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Original Investigation |

One-Day Quadruple Therapy Compared With 7-Day Triple Therapy for Helicobacter pylori Infection FREE

Luis F. Lara, MD; Gerardo Cisneros, MD; Michael Gurney, MD; Michael Van Ness, MD; David Jarjoura, PhD; Betty Moauro, RN; Ann Polen, MEd; Gregory Rutecki, MD; Frederick Whittier, MD
[+] Author Affiliations

From the Wake Forest University School of Medicine, Winston-Salem, NC (Dr Lara), and the Northeastern Ohio Universities College of Medicine Affiliated Hospitals, Canton (Drs Cisneros, Jarjoura, Rutecki, and Whittier and Ms Polen). Drs Gurney and Van Ness and Ms Moauro are in private practice in Canton. The authors have no relevant financial interest in this article.


Arch Intern Med. 2003;163(17):2079-2084. doi:10.1001/archinte.163.17.2079.
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Published online

Background  Eradication of Helicobacter pylori infection has had an impact on the treatment and recurrence rates of peptic ulcer disease and malignancies such as mucosa-associated lymphoid tissue lymphoma. Treatment options are cumbersome, expensive, and associated with side effects.

Methods  Randomized, prospective, open-labeled equivalence trial with a parallel-group design to compare eradication rates of H pylori with a 1-day, 4-drug regimen with a 7-day, 3-drug regimen. A total of 160 patients with dyspepsia and a Glasgow Dyspepsia Severity Score of at least 3 had a urea breath test labeled with carbon 14. Patients who tested positive were randomized to 1 of the 2 study groups. The study was designed to test the therapeutic equivalence of 1-day and 7-day regimens based on the percentage of H pylori eradication in each group at 5 weeks.

Results  The 1-day treatment group (n = 80) had a slightly higher eradication percentage (95%) than the 7-day group (90%). The possible inferiority of the 1-day treatment relative to the 7-day treatment, a 15% difference in the number of patients whose infection was not eradicated at 5 weeks, was rejected (P<.001; 90% confidence interval, 2.7%-11%). Both groups demonstrated a mean decrease of 7.5 points in the Glasgow Dyspepsia Severity Score. The 2 groups showed no significant differences in side effects. Patients whose treatment failed (4 in the 1-day treatment group and 7 in the 7-day treatment group) were re-treated for 10 days. One patient from the 7-day treatment group still tested positive after the second treatment.

Conclusions  The 1-day treatment proved to be statistically similar to the 7-day treatment for the eradication of H pylori in patients with dyspepsia and a positive urea breath test. Further evaluation will be necessary to determine whether the 1-day regimen is adequate for patients with peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, or gastric adenocarcinoma.

SINCE MARSHALL1 and Warren2 first described Helicobacter pylori in 1983, the observation that linked infection with this organism to gastritis and peptic ulcer disease has been extended. Despite recent reports of a decline in the prevalence of H pylori among patients with active ulcers, the association remains consistent.18

The eradication of H pylori infection in patients with peptic ulcer disease has been proven to be a cost-effective method to reduce ulcer recurrence rates and complications.916Helicobacter pylori is a well-described risk factor for the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma, which have high rates of remission when treated in their early stages. It is also believed that treatment might prevent the progression of gastric metaplasia.1722 Treatment of H pylori infection is currently accepted for patients with dyspepsia, even though dyspepsia and gastroesophageal reflux symptoms may worsen after H pylori eradication.2327

Multiple therapies to eradicate H pylori are available, and combinations have higher eradication rates than single-antibiotic regimens. Earlier therapies lasted up to 21 days and included up to 4 different medications. These therapies produced undesirable side effects such as nausea, vomiting, and diarrhea, which negatively affected compliance and, therefore, eradication rates.26,28,29

Shorter, triple-drug regimens have been developed, consisting of a proton-pump inhibitor (PPI), clarithromycin, and another antibiotic—typically, amoxicillin or metronidazole—given twice a day (bid). Fourteen-day, bid triple-drug regimens yield eradication rates of more than 90%, but at a greater cost than shorter treatments and with adverse side effects.3034

Seven-day, bid triple-drug regimens were shown to be as effective as 14-day regimens. They are recommended as first-time therapy by the European and Canadian Helicobacter pylori Consensus Conference because they produce high eradication rates, less severe side effects, and therefore good compliance.28,32 To achieve successful eradication of H pylori, an ideal therapy should be as simple and cost-effective as possible, and have minimal side effects.7,28

There are several studies of shorter therapies—lasting less than 1 week—for the eradication of H pylori. Two nonrandomized, uncontrolled studies consisting of a single-day treatment for H pylori infection demonstrated eradication rates greater than 72%.3342 A randomized study comparing a 7-day triple therapy with a 1-day quadruple therapy was stopped when interim analysis showed very poor (20%) eradication rates for the 1-day group.39 One-day therapeutic protocols, to our knowledge, have not been published in the United States. This equivalence trial compares eradication rates of a 1-day, 4-drug treatment with a 7-day, 3-drug treatment.

STUDY DESIGN

This study is a randomized, prospective, open-label equivalence trial with a parallel-group design. Patients with dyspepsia and H pylori infection were included if they had a positive urea breath test labeled with carbon 14 (14C-UBT) and a Glasgow Dyspepsia Severity Score (GDSS) above 2. They were identified during scheduled visits to the ambulatory internal medicine clinics of the Northeastern Ohio Universities College of Medicine Affiliated Hospitals at Canton (the Aultman Hospital and the Mercy Medical Center).

PATIENT SELECTION

Patients with dyspepsia symptoms were assessed with the GDSS, a validated tool for evaluating the severity and frequency of symptoms. This simple and rapidly administered test includes 8 items, with a maximum score of 20. Resolution of dyspepsia is considered to be successful if the GDSS decreases to less than 3.43

Patients were selected for a 14C-UBT only if their GDSS scores were 3 or higher. This test is an inexpensive and reliable alternative to endoscopy plus biopsy and histological examination or to the CLO test.40 We used the microCOUNT Model 9605 Liquid Scintillation Counter (Tri-Med Specialties Inc, Draper, Utah) for urea breath testing. Patients received an oral capsule of urea in which 12C was replaced with radioactive 14C (the exposure is less than for a chest radiography). The urea split by H pylori urease produces carbon dioxide and ammonia; the isotopes diffuse into the bloodstream and are expelled by the lungs as carbon dioxide C 14, which is qualitatively measurable. Measurements were taken 20 minutes after ingestion of the urea capsule to prevent a false-positive result due to oral flora. The patients were not taking antibiotics, bismuth, or acid-suppressive medications to avoid a false-negative result.4449

Inclusion criteria were dyspepsia, a GDSS of 3 or higher, and a positive 14C-UBT. Exclusion criteria included previous treatment of H pylori infection, pregnancy, age less than 18 years, personal or family history of gastrointestinal malignancy, antibiotic therapy in the previous 6 weeks, previous gastric surgery, hepatic insufficiency (Child-Pugh class B or C), creatinine clearance of less than 20 mL/min, use of a PPI in the previous 2 weeks, allergy to any of the medications included in the protocol, and danger signs or symptoms such as dysphagia, weight loss, or bleeding that would indicate a need for endoscopy.

TREATMENT GROUPS

Eligible patients signed an informed consent form approved by the institutional review board of both hospitals and were randomized to 1 of 2 study groups. The treatment group received a 1-day regimen consisting of two 262-mg tablets of bismuth subsalicylate 4 times daily (qid); of one 500-mg tablet of metronidazole qid; of 2 g of amoxicillin suspension qid; and of two 30-mg tablets of lansoprazole once daily. The control group received a 7-day regimen that included one 500-mg tablet of clarithromycin bid; two 500-mg tablets of amoxicillin bid; and one 30-mg tablet of lansoprazole bid.

All patients were asked to avoid antibiotics and acid suppression medications until a second 14C-UBT was performed 5 weeks after termination of therapy. Eradication of infection with H pylori was defined as a negative 14C-UBT 5 weeks after treatment. Patients in either group who had a positive second 14C-UBT were treated for 10 days with 500 mg of clarithromycin bid, 1 g of amoxicillin bid, 30 mg of lansoprazole bid, and 524 mg of bismuth subsalicylate qid. The 14C-UBT was repeated 5 weeks later. Side effects were identified using a questionnaire administered to patients after they finished the prescribed therapy, and patient compliance was assessed by direct pill counts. The GDSS was administered after therapy as well.

STATISTICAL METHODS

The trial was designed to test the therapeutic equivalence of 1-day and 7-day treatments based on the proportion of patients in each group whose H pylori infection was eradicated at 5 weeks.50 An equivalence trial was appropriate because eradication with the 7-day treatment is reported to be approximately 90%, which might be difficult to improve on.50,51 The sample size of 80 patients per group provided 90% power to reject the inferiority of the 1-day treatment at α = .05. It was assumed in the sample size calculation that the 7-day treatment would eradicate H pylori in 90% of patients. A difference of 15% in the number of patients with eradication in the 1-day group at the 5-week follow-up visit was considered the threshold of inferiority. A 1-sided confidence interval (CI) for the difference between the groups is the standard for equivalence trials such as this one because it protects the nominal α level.52 Other analyses compared GDSS scores at 5 weeks, adjusted for baseline differences between groups, and compared reported side effects with CIs.

Subjects with a GDSS score of at least 3 and a positive 14C-UBT were recruited from August 1998 to December 2000. Of the 160 patients enrolled, 10 patients (3 from the 1-day and 7 from the 7-day group) did not return for the 5-week 14C-UBT. Table 1 provides a comparison of the 1-day and 7-day groups at baseline for GDSS, sex, and age. The 95% CIs indicate no significant baseline differences between the groups regarding GDSS, sex, and alcohol use (the 95% CIs include zero). Patients were slightly older in the 7-day group than in the 1-day group. Statistical adjustments were made for all differences between groups in patient characteristics.

Table Graphic Jump LocationTable 1. Patient Characteristics at Baseline
ERADICATION PERCENTAGE

The 1-day treatment had a higher eradication percentage (95%) than the 7-day treatment (90%). According to our primary hypothesis test, the inferiority (a difference in rates ≥15%) of the 1-day treatment relative to the 7-day treatment was rejected at P<.001. Table 2 includes percentages of patients in each group whose 14C-UBT was negative at the 5-week evaluation. Table 2 also provides the lower limit of the 90% CI on the difference between the 1-day and the 7-day groups. The − 2.7% value is at the border of remaining consistent with these data, which allows the conclusion that, for a population similar to the one included in this study, the deficit in percentage of eradication in a 1-day treatment group, compared with a 7-day treatment group, would not be more than 2.7%. It is even possible that the 1-day treatment is superior to the 7-day treatment. (The upper limit of the CI on the difference indicates that the 1-day treatment is not more than 11% superior to the 7-day treatment; however, this study was not designed to test the superiority of the 1-day treatment, and it should be noted that it was not significantly superior.) Table 1 shows that the 7-day group was older, but that fewer patients in that group had a history of smoking. After adjusting for age and differences between the groups in sex, alcohol use, race, and history of smoking using a logistic regression model, it was found that the baseline differences had minimal impact on the results. The adjusted difference was 4% and the unadjusted difference was 4.5% in favor of the 1-day treatment. Table 2 also provides the change from baseline in GDSS scores. Both groups demonstrated a mean decrease of 7.5 percentage points.

Table Graphic Jump LocationTable 2. Eradication Percentages and GDSS Scores by Group at 5-Week Follow-up
SECONDARY ANALYSIS

None of the patients in either group expressed intolerance to their assigned treatment. None were grossly noncompliant with their treatment (ie, no 1-day patient crossed to the 7-day group or vice versa). Although intention-to-treat analyses are commonly used in superiority trials, they are inappropriate in equivalence trials because they bias toward equivalence.50 This issue did not arise in our study because all participants remained on their assigned treatment. Side effects (Table 3) were surveyed at the 5-week 14C-UBT. They included diarrhea, stool discoloration, nausea, dizziness, metallic taste in the mouth, loss of appetite, abdominal pain, headache, yeast infections, and constipation. Slightly more patients from the 7-day group (37%) than from the 1-day group (30%) said they experienced at least 1 of these side effects, but the difference was not significant. The 95% CIs on the difference did not reveal any significant differences between the 2 groups. Because side effects could have been associated with greater noncompliance in the 7-day treatment group, a search was done for a negative association between fewer side effects and eradication, and none was found (odds ratio, 0.9; P = .9). Adjusting for side effects had no impact on the positive difference observed between 1-day and 7-day eradication percentages.

Table Graphic Jump LocationTable 3. Percentage of Patients Reporting Side Effects by Group
TREATMENT FAILURES

Treatment was unsuccessful for 4 patients in the 1-day treatment group and 7 patients in the 7-day treatment group. Of the 4 patients in the 1-day treatment group who were subsequently treated with the 10-day course, 1 did not return for the second 5-week 14C-UBT and the other 3 tested negative. Of the 7 patients in the 7-day treatment group, 1 had a positive result at the second follow-up 14C-UBT but refused endoscopic evaluation or further therapy.

To successfully eradicate H pylori infection, the use of combination regimens known to have an acceptably high cure rate is vital. Therapies to treat H pylori infection should produce eradication rates of at least 90%.26,30,33,53 Furthermore, when developing a treatment plan, compliance, adverse reactions, and cost are additional factors that need to be considered.

Current regimens use a combination of 2 antibiotics with 1 or 2 nonantibiotic adjunctive agents. Fourteen-day, bid triple therapy regimens almost uniformly produce eradication rates higher than 90%, but these regimens are expensive and adverse effects such as nausea and diarrhea are common.33,5365 Lind et al55 demonstrated in the MACH (Metronidazole Amoxicillin Clarithromycin Helicobacter pylori) I study that a 7-day bid triple-therapy regimen achieves similar and acceptable results. This led to the Maastricht Consensus Report and the Canadian Helicobacter pylori Consensus Conference recommending a triple therapy consisting of a PPI, amoxicillin, plus 1 of 2 other antibiotics (clarithromycin or metronidazole) as first-line therapy to treat H pylori infection.28,32 This regimen achieves an eradication rate higher than 80% with intention-to-treat analysis and higher than 90% per protocol, at a lower cost.30,53,5565

Quadruple therapies lasting 7 to 14 days that include a bismuth compound produce excellent eradication rates, but these regimens are relegated to second-line therapy because their complex dosing schedule and less tolerable side-effect profiles decrease compliance.26,6668

Shorter therapies achieving eradication rates similar to those of 7- or 14-day treatments would be desirable to ensure patient compliance. Short therapies could only be recommended if they produced an acceptable eradication rate, and if patients subsequently tested negative for H pylori.33 The short therapies that have produced acceptable cure rates (up to 96%) have combined a bismuth salt, a PPI, and 2 antibiotics. Some of the regimens included a PPI for a longer time (up to 14 days) than the antibiotics.33,3538,54,56,6977 Eradication is confirmed on long-term follow-up when short therapies are used.54

Three European studies have addressed eradication using a single-day quadruple drug regimen. Tucci et al41 first achieved an eradication rate of 72%, and Takats et al42 then reported eradication in 76.5% of patients with duodenal ulcer and 83% of patients with dyspepsia. The randomized study by Wermeille et al,39 published after the initiation of our study, showed very poor eradication rates for their 1-day therapy group.

Amoxicillin is an antibiotic to which H pylori is sensitive in vitro, but has little impact when used in vivo as monotherapy at usual doses. However, when this antibiotic is used in high doses, only a short gastric contact time is needed to kill H pylori. Metronidazole is actively secreted into gastric juice and saliva, and its activity is independent of pH. Resistance to metronidazole can be avoided when it is given in combination with bismuth salicylate, a topical antimicrobial agent that directly disrupts the bacterial cell wall. Finally, PPIs increase intragastric pH, may enhance the effectiveness of the local immune response, reduce the mucosal washout of antibiotics, and may have bactericidal activity.3,12,21,30,31,55,63,65,72,76

The 14C-UBT is accepted as the noninvasive gold standard to diagnose H pylori infection, with reported sensitivity of more than 90% and specificity of more than 95%.26,30,4749 Shorter therapies have been criticized because of the possibility of suppression without eradication of H pylori, leading to false-negative 14C-UBT or histological findings, and there are concerns that sensitivity could drop to 90% in the follow-up 14C-UBT. Even though it has been demonstrated that 14 days off PPI will eliminate the false-negative rate, we elected to wait 5 weeks to repeat the 14C-UBT.4,66,77,78 Noninvasive tests for H pylori, including serum antibody tests and carbon 14–labeled breath tests, are reportedly as accurate in diagnosing the presence of H pylori as invasive tests.28,40,79,80 The 14C-UBT is an ideal test as it is accurate, cost-effective, and 3 to 4 times less expensive than invasive testing.40,44,79,81

An important consideration is the significantly lower cost of the 1-day regimen ($32), vs the 7-day regimen of the control group ($182). Eradication was achieved in 9 (82%) of 11 patients for whom initial therapy was not successful (subsequent therapy was not successful in 1 patient, and 1 patient did not have the follow-up 14C-UBT). Quadruple therapy, typically including bismuth, is very efficacious to treat patients for whom triple therapy has failed. Acceptable eradication rates have been achieved in as few as 7 days of quadruple therapy.8084

The GDSS was used to evaluate the severity of symptoms before and after therapy. There was a substantial decline in severity in both groups relative to baseline, but the mean scores were still above normal. This is consistent with other studies demonstrating the modest benefit of H pylori eradication in dyspepsia.26,27

The results observed in the present study demonstrate that eradication of H pylori infection can be achieved with a short-treatment regimen at a mean ± SD success rate of 95% ± 2.5%, a rate similar to those of longer combination therapies. The approach to H pylori eradication reported in this study is cost-effective, promotes patient compliance, and could simplify the role of primary care physicians in the treatment of H pylori infection. We advocate posttreatment testing in patients in whom eradication confirmation is desirable, eg, patients with persistent symptoms or a history of peptic ulcer disease.

Corresponding author and reprints: Frederick Whittier, MD, Affiliated Hospitals at Canton, 1320 Mercy Dr NW, Canton, OH 44708 (e-mail: nancy.castro@csauh.com).

Accepted for publication November 21, 2002.

This study was funded in part by a grant from the Aultman Health Foundation, Canton, Ohio. Some medications were provided by TAP Pharmaceutical Products Inc, Lake Forest, Ill. Other financial support was provided by the Canton Medical Education Foundation.

This study was presented in abstract form at the annual session of the American College of Physicians National Meeting; March 29, 2001; Atlanta, Ga.

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de Boer  WAvan Etten  RJSchade  RW  et al.  One-day intensified lansoprazole-quadruple therapy for cure of Helicobacter pylori infection. Aliment Pharmacol Ther. 1997;11109- 112
Link to Article
Lind  TVeldhuyzen van Zanten  SUnge  P  et al.  Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I study. Helicobacter. 1996;1138- 144
PubMed Link to Article
Lind  TMegraud  FUnge  P  et al.  The MACH2 study: role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies. Gastroenterology. 1999;116248- 253
PubMed Link to Article
Bazzoli  FZagari  RMFossi  S  et al.  Short-term low-dose triple therapy for the eradication of Helicobacter pyloriEur J Gastroenterol Hepatol. 1994;6773- 777
Link to Article
Labenz  JStolte  MRuhl  GHBecker  T  et al.  One-week low-dose triple therapy for the eradication of Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 1995;79- 11
PubMed
Bell  GDPowell  KUBurridge  SM  et al.  Rapid eradication of Helicobacter pylori infection. Aliment Pharmacol Ther. 1995;941- 46
PubMed Link to Article
de Boer  WAvan Etten  RJCoremans  ASchneeberger  PM Two-day ‘weekend' lansoprazole-quadruple therapy for Helicobacter pylori infection. Aliment Pharmacol Ther. 1998;1277- 81
PubMed Link to Article
Byrne  MFMurray  FE Current views on Helicobacter pylori eradication therapy. Ir Med J. 1998;918- 10
PubMed
Laine  LEstrada  RTrujillo  M  et al.  Once-daily therapy for H pylori infection: a randomized comparison of four regimens. Am J Gastroenterol. 1999;94962- 966
PubMed Link to Article
Laine  LSuchower  LFrantz  JConnors  ANeil  G Twice-daily, 10-day triple therapy with omeprazole, amoxicillin and clarithromycin for Helicobacter pylori eradication in duodenal ulcer disease: results of three multicenter, double-blind, United States trials. Am J Gastroenterol. 1998;932106- 2112
PubMed Link to Article
Bhasin  DKSharma  BCRay  PPathak  CMSingh  K Comparison of seven and fourteen days of lansoprazole, clarithromycin, and amoxicillin therapy for eradication of Helicobacter pylori: a report from India. Helicobacter. 2000;584- 87
PubMed Link to Article
Calvet  XGarcia  NLopez  TGisbert  JPGene  ERoque  M A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther. 2000;14603- 609
PubMed Link to Article
de Boer  WA Quadruple therapy: first- or second-line anti-Helicobacter pylori therapy? Res Clin Forums. 1998;2043- 47
Seppala  KKosunen  TUNuutinen  H  et al.  Cure of Helicobacter pylori infection after failed primary treatment: one-center results from 120 patients. Scand J Gastroenterol. 2000;35929- 934
PubMed
Baena-Diaz  JMLopez-Mompo  CRams-Rams  FGarcia-Lareo  MHernandez-Ibanez  RMTeruel-Gila  J Efficacy of a multistep strategy for Helicobacter pylori eradication: quadruple therapy with omeprazole, metronidazole, tetracycline and bismuth after failure of a combination of omeprazole, clarithromycin and amoxicillin. Med Clin (Barc). 2000;115617- 619
PubMed Link to Article
Tucci  APoli  LPaparo  GF  et al.  Weekend therapy for Helicobacter pylori infection. Am J Gastroenterol. 1998;93737- 742
PubMed Link to Article
Kimura,  KIdo  KSaifuku  et al.  A 1 hour topical therapy for the treatment of Helicobacter pylori infection. Am J Gastroenterol. 1995;9060- 63
PubMed
Nagahara  AMiwa  HYamada  TKurosawa  AOhkura  RSato  N Five-day proton pump inhibitor-based quadruple therapy regimen is more effective than 7-day triple therapy regimen for Helicobacter pylori infection. Aliment Pharmacol Ther. 2001;15417- 421
PubMed Link to Article
Catalano  FCatanzaro  RBranciforte  G  et al.  Five-day triple therapy in Helicobacter pylori-positive duodenal ulcer: an eighteen-month follow-up. J Clin Gastroenterol. 2000;31130- 136
PubMed Link to Article
Isumoto  HFurusu  HMorikawa  T  et al.  5-day vs 7-day triple therapy with rabeprazole, clarithromycin and amoxicillin for Helicobacter pylori eradication. Aliment Pharmacol Ther. 2000;141619- 623
PubMed Link to Article
Calabrese  CDiFebo  GAreni  AScialpi  CBiasco  GMiglioli  M Pantoprazole, azithromycin and tinidazole: short duration triple therapy for eradication of Helicobacter pylori infection. Aliment Pharmacol Ther. 2000;141613- 1617
PubMed Link to Article
Hurenkamp  GJVanDerEnde  AGrundmeijer  HGTytgat  GNVanDerHulst  RW Equally high efficacy of 4, 7 and 10-day triple therapies to eradicate Helicobacter pylori infection in patients with ulcer disease. Aliment Pharmacol Ther. 2000;141065- 1070
PubMed Link to Article
Nagahara  AMiwa  HOgawa  K  et al.  Addition of metronidazole to rabeprazole-amoxicillin-clarithromycin regimen for Helicobacter pylori infection provides an excellent cure rate with five-day therapy. Helicobacter. 2000;588- 93
PubMed Link to Article
van de Wouw  BAde Boer  WAHermsen  HWValkenburg  JGGeuskens  LMTytgat  GN Usefulness of the 14C urea breath test as a semi-quantitative monitoring instrument after therapy for Helicobacter pylori infection. Scand J Gastroenterol. 1997;32112- 117
PubMed Link to Article
Laine  LEstrada  RTrujillo  MKnigge  KFennerty  MB Effect of a proton-pump inhibitor therapy on diagnostic testing for Helicobacter pyloriAnn Intern Med. 1998;129547- 550
PubMed Link to Article
Cutler  AF Diagnostic tests for Helicobacter pylori infection. Gastroenterologist. 1997;5202- 212
PubMed
Gomoll  FFerrero  MCabezudo  JGuirao  RMontoro  M Quadruple therapy is effective for eradicating Helicobacter pylori after failure of triple proton-pump inhibitor-based therapy: a detailed, prospective analysis of 21 consecutive cases. Helicobacter. 1999;4222- 2225
PubMed Link to Article
Cutler  AFHavstad  SMa  CKBlaser  MJPerez-Perez  GISchubert  TT Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection. Gastroenterology. 1995;109136- 141
PubMed Link to Article
Danese  SArmuzzi  ARomano  A  et al.  Efficacy and tolerability of antibiotics in patients undergoing H pylori eradication. Hepatogastroenterology. 2001;48465- 467
PubMed
Dore  MPGraham  DYMele  R  et al.  Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter pylori infection. Am J Gastroenterol. 2002;97857- 860
PubMed Link to Article
Chiun-Ku  LPing-I  HKwok-Hung  L  et al.  One-week quadruple therapy is an effective salvage regimen for Helicobacter pylori infection in patients after failure of standard triple therapy. J Clin Gastroenterol. 2002;34547- 551
PubMed Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. Patient Characteristics at Baseline
Table Graphic Jump LocationTable 2. Eradication Percentages and GDSS Scores by Group at 5-Week Follow-up
Table Graphic Jump LocationTable 3. Percentage of Patients Reporting Side Effects by Group

References

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de Boer  WAvan Etten  RJSchade  RW  et al.  One-day intensified lansoprazole-quadruple therapy for cure of Helicobacter pylori infection. Aliment Pharmacol Ther. 1997;11109- 112
Link to Article
Lind  TVeldhuyzen van Zanten  SUnge  P  et al.  Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I study. Helicobacter. 1996;1138- 144
PubMed Link to Article
Lind  TMegraud  FUnge  P  et al.  The MACH2 study: role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies. Gastroenterology. 1999;116248- 253
PubMed Link to Article
Bazzoli  FZagari  RMFossi  S  et al.  Short-term low-dose triple therapy for the eradication of Helicobacter pyloriEur J Gastroenterol Hepatol. 1994;6773- 777
Link to Article
Labenz  JStolte  MRuhl  GHBecker  T  et al.  One-week low-dose triple therapy for the eradication of Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 1995;79- 11
PubMed
Bell  GDPowell  KUBurridge  SM  et al.  Rapid eradication of Helicobacter pylori infection. Aliment Pharmacol Ther. 1995;941- 46
PubMed Link to Article
de Boer  WAvan Etten  RJCoremans  ASchneeberger  PM Two-day ‘weekend' lansoprazole-quadruple therapy for Helicobacter pylori infection. Aliment Pharmacol Ther. 1998;1277- 81
PubMed Link to Article
Byrne  MFMurray  FE Current views on Helicobacter pylori eradication therapy. Ir Med J. 1998;918- 10
PubMed
Laine  LEstrada  RTrujillo  M  et al.  Once-daily therapy for H pylori infection: a randomized comparison of four regimens. Am J Gastroenterol. 1999;94962- 966
PubMed Link to Article
Laine  LSuchower  LFrantz  JConnors  ANeil  G Twice-daily, 10-day triple therapy with omeprazole, amoxicillin and clarithromycin for Helicobacter pylori eradication in duodenal ulcer disease: results of three multicenter, double-blind, United States trials. Am J Gastroenterol. 1998;932106- 2112
PubMed Link to Article
Bhasin  DKSharma  BCRay  PPathak  CMSingh  K Comparison of seven and fourteen days of lansoprazole, clarithromycin, and amoxicillin therapy for eradication of Helicobacter pylori: a report from India. Helicobacter. 2000;584- 87
PubMed Link to Article
Calvet  XGarcia  NLopez  TGisbert  JPGene  ERoque  M A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther. 2000;14603- 609
PubMed Link to Article
de Boer  WA Quadruple therapy: first- or second-line anti-Helicobacter pylori therapy? Res Clin Forums. 1998;2043- 47
Seppala  KKosunen  TUNuutinen  H  et al.  Cure of Helicobacter pylori infection after failed primary treatment: one-center results from 120 patients. Scand J Gastroenterol. 2000;35929- 934
PubMed
Baena-Diaz  JMLopez-Mompo  CRams-Rams  FGarcia-Lareo  MHernandez-Ibanez  RMTeruel-Gila  J Efficacy of a multistep strategy for Helicobacter pylori eradication: quadruple therapy with omeprazole, metronidazole, tetracycline and bismuth after failure of a combination of omeprazole, clarithromycin and amoxicillin. Med Clin (Barc). 2000;115617- 619
PubMed Link to Article
Tucci  APoli  LPaparo  GF  et al.  Weekend therapy for Helicobacter pylori infection. Am J Gastroenterol. 1998;93737- 742
PubMed Link to Article
Kimura,  KIdo  KSaifuku  et al.  A 1 hour topical therapy for the treatment of Helicobacter pylori infection. Am J Gastroenterol. 1995;9060- 63
PubMed
Nagahara  AMiwa  HYamada  TKurosawa  AOhkura  RSato  N Five-day proton pump inhibitor-based quadruple therapy regimen is more effective than 7-day triple therapy regimen for Helicobacter pylori infection. Aliment Pharmacol Ther. 2001;15417- 421
PubMed Link to Article
Catalano  FCatanzaro  RBranciforte  G  et al.  Five-day triple therapy in Helicobacter pylori-positive duodenal ulcer: an eighteen-month follow-up. J Clin Gastroenterol. 2000;31130- 136
PubMed Link to Article
Isumoto  HFurusu  HMorikawa  T  et al.  5-day vs 7-day triple therapy with rabeprazole, clarithromycin and amoxicillin for Helicobacter pylori eradication. Aliment Pharmacol Ther. 2000;141619- 623
PubMed Link to Article
Calabrese  CDiFebo  GAreni  AScialpi  CBiasco  GMiglioli  M Pantoprazole, azithromycin and tinidazole: short duration triple therapy for eradication of Helicobacter pylori infection. Aliment Pharmacol Ther. 2000;141613- 1617
PubMed Link to Article
Hurenkamp  GJVanDerEnde  AGrundmeijer  HGTytgat  GNVanDerHulst  RW Equally high efficacy of 4, 7 and 10-day triple therapies to eradicate Helicobacter pylori infection in patients with ulcer disease. Aliment Pharmacol Ther. 2000;141065- 1070
PubMed Link to Article
Nagahara  AMiwa  HOgawa  K  et al.  Addition of metronidazole to rabeprazole-amoxicillin-clarithromycin regimen for Helicobacter pylori infection provides an excellent cure rate with five-day therapy. Helicobacter. 2000;588- 93
PubMed Link to Article
van de Wouw  BAde Boer  WAHermsen  HWValkenburg  JGGeuskens  LMTytgat  GN Usefulness of the 14C urea breath test as a semi-quantitative monitoring instrument after therapy for Helicobacter pylori infection. Scand J Gastroenterol. 1997;32112- 117
PubMed Link to Article
Laine  LEstrada  RTrujillo  MKnigge  KFennerty  MB Effect of a proton-pump inhibitor therapy on diagnostic testing for Helicobacter pyloriAnn Intern Med. 1998;129547- 550
PubMed Link to Article
Cutler  AF Diagnostic tests for Helicobacter pylori infection. Gastroenterologist. 1997;5202- 212
PubMed
Gomoll  FFerrero  MCabezudo  JGuirao  RMontoro  M Quadruple therapy is effective for eradicating Helicobacter pylori after failure of triple proton-pump inhibitor-based therapy: a detailed, prospective analysis of 21 consecutive cases. Helicobacter. 1999;4222- 2225
PubMed Link to Article
Cutler  AFHavstad  SMa  CKBlaser  MJPerez-Perez  GISchubert  TT Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection. Gastroenterology. 1995;109136- 141
PubMed Link to Article
Danese  SArmuzzi  ARomano  A  et al.  Efficacy and tolerability of antibiotics in patients undergoing H pylori eradication. Hepatogastroenterology. 2001;48465- 467
PubMed
Dore  MPGraham  DYMele  R  et al.  Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter pylori infection. Am J Gastroenterol. 2002;97857- 860
PubMed Link to Article
Chiun-Ku  LPing-I  HKwok-Hung  L  et al.  One-week quadruple therapy is an effective salvage regimen for Helicobacter pylori infection in patients after failure of standard triple therapy. J Clin Gastroenterol. 2002;34547- 551
PubMed Link to Article

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