Article Text

10 day sequential therapy was more effective than 10 day triple drug therapy for eradicating Helicobacter pylori infection
  1. Vincent Wai-Sun Wong, MD1,
  2. Francis Ka-Leung Chan, MD2
  1. 1Institute of Digestive Disease, Hong Kong, China
  2. 2The Chinese University of Hong Kong, Hong Kong, China

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 Q In patients with dyspepsia or peptic ulcer disease, is 10 day sequential therapy more effective than 10 day triple drug therapy for eradicating Helicobacter pylori infection?

    Clinical impact ratings GP/FP/Primary care ★★★★★★☆ Gastroenterology ★★★★★★☆ IM/Ambulatory care ★★★★★★☆


    Embedded ImageDesign:

    randomised controlled trial.

    Embedded ImageAllocation:


    Embedded ImageBlinding:

    blinded (patients, investigators, {data collectors, outcome assessors, data analysts, and data safety and monitoring committee}*).

    Embedded ImageFollow-up period:

    8 weeks.

    Embedded ImageSetting:

    2 hospitals in Bologna and Rome, Italy.

    Embedded ImagePatients:

    300 patients ⩾18 years of age (mean age 49 y, 64% women) with dyspepsia or peptic ulcers who had never received treatment for H Pylori infection. Exclusion criteria included use of proton pump inhibitors, H2 receptor antagonists, bismuth preparations, or antibiotics in the past 2 weeks; concomitant use of anticoagulants or ketoconazole and glucocorticoids; Zollinger Ellison syndrome; and surgery of the oesophagus or upper gastrointestinal tract.

    Embedded ImageIntervention:

    sequential (n = 150) or standard triple drug therapy (n = 150). Sequential therapy consisted of pantoprazole, 40 mg, amoxicillin, 1 g, and placebo twice daily for 5 days; and pantoprazole, 40 mg, clarithromycin, 500 mg, and tinidazole, 500 mg, twice daily for the next 5 days. Standard therapy consisted of pantoprazole, 40 mg, clarithromycin, 500 mg, and amoxicillin, 1 g, twice daily for 10 days.

    Embedded ImageOutcomes:

    eradication of H pylori infection (negative results on 13C urea breath tests at 4 and 8 wk). Secondary outcomes were eradication of clarithromycin or metronidazole resistant H Pylori infection, treatment adherence (>90% of medication taken), and adverse events.

    Embedded ImagePatient follow-up:

    96% (100% in intention-to-treat analysis).


    The table shows the results. Groups did not differ for treatment adherence, or incidence of major or minor adverse events. Adverse events included epigastric pain and mild diarrhoea.

    Sequential (Sequ) v standard triple drug therapy (Std) for HP infection in dyspepsia or peptic ulcers*


    10 day sequential therapy was more effective than 10 day triple drug therapy for eradicating Helicobacter pylori infection in patients with dyspepsia or peptic ulcer disease.

    Abstract and commentary also appear in ACP Journal Club.


    H pylori infection is an important cause of peptic ulcers and gastric cancer. Triple therapy comprising a proton pump inhibitor (PPI) and 2 antibiotics has been the standard treatment for H pylori, with an eradication rate of about 90%. However, widespread use of antibiotics has led to a dramatic increase in drug resistant strains. A recent meta-analysis reported an eradication rate of about 80% with standard triple therapy.1

    Can we do better? For patients in whom triple therapy has failed once, quadruple therapy (bismuth, PPI, metronidazole, and tetracycline) or levofloxacin-based triple therapy can help a significant proportion. Nevertheless, retreatment is inconvenient to patients, expensive, and involves repeated H pylori tests. The study by Vaira et al used an intention-to-treat analysis and found that 89% of patients who received sequential therapy had successful eradication compared with 77% of patients who received standard triple therapy. The benefits of sequential therapy stemmed mainly from the higher eradication rate of clarithromycin resistant H pylori. Side effect profiles of the 2 groups were similar.

    Like many important studies, the trial by Vaira et al brings more questions than answers. The study was conducted in Italy, a country with relatively low rates of metronidazole resistance and multidrug resistance. The high eradication rate achieved by sequential therapy in the subgroup with clarithromycin resistance was based on a small number of patients (n = 9). Whether similar success can be achieved in other countries still needs to be confirmed. Treatment failure also occurred in patients infected with susceptible strains. It would be useful to assess whether eradication rates could be increased further if either clarithromycin or tinidazole were given in the first 5 days in addition to the 2 drugs used in the current regimen. Moreover, the role of sequential therapy as salvage therapy for previous treatment failure should be explored.


    View Abstract


    • * Information provided by author.

    • See glossary.

    • For correspondence: Dr D Vaira, S. Orsola Hospital, Bologna, Italy. E-mail vairadin{at}

    • Source of funding: No external funding.

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