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Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

Aim : To study whether prophylaxis with lansoprazole could prevent relapse of ulcers after eradication of Helicobacter pylori in patients with NSAID-related peptic ulcers.

Methods : Patients who presented with peptic ulcers and were found to be infected with H. pylori while receiving NSAIDs were recruited into the study. They received, twice daily, lansoprazole 30 mg, amoxicillin 1 g and clarithromycin 500 mg for 1 week, followed by lansoprazole 30 mg daily for 4 weeks. Patients with healed ulcers and H. pylori eradicated were given naproxen 750 mg daily, and randomly assigned to receive lansoprazole 30 mg daily or no treatment for 8 weeks. The primary endpoint was the cumulative recurrence of symptomatic and complicated ulcers.

Results : At the end of the 8-week treatment period, significantly fewer patients (1/22, 4.5%, 95% confidence interval [CI] 0–23) in the lansoprazole group compared with the group that received H. pylori eradication alone (9/21, 42.9%, 95% CI 22–66) developed recurrence of symptomatic and complicated ulcers (log rank test P = 0.0025).

Conclusions : Lansoprazole significantly reduced the cumulative relapse of symptomatic and complicated ulcers in patients requiring NSAIDs after eradication of H. pylori.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed groups of pharmacological agents. However, patients taking NSAIDs chronically have about a two to sixfold increase in the risk of developing upper gastrointestinal events compared with patients not taking NSAIDs.1 Older patients, those with a past history of ulcer or bleeding, and those taking concomitant corticosteroids or anticoagulants, are at higher risk.1, 2

Misoprostol has been used successfully in the prophylaxis against ulcer development in chronic NSAIDs users. However, its use was limited by frequent side effects, including diarrhoea and abdominal pain, which necessitated drug withdrawal in more than 20% of the patients.3 A recent epidemiological study4 and a clinical endoscopic study5 suggested that a proton pump inhibitor could prevent NSAIDs induced peptic ulcers and their complications.

Eradication of Helicobacter pylori in those patients not taking NSAIDs markedly reduced the relapse of ulcer and its complications.6, 7 It is generally recommended that H. pylori should be eradicated in all patients with peptic ulcers and ulcers complications. Whether a proton pump inhibitor is required after eradication of H. pylori in chronic NSAIDs users is unknown. Recent studies have examined the role of omeprazole in prophylaxis against ulcer relapse in chronic NSAIDs users.5, 8 However, in these studies, H. pylori was not eradicated and therefore, did not answer this question. We aimed to study whether lansoprazole could prevent relapse of ulcers after eradication of H. pylori in chronic NSAIDs users who had a past history of peptic ulcers. We postulated that gastric acid suppression is required, even after eradication of H. pylori, to prevent relapse of ulcers.

Study population

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

We screened patients who presented to our endoscopy unit with a recent history (less than 1 week) of symptomatic or complicated gastroduodenal ulcers while taking stable and regular doses (at least 5 days per week for a minimum of 3 months) of one non-aspirin NSAID for eligibility into the trial. We recruited patients into the study if gastric and/or duodenal ulcer was detected on endoscopy, if they had diseases that required long-term continuous NSAIDs, if they were aged 18–80 years and if H. pylori could be demonstrated by a rapid urease test and/or histology on gastric antral biopsy. They were excluded from the study if they had oesophageal ulcers, pyloric obstruction or erosive oesophagitis at endoscopy, a history of H. pylori treatment, were taking antibiotics, bismuth compounds, sucralfate or proton pump inhibitors that might interfere with the status of H. pylori infection in the previous 6 weeks, if they had had previous gastric resective surgery, allergy to the study drugs, major organ failure and concomitant use of anticoagulants and corticosteroids.

Endoscopy

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

The study took place at the Queen Mary Hospital, Hong Kong, China from January 1998. All patients gave informed written consent to the study, which was approved by our local ethics committee. Suitable patients received upper endoscopy with a forward viewing videoscope (Olympus, Tokyo or Pentax, Tokyo, Japan) to detect any gastric or duodenal ulcers. An ulcer was defined as a break in the mucosa of at least 5 mm in diameter with unequivocal depth. Erosions were defined as a mucosal break of any size with no depth. Ulcer size was measured with the opened tips of standard biopsy forceps, which had a span of 5 mm. During endoscopy, we took two biopsies from the antrum and one biopsy from the body, respectively. One antral specimen was subjected to a standard rapid urease test (CLO test, Delta West, Bentley, Australia). A negative CLO test was defined as the absence of colour change after 24 h. The other antral biopsy specimen and the body specimen were subjected to histological examination of H. pylori using haematoxylin and eosin stain and Warthin-Starry stain, if necessary. Helicobacter pylori infection was considered to be present if either test was positive. Absence of H. pylori infection required all tests to be negative.

Treatment and randomization

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

All patients who met the inclusion and exclusion criteria received a 1 week course of antihelicobacter therapy containing lansoprazole 30 mg, amoxicillin 1 g and clarithromycin 500 mg, given twice daily. This was followed by treatment with lansoprazole 30 mg, given daily for 4 weeks. Repeat endoscopy was performed at the end of treatment to check for healing of ulcers and eradication of H. pylori using the methods described above. Patients with unhealed ulcers would be given 30 mg of lansoprazole daily for another 4 weeks. Patients who failed H. pylori eradication, defined as a positive rapid urease test or histology, would receive another 1 week course of triple therapy containing ranitidine bismuth citrate 400 mg, amoxicillin 1 g and metronidazole 400 mg, given twice daily. Patients with unhealed ulcers and two unsuccessful eradication treatments of H. pylori were taken out of the study.

Patients with ulcers healed and H. pylori eradicated at 4 week and 8 week endoscopy were given naproxen 750 mg in three divided doses for 8 weeks and were randomly assigned to receive either 30 mg of lansoprazole or no treatment, all given daily for 8 weeks (Figure 1). The treatment regimen was determined previously by a list of computer generated random numbers. The investigators who adjudicated the potential gastrointestinal events remained blinded to the treatment assignments until the end of the study.

image

Figure 1. Trial design.

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Follow-up

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

Patients were provided with antacids (Gelusil) and acetaminophen (up to 2000 mg daily) and allowed to take them as required. They were not permitted to take H2 receptor antagonists, sucralfate, proton pump inhibitors, prostaglandin analogues, antacids other than Gelusil, corticosteroids or anticoagulants.

Patients were followed-up at 4 weeks and 8 weeks after randomization. Blood counts, serum biochemistries and symptoms of dyspepsia were checked at each visit. Dyspepsia was defined as epigastric discomfort or pain. Severity was graded as none, mild (tolerated easily), moderate (interfered with normal activities) or severe (incapacitating). Patients were also advised to contact the research nurse if they had persistent ulcer symptoms (epigastric pain, dyspepsia or recurrent vomiting) not relieved by antacids, or if they had evidence of gastrointestinal bleeding or ulcer complications (melena, haematemesis or sudden onset of severe epigastric pain which may signify perforation).

Scheduled endoscopy was performed 8 weeks after the assigned treatment, if the patients remained asymptomatic and did not develop complications, to detect relapse of gastroduodenal ulcer. Patients who developed moderate or severe dyspepsia lasting ≥ 2 days which was not relieved by antacids, recurrent epigastric pain after antacids, or upper gastrointestinal bleeding (including a drop of haemoglobin ≥ 2 g/dL with positive occult blood in stool) before 8 weeks received early endoscopy. A 13C-urea breath test performed 4 weeks after all the study medications were stopped determined the final H. pylori status.

All remaining medication was returned at the follow-up visit. Drug compliance was assessed by counting unused tablets; patients were considered noncompliant if < 70% of naproxen and lansoprazole were consumed.

Endpoints

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

The primary endpoint was recurrent symptomatic and complicated ulcers. The secondary endpoint was cumulative relapse of all ulcers (asymptomatic, symptomatic and complicated ulcers) at 8 weeks. Symptomatic ulcers were defined as gastroduodenal ulcers associated with the presence of moderate to severe dyspepsia not relieved by antacids. Complicated ulcers were defined as gastroduodenal ulcers that presented with clinical evidence of upper gastrointestinal complications (including bleeding, obstruction and perforation).

Sample size

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

There were no data available about the relapse rate of ulcers and complications in NSAIDs users at the time of our study. We estimated that 40% of patients would have ulcer relapse after eradication of H. pylori at 8 weeks, while the addition of lansoprazole would further reduce the relapse rate to 10%. It was estimated that each treatment group should consist of a minimum of 40 patients to show an absolute difference of 30%, with a type I error of 0.05 and type II error of 0.2 (two sided test).

As recurrent ulcer complication is serious, we planned one interim analysis when about 40 patients were recruited. We used the O'Brien group multiple testing procedure for interim monitoring such that we would stop the trial if the between group difference in the primary endpoint reached a significance level of 0.005 in the interim analysis.9 The interim analysis was performed when 43 patients were recruited and as we found a significant difference (P = 0.0025) in the occurrence of primary endpoint between the two groups, the randomization was stopped early. The results we report here are based on all 43 randomized patients.

Statistical analysis

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

Differences between the treatment groups at baseline were analysed using the Pearson's Chi-squared test or Fisher's exact test for categorical data and the Mann–Whitney U-test for continuous variables.

Statistical analysis of clinical events was conducted on the intention-to-treat population which consisted of all patients who were randomized. The relative risks and 95% CI associated with proportions were calculated. We used the Kaplan–Meier survival estimates to analyse the probability of patients developing recurrent ulcers during follow-up. The log rank test was performed to test the differences in time to recurrent ulcer recurrences between defined groups. The Statistical Package for the Social Sciences (SPSS/PC 10.0 for windows, SPSS Inc, Chicago, IL, USA) program was used for all statistical calculations. All statistical tests were two-sided and statistical significance was defined as P < 0.05.

Characteristics of patients

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

Among 102 patients screened during the study period, 45 were suitable for entry into the trial and were given a 1 week course of triple therapy, followed by treatment with lansoprazole. Reasons for exclusion are given in Figure 1. Two patients had persistent H. pylori infection after the first course of eradication therapy; they received the second antihelicobacter therapy and H. pylori was eradicated in both patients. Two patients had persistent ulcers after repeated anti-ulcer treatment and were excluded from the study. The remaining 43 patients were given naproxen 750 mg daily and randomly assigned to receive lansoprazole treatment (n = 22) or no treatment (n = 21).

Patients in the two groups had similar baseline demographic characteristics with respect to sex, age, smoking or alcohol use, diagnosis and presence of co-morbid illness (Table 1). Over 50% of patients were aged 65 years or above. Co-morbid illnesses were present in 36% of the lansoprazole group and 43% of the no treatment group. More than 60% of the patients presented with ulcer bleeding.

Table 1.  Baseline characteristics of patients
 Lansoprazole group (n = 22)No treatment group (n = 21)
  • Abbreviations are as follows: RA, rheumatoid arthritis; OA, osteoarthritis.

  • ± Values are means ± s.d.

  • Shock was defined as a systolic blood pressure of less than 100 mmHg with a pulse rate of 100 beats/min or more.

Mean age, years (range)67.1 (41–78)70.2 (43–78)
Age ≥ 65 (%)13 (59.1)12 (57.1)
Female gender (%)8 (36.4)11 (52.4)
Diagnosis (RA/OA/other)6/15/14/17/0
Smoking (%)3 (13.6)2 (9.5)
Alcohol (%)2 (9.1)2 (9.5)
Co-morbid illnesses (%)8 (36.3)9 (42.9)
Location of ulcer (gastric ulcer/duodenal ulcer)18/415/6
Ulcer size11.2 ± 4.010.3 ± 4.3
Bleeding on presentation (%)17 (77.3)13 (61.9)
Characteristics of ulcer bleeding
Admission haemoglobin, g/dL9.5 ± 1.59.3 ± 1.2
Transfusion required, units1.1 ± 1.31.4 ± 1.2
 Before endoscopy0.76 ± 1.031.0 ± 1.0
 After endoscopy0.29 ± 0.470.38 ± 0.51
Median ulcer size, mm (range)10.0 (5–20)10.0 (5–20)
Admission pulse ≥ 100 beats/min (%)4 (23.5)3 (23.1)
Admission systolic BP < 100 mmHg (%)4 (23.5)2 (15.4)
Shock at presentation * (%)4 (23.5)2 (15.4)
Serum urea > 10 mmol/L10 (58.8)10 (76.9)
Location of ulcer (gastric ulcer/duodenal ulcer)14/310/3
Endoscopic haemostasis (%)7 (41.2)3 (23.1)

Compliance and withdrawal

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

Two patients (one in each group) consumed < 70% of the study medications, but all completed the follow-up. No patient experienced nongastrointestinal adverse events that necessitated the withdrawal of the study medications.

H. pylori status at end of study

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

One patient in the no treatment group had ulcer perforation during the follow-up and H. pylori could not be checked by endoscopic means at the end of the study; she did not return for a 13C-urea breath test. Of the remaining 42 patients, no patients in the no treatment group (0/20, 0%, 95% CI 0–17) compared with one patient in the lansoprazole group (1/22, 4.6%, 95% CI 0–23) had a relapse of H. pylori infection (P = 1.00), as determined by a 13C-urea breath test.

Outcomes (Table 2)

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References
Table 2.  Outcome of patients
 Lansoprazole group (n = 22)No treatment group (n = 21)
Total ulcers (%)2 (9.1)9 (42.9)
Complicated ulcers04
Bleeding03
Perforation01
Symptomatic ulcers (pain)15
Asymptomatic ulcers10
Location of ulcer (gastric ulcer/duodenal ulcer)1/17/2

In the lansoprazole group, two patients received early endoscopy before 8 weeks because of persistent epigastric pain. A gastric ulcer was found in one patient.

In the no treatment group, 10 patients received early endoscopy, seven because of persistent epigastric pain and three because of gastrointestinal bleeding. Gastric ulcers were found in seven patients and a duodenal ulcer was found in one patient. Of the three patients who had recurrent bleeding, one presented in shock and required endoscopic haemostasis to stop the bleeding. One other patient in the no treatment group developed ulcer perforation and required emergency omental patch repair. The patient recovered uneventfully.

At the end of the 8 week treatment period, 33 patients (21 patients in the lansoprazole group and 12 patients in the no treatment group) returned for the repeat final endoscopy. An ulcer was detected in one patient in the lansoprazole group and in none of the patients in the no treatment group.

Cumulative relapse of gastroduodenal ulcers (Table 2)

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

The cumulative incidence of symptomatic and complicated gastroduodenal ulcers at week 8 was 4.5% (1/22, 95% CI, 0–23) in the lansoprazole group and 42.9% (9/21, 95% CI 22–66) in the no treatment group. The log rank test showed a significant difference between the two groups in the time to recurrent events (P = 0.0025).

The cumulative incidence of all gastroduodenal ulcers at week 8 was 9.1% (2/22, 95% CI, 1–29) in the lansoprazole group and 42.9% (9/21, 22–66) in the no treatment group. The log rank test showed a significant difference between the two groups in the time to recurrent events (P = 0.0079).

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

The present study demonstrated that in patients who used NSAIDs chronically, eradication of H. pylori could not prevent relapse of symptomatic ulcers and ulcer complications. On the other hand, in those patients with H. pylori eradicated, lansoprazole significantly reduced relapse of peptic ulcers.

NSAIDs and H. pylori are the two most important causes of peptic ulceration. Since eradication of H. pylori markedly alters the natural history of peptic ulcer diseases and their complications, eradication has now been recommended as the standard therapy in patients who have a history of ulcers and complications. On the other hand, the role of H. pylori in patients who are using NSAIDs is controversial. Aalykke and his colleagues10 found that NSAIDs users with H. pylori infection had an almost twofold increased risk of bleeding peptic ulcer compared with NSAIDs users without H. pylori. However, other studies did not confirm this, with some showing either a protective role or no interaction of H. pylori in NSAIDs users who developed peptic ulcers.11–13 Despite these controversies, the results of our study demonstrated that eradication of H. pylori was alone clinically inadequate to prevent relapse of peptic ulcers and indeed, quite a significant proportion of our patients (> 40%) had a relapse of symptomatic and complicated ulcers after NSAIDs were resumed. On the other hand, eradication of H. pylori significantly prevented the development of ulcers in patients newly started on NSAIDs.14 This marked difference may be related to whether NSAIDs was used chronically or recently. Results from our previous study in chronic NSAIDs without a history of peptic ulcers,15 and from a study by Hawkey et al.16 in patients with a history of uncomplicated peptic ulcers, also showed that eradication of H. pylori in chronic NSAIDs users did not prevent the development or relapse of ulcers.

Recent studies have shown that omeprazole can effectively prevent the development of ulcers both in patients who have a past history of ulcers5, 8 and in patients who did not have ulcers before.17, 18 These studies suggest that NSAIDs related ulcers are acid responsive and can be prevented by strong gastric acid suppression. However, H. pylori was not routinely eradicated in all patients and in most of these studies, patients with and without H. pylori infection were pooled together. Although some evidence suggests that H. pylori infection may reduce the efficacy of the proton pump inhibitor in preventing ulcer relapse,19 and eradication of H. pylori also did not reduce ulcer relapse in chronic NSAIDs users,15, 16 it is generally recommended that H. pylori should be tested in present NSAIDs users who have a history of peptic ulcers; the infection should be cured if present.20 Several reasons support the eradication of H. pylori in these patients, despite the findings that H. pylori eradication alone is inadequate in preventing ulcer relapse in chronic NSAIDs users. First, it is logical to remove all potential ulcerogenic and transmissible agents in patients with ulcers. More importantly, it is impossible to decide clinically in an H. pylori infected individual whether the complicated ulcer is an H. pylori ulcer or an NSAIDs ulcer. Patients with H. pylori related ulcers might suffer a relapse with antecedent complications from the persistent H. pylori infection if NSAIDs and proton pump inhibitor prophylaxis are no longer needed in the future. It is therefore pertinent and clinically important to ask whether ulcer prophylaxis with an agent like a proton pump inhibitor can reduce the occurrence of ulcer relapse in these patients after H. pylori has been rendered negative, for which the information is lacking in the literature. The present study directly answers this question and we have demonstrated that lansoprazole, with eradication of H. pylori, significantly reduced the relapse of peptic ulcers compared with H. pylori eradication alone.

There were several limitations in our study. First, we followed the patients only for a total of 8 weeks while most of them would need the NSAIDs continuously for a longer period of time. However, we thought 8 weeks would be optimum for this study since a number of epidemiological studies had shown that most complications related to the use of NSAIDs occur within the first few months of therapy.1 Secondly, the sample size in this study was relatively small and we had recruited only 43 patients. Originally we planned a much larger patient population but because a highly significant relapse in the no treatment group was found, it would have been unethical to continue the study, especially when a high proportion of patients developed recurrent ulcer complications. Thirdly, we recruited patients with symptomatic ulcers as well as patients with more serious ulcer complications. However, we thought these ulcers were still clinically important, and this was the patient group where prophylaxis against ulcers would be considered because these patients would have an increased risk of recurrence. Indeed, a majority of the patients in our study presented initially with gastrointestinal bleeding.

In conclusion, our study did not support the use of H. pylori eradication alone in the prevention of ulcer relapse in patients who had a recent history of gastroduodenal ulcers. After eradication of H. pylori, it is advisable that these patients should still receive prophylactic treatment with drugs that have potent gastric acid suppression such as lansoprazole. Lansoprazole was shown in this study to be effective and significantly better than H. pylori eradication alone in the prevention of ulcer relapse.

Acknowledgements

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References

We are grateful to Nurse Specialist M. Chong, A. Tang, Endoscopy Nurse Ms K. W. Wong, S. Y. Tang, M. Y. Lee and K. K. Chang, M. Chow, W. M. Chan, F. K. Kwok, Y. K. Lam, Y. M. Lam, S. M. Yeung, S. Y. Lo for assistance, Ms April Wong for data management and Mr Stanley Yeung for statistical calculations. This work was supported fully by a grant from the peptic ulcer research fund (311/041/0372) of the University of Hong Kong.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Materials and methods
  5. Study population
  6. Endoscopy
  7. Treatment and randomization
  8. Follow-up
  9. Endpoints
  10. Sample size
  11. Statistical analysis
  12. Results
  13. Characteristics of patients
  14. Compliance and withdrawal
  15. H. pylori status at end of study
  16. Outcomes ()
  17. Cumulative relapse of gastroduodenal ulcers ()
  18. Discussion
  19. Acknowledgements
  20. References
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    Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis. Ann Intern Med 1991; 115: 78796.
  • 2
    Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 76972.
  • 3
    Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995; 123: 2419.
  • 4
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