopic result) is well known and is currently 

under discussion. Thus, the Genval Workshop Report 

states that there is no positive predictive value of GERD 

symptoms (especially heartburn) for erosion [23]. 

The factor analysis of the self-reported GI symptom 

questionnaire supports the previous findings that GERD 

is a disease with a heterogeneous symptom pattern, not 

only to be defined by the presence or absence of so-called 

predominant symptoms [24, 25]. Clinical studies indicate 

that multiple dimensions of symptoms are important in 

the assessment of GERD rather than the assessment of 

predominant symptoms. However, only limited valid information 

exist on coexisting symptoms as a definition 

for GERD. 

It seems obvious that patient compliance has a strong 

influence on treatment effect. However, there are only few 

compliance studies found in the literature focusing on this 

parameter [26–28]. This is surprising, given that adherence 

to the recommended tablet intake (i.e. 100% intake) 

is a prerequisite for the healing process. Therefore, in this 

study, we additionally analyzed the subgroup of patients 

considered to be HC. Healing rates in the HC subgroup 

were 77.7% in the pantoprazole and 75.8% in the omepra- 

Digestion 2003;67:6–13 11

zole MUPS group after 4 weeks (PPHC). This increased to 

more than 94.0% in both treatment groups after a further 

4 weeks of treatment. Furthermore, the healing rates in 

the HC patient group were higher than those in the regular 

compliant patient group. We suggest that for the efficacy 

assessment of a given treatment, stronger emphasis 

should be put on the patient compliance. Compliance 

regarding tablet intake as determined in the protocol has 

an obvious effect on healing rates in moderate to severe 

reflux esophagitis. 

Infection with H. pylori is prevalent in patients with 

GERD, even though it does not appear to play an important 

role in the pathophysiology of the disease. However, 

the relevance of H. pylori for the management of GERD is 

being hotly debated. Some authors found that proton 

pump inhibitors (PPIs) were less effective in H. pylorinegative 

patients – a reason not to eradicate H. pylori in 

GERD patients. Other authors, by contrast, suggested 

that long-term PPI treatment of GERD may lead to atrophic 

gastritis and intestinal metaplasia in H. pylori-positive 

patients and increase the risk of developing gastric 

cancer – a reason to eradicate H. pylori [29, 30]. Numerous 

reviews also have discussed this topic [31–33]. In the 

present study H. pylori was present in 22.8% of PP 

patients at baseline. Infected patients had slightly higher 

healing rates than those with a negative test result. Hence, 

our data support previous findings that H. pylori infection 

seems to interfere with the acid-suppressive effects of 

PPIs [34]. However, the difference in treatment effect 

between H. pylori-infected and -uninfected patients did 

not reach statistical significance, and after further 4 weeks 

of treatment this difference even disappeared. However, 

bearing in mind that high, 40-mg dosages of both PPIs 

were used in this study, it is well conceivable that no significant 

difference was found since the improved efficacy 

of PPIs in esophagitis healing in H. pylori-positive patients 

is seen most easily with lower doses of PPIs [35]. 

The explanation for this finding is still lacking, and the 

potential benefit of retaining the H. pylori-infection is 

questionable considering the inflammatory activity of the 

bacterium in the mucosa and the acceleration of gastric 

atrophy caused by H. pylori infection. However, from the 

experience gained in this study, we suggest that eradication 

still appears advisable. 

Both study drugs were well tolerated, with only 1 

patient in each treatment group reporting adverse events 

that were considered to have a definite causal relationship 

to the study medication. 

Conclusion 

Pantoprazole and omeprazole MUPS were shown to 

be equivalent with respect to healing after 4 and 8 weeks 

of treatment in patients with reflux esophagitis grade II/ 

III. There were also no significant differences between 

both study drugs regarding symptom relief. In summary, 

40 mg pantoprazole o.d. is as effective as 40 mg omeprazole 

MUPS o.d. in the treatment of moderate to severe 

GERD and associated GI symptoms. 

Acknowledgements 

This study was supported by a grant from ALTANA Pharma AG, 

Konstanz, Germany. We would like to thank Dr. Spranger and Dr. 

Weichsel, Ingolstadt, Germany, Dr. Echevarne, Barcelona, Spain, 

and Dr. Viollier, Basel, Switzerland, for performing the laboratory 

investigations. The investigators are very grateful to IFE Institute for 

Research and Development, Witten, Germany, who was responsible 

for monitoring at the study sites, data collection, source data verification 

and biometrical analysis. Many thanks also to Dr. Birgit Köhne 

for preparing the manuscript. To all investigators collaborating in the 

study we express our gratitude (alphabetical order). 

Austria: B. Dragosics (Wien), P. Kratochvil (Graz), T. Stupnicki 

(Deutschlandsberg), H. Wurzer (Graz). 

Germany: A. Achim (Iserlohn), H. Böneke (Lienen), H. Bayer 

(Hamburg), A. Biedermann (Blankenhain), J. Bott (Elmshorn), W. 

Brandt (Potsdam-Babelsberg), G. Bretzke (Zwickau), W. Burmeister 

(Hamburg), H. Daake (Wiesbaden), A. Dettmer (München), A. Dietz 

(Ludwigsfelde), E. Dombrowski (Berlin), H. Eisold (Mössingen), W. 

Elsel (Zwickau), R.-R. Fink (Freising), G.-R. Franke (Dinkelsbühl), 

O. Friedrichs (Duisburg), C. Fritze (Jena), J. Großkopf (Wallerfing), 

B. Hägler (Neufahrn), J. Hein (Marburg), G. Heptner (Dresden), 

K.-H. Hey (Paderborn), J. Hoffschröer (Bad Essen), T. Kammermeier 

(Bogen), S. Kaspari (Lüneburg), H.-U. Kellner (Kassel), R. 

Kern (Rödersheim-Gronau), C. Klein (Künzing), J. Krehbiel (Rödersheim-Gronau), 

H.-G. Krezdorn (München), V. Kroll (Markdorf), 

H. Kubisch (Chemnitz), K.-D. Kurzke (Sulingen), K. Lenz (Isny), 

M. Maaß (Markdorf), W. Marx (Elmshorn), J. Pankow (Flensburg), 

U. Pustlauk (Meinerzhagen), A. Schmidt (Offenbach), J. Schmitz 

(Fürth), G. Scholz (Offenbach), D. Sehland (Rostock), U. Siebert 

(Haßfurt), R. Sievers (Bederkesa), T. Simon (München), K. Teubner 

(Stuttgart), T. Tibroni (Coesfeld), A. Ulmer (Ludwigsburg), R. Vogt 

(Mannheim), C. Völker (München), von Fritsch (Erlangen), R. 

Warncke (Elmshorn), U. Werkmeister (Isny), W. Zink (Nürnberg), 

K. Zöllner (Dippoldiswalde). 

Portugal: J. Fraga (Vila Nova de Gaia), L.A. Novais (Amadora). 

Switzerland: P. Bänninger (Küsnacht), P. Duroux (Sion), F. Kapp 

(Basel), L. Kayasseh (Basel), M. Meyer (Luzern), G. Münst (Uster), 

K. Schulthess (Zürich), P. Stadler (Payerne), C. Valli (Visp), M. Voirol 

(Yverdon-les-Bains), P.-Y. Zaugg (Frauenfeld). 

The Netherlands: A.J. Bosman-Laven (Hendrik Ido Ambacht), 

H.S. Emanuels (Zwijndrecht), F.I. Gulzar (Zwijndrecht), P.W.E. 

Haeck (Stadskanaal), W.W. Meijer (Den Helder), W.J. Rijsdijk 

(Hendrik Ido Ambacht), P.A.H. Top (Zwijndrecht), R.J. van Houten 

(Hendrik Ido Ambacht). 



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