Omeprazole plus triple therapy increased Helicobacter pylori eradication
ACP J Club. 1995 Sept-Oct;123:37. doi:10.7326/ACPJC-1995-123-2-037
de Boer W, Driessen W, Jansz A, Tytgat G. Effect of acid suppression on efficacy of treatment for Helicobacter pylori infection. Lancet. 1995 Apr 1; 345:817-20.
To determine whether omeprazole added to triple therapy (bismuth, tetracycline, and metronidazole) improves eradication of Helicobacter pylori and reduces side effects in patients with peptic ulcer disease.
Randomized controlled trial with 4 to 6 weeks of follow-up.
An outpatient clinic of a community hospital in the Netherlands.
108 consecutive patients (mean age 51 y, 67% men) with peptic ulcer disease and biopsy-proven H. pylori infection. Exclusion criterion was pregnancy. Most patients were taking H2-blockers at diagnosis. Active ulcers were treated for 4 to 6 weeks with H2-blockers before inclusion in the study. Follow-up was 100%, and 97% of patients finished treatment.
All patients received triple therapy for 7 days (colloid bismuth subcitrate, 120 mg 4 times/d before meals and at night; tetracycline hydrochloride, 500 mg 4 times/d at meals and at night; and metronidazole, 500 mg 3 times/d at meals). 54 patients were also assigned to omeprazole, 20 mg 2 times/d (before breakfast and dinner) for 10 days, beginning 3 days before triple therapy. H2-blockers were not allowed, and alcohol use was discouraged. Patients were told to expect slight nausea; metallic taste; and frequent, loose, black stool.
Main outcome measures
Cure based on laboratory- and culture-proven eradication of H. pylori and self-reported adverse effects. Endoscopy was done 4 to 6 weeks after therapy.
Patients receiving omeprazole plus triple therapy, compared with patients receiving only triple therapy, had a higher cure rate (P = 0.02) (Table). 2% of patients receiving omeprazole reported mild vomiting, whereas 8% of patients receiving triple therapy reported mild vomiting and 9% reported severe vomiting (P = 0.02). The groups did not differ for other adverse effects (anorexia, nausea, metallic taste, dizziness, stomach pain, and diarrhea).
The addition of omeprazole to 7 days of triple therapy (bismuth, tetracycline, and metronidazole) increased eradication of Helicobacter pylori and decreased vomiting in patients with peptic ulcer disease.
Source of funding: No external funding.
For article reprint: Dr. W. de Boer, Department of Internal Medicine, Sint Anna Ziekenhuis, Postbus 10, 5340 BE Oss, the Netherlands, FAX 31-4126-21222.
Table. Omeprazole plus triple therapy vs triple therapy alone for eradication of Helicobacter pylori at 4 to 6 weeks*
|Outcomes||Omeprazole + triple therapy||Triple therapy alone||RBI (95% CI)||NNT (CI)|
|Cure rate||98.1%||83.3%||17.8% (5.3 to 38)||7 (4 to 22)|
*Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.
Multiple drug combinations have been tried in the search for the ideal regimen to eradicate H. pylori infection. Triple therapy with bismuth, tetracycline, and metronidazole for 14 days combined with H2-blockers or proton-pump inhibitors for symptom relief provides consistent cure rates of 90% to 95%. This regimen requires 15 pills a day (16 or 17 with H2-blockers or proton-pump inhibitors), which can threaten compliance. Side effects that threaten treatment discontinuation average 33%. Metronidazole resistance is variable and not easily tested.
This well-designed study by de Boer and colleagues is a welcome addition to clinical practice. The omeprazole plus triple therapy regimen is highly successful. The reduction in side effects and the number of therapy days will probably enhance patient compliance and acceptance. Neither age nor smoking history appeared to affect treatment success. Pretreatment with omeprazole does not diminish effectiveness, as is often seen when omeprazole is combined with amoxicillin. This is important for clinical practice because therapy is often started before the diagnosis of H. pylori is confirmed. 3 patients in the study and 6 additional patients with metronidazole-resistant strains were successfully treated with the omeprazole and triple therapy combination. If the addition of omeprazole can overcome metronidazole resistance, this successful, affordable, and tolerable regimen will be of even wider clinical usefulness.
Questions remain. Is this quadruple therapy sufficient for healing without a full course of traditional antiulcer therapy? A recent similar study suggests that it might be (1). However, the pretreatment of many patients with H2-blockers in this study prevents this conclusion. Direct comparison of this regimen to successful dual therapy with omeprazole plus amoxicillin or clarithromycin (2) or to triple therapy with omeprazole, clarithromycin, and metronidazole (3) is needed. We await simpler, safer treatment regimens to cure peptic ulcer.
Philip O. Katz, MD
The Johns Hopkins Bayview Medical CenterBaltimore, Maryland, USA
2. Bayerdörffer E, Miehlke S, Mannes GA, et al. Double-blind trial of omeprazole and amoxicillin to cure Helicobacter pylori infection in patients with duodenal ulcers. Gastroenterology. 1995;108:1412-7.
The commentary by Katz is partly outdated. Head to head studies with the mentioned dual and triple therapies have now all been done.
Our study is still relevant to clinical practice today. Quadruple therapy has now earned a position as standard second-line treatment after failure of a less complex regimen. Recently, a new monocapsule which contains bismuth, tetracycline, and metronidazole became available, which greatly simplifies the regimen. A monocapsule-based quadruple therapy is in the making and may be the therapy for the future, because clarithromycin resistance is rapidly increasing in many countries, including the United States.
Large studies comparing the best therapies have not yet been done, and H. pylori therapy is still not truly evidence based. Moreover, local prevalence of antibiotic resistance and remaining options for retreatment dictate the choice of therapy (1).
Wink A. de Boer
Sint Anna ZiekenhuisOss, The Netherlands