Optimum duration of regimens for Helicobacter pylori eradication

  • Review
  • Intervention




The optimal duration for Helicobacter pylori (H. pylori) eradication therapy is controversial, with recommendations ranging from 7 to 14 days. Several systematic reviews have attempted to address this issue but have given conflicting results and limited their analysis to proton pump inhibitor (PPI), two antibiotics (PPI triple) therapy. We performed a systematic review and meta-analysis to investigate the optimal duration of multiple H. pylori eradication regimens.


The primary objective was to assess the relative effectiveness of different durations (7, 10 or 14 days) of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events.

Search methods

The Cochrane Library, MEDLINE, EMBASE, and CINAHL were searched up to December 2011 to identify eligible randomised controlled trials (RCTs). We also searched the proceedings of six conferences from 1995 to 2011, dissertations and theses, and grey literature. There were no language restrictions applied to any search. 

Selection criteria

Only parallel group RCTs assessing the efficacy of one to two weeks duration of first line H. pylori eradication regimens in adults were eligible. Within each regimen, the same combinations of drugs at the same dose were compared over different durations. Studies with at least two arms comparing 7, 10, or 14 days were eligible. Enrolled participants needed to be diagnosed with at least one positive test for H. pylori on the basis of a rapid urease test (RUT), histology, culture, urea breath test (UBT), or a stool antigen test (HpSA) before treatment. Eligible trials needed to confirm eradication of H. pylori as their primary outcome at least 28 days after completion of eradication treatment. Trials using only serology or a polymerase chain reaction (PCR) to determine H. pylori infection or eradication were excluded.

Data collection and analysis

Study eligibility and data extraction were performed by two independent review authors. Data analyses were performed within each type of intervention, for both primary and secondary outcomes. The relative risk (RR) and number needed to treat (NNT)/number needed to harm (NNTH) according to duration of therapy were calculated using the outcomes of H. pylori persistence and adverse events. A random-effects model was used. Subgroup analyses and sensitivity analyses were planned a priori.

Main results

In total, 75 studies met the inclusion criteria. Eight types of regimens were reported with at least two comparative eligible durations. They included: PPI + two antibiotics triple therapy (n = 59), PPI bismuth-based quadruple therapy (n = 6), PPI + three antibiotics quadruple therapy (n = 1), PPI dual therapy (n = 2), histamine H2-receptor antagonist (H2RA) bismuth quadruple therapy (n = 3), H2RA bismuth-based triple therapy (n = 2), H2RA + two antibiotics triple therapy (n = 3), and bismuth + two antibiotics triple therapy (n = 2). Some studies provided data for more than one regimen or more than two durations.

For the PPI triple therapy, 59 studies with five regimens were reported: PPI + clarithromycin + amoxicillin (PCA); PPI + clarithromycin + a nitroimidazole (PCN); PPI + amoxicillin + nitroimidazole (PAN); PPI + amoxicillin + a quinolone (PAQ); and PPI + amoxicillin + a nitrofuran (PANi). Regardless of type and dose of antibiotics, increased duration of PPI triple therapy from 7 to 14 days significantly increased the H. pylori eradication rate (45 studies, 72.9% versus 81.9%), the RR for H. pylori persistence was 0.66 (95% CI 0.60 to 0.74), NNT was 11 (95% CI 9 to 14). Significant effects were seen in the subgroup of PCA (34 studies, RR 0.65, 95% CI 0.57 to 0.75; NNT 12, 95% CI 9 to 16); PAN (10 studies, RR 0.67, 95% CI 0.52 to 0.86; NNT = 11, 95% CI 8 to 25); and in PAQ (2 studies, RR 0.37, 95% CI 0.16 to 0.83; NNT 3, 95% CI 2 to 10); but not in PCN triple therapy (4 studies, RR 0.87, 95% CI 0.71 to 1.07). Significantly increased eradication rates were also seen for PPI triple therapy with 10 versus 7 days (24 studies, 79.9% versus 75.7%; RR 0.80, 95% CI 0.72 to 0.89; NNT 21, 95% CI 15 to 38) and 14 versus 10 days (12 studies, 84.4% versus 78.5%; RR 0.72, 95% CI 0.58 to 0.90; NNT 17, 95% CI 11 to 46); especially in the subgroup of PAC for 10 versus 7 days (17 studies, RR 0.80, 95% CI 0.70 to 0.91) and for 14 versus 10 days (10 studies, RR 0.69, 95% CI 0.52 to 0.91). A trend towards increased H. pylori eradication rates was seen with increased duration of PCN for 10 versus 7 days, and of PAN for 10 versus 7 days and 14 versus 10 days, though this was not statistical significant. The proportion of patients with adverse events, defined by authors, was marginally significantly increased only between 7 days and 14 days (15.5% versus 19.4%; RR 1.21, 95% CI 1.06 to 1.37; NNTH 31, 95% CI 18 to 104) but not for other duration comparisons. The proportion of patients discontinuing treatment due to adverse events was not significantly different between treatment durations.

Only limited data were reported for different durations of regimens other than PPI triple therapy. No significant difference of the eradication rate was seen for all regimens according to different durations except for H2RA bismuth quadruple therapy, where a significantly higher eradication rate was seen for 14 days versus 7 days, however only one study reported outcome data.

Authors' conclusions

Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy; more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.    

Plain language summary

Ideal length of treatment for Helicobacter pylori (H. pylori) eradication

The ideal duration of therapy for H. pylori eradication is controversial, with recommendations ranging from 7 to 14 days. A proton pump inhibitor (PPI) plus two antibiotics is the most commonly used first treatment to remove H. pylori infection. Current data suggest that increasing the length of treatment to 14 days of a PPI plus amoxicillin and clarithromycin or amoxicillin and a nitroimidazole significantly increases the eradication rate, while increasing the adverse events by a small amount. Based on the overall evidence, the ideal length of treatment with a PPI plus amoxicillin and clarithromycin is at least 14 days.

எளியமொழிச் சுருக்கம்

ஹெலிகோபாக்டெர் பைலோரி (ஹச். பைலோரி) அழிப்புக்கு சிறந்த சிகிச்சை காலம்

எச் பைலோரி அழித்தலுக்கு சிறந்த சிகிச்சை கால அளவு எது என்பது சர்ச்சைக்குரியதாக உள்ளது. சிகிச்சை கால அளவு 7 ல் இருந்து 14 நாட்கள் வரை பரிந்துரைக்க படுகிறது எச் பைலோரி தொற்றுக்கு பொதுவாக முதல் சிகிச்சையாக புரோட்டான் இறைப்பி மறிப்பி (proton pump inhibitor (PPI) உடன் 2 நுண்ணுயிர்க் கொல்லி சேர்த்து அளிக்கபடும் பிபிஐ + அமாக்சிசிலினும் க்ளாரித்ரோமைசின் அல்லது ஆமோக்சிசிலின் மற்றும் ஒரு நைட்ராமிடஸால் கொண்ட 14 நாட்களின் சிகிச்சை காலம் அதிகரிப்பது குறிப்பிடத்தக்க அளவு, அழிப்பு விகிதம் அதிகரிக்கிறது மற்றும் சிறிய அளவு தீங்கு விளைவிக்கும் நிகழ்வுகள் குறைக்கும் என்று தற்போதைய தரவு ஒரு கூறுகின்றன. ஒட்டுமொத்த சான்றுகளின் அடிப்படையில் பிபிஐ (PPI) பிளஸ் அமாக்சிசிலினும் (amoxicillin) க்ளாரித்ரோமைசின் (clarithromycin) கொண்டு சிகிச்சை குறைந்தது 14 நாட்கள் அளிப்பது சிறந்தாகும்.

மொழிபெயர்ப்பு குறிப்புகள்

மொழிபெயர்ப்பு: இர. ரவி மற்றும் சி.இ.பி.என்.அர் குழு.

Laienverständliche Zusammenfassung

Die optimale Behandlungsdauer für Heliobacter pylori (H. pylori) Eradikation

Die optimale Behandlungsdauer für H. pylori Eradikation is nicht eindeutig mit Empfehlungen von 7 bis 14 Tagen. Protonenpumpenhemmer (Protonenpumpen-Inhibitoren, PPI) plus zwei Antibiotika ist die gebräuchlichste Behandlung zur Eradikation von H. pylori Infektionen. Aktuelle Daten weisen darauf hin, dass eine verlängerte Behandlungsdauer von 14 Tagen mit einem PPI plus Amoxicilin und Clarithromycin oder Amoxicillin und Nitroimidazol die Eradikationsrate signifikant verbessert während die unerwünschten Ereignissen nur gering erhöht werden. Insgesamt zeigt die Evidenz, dass die optimale Behandlungsdauer mit einem PPI plus Amoxicillin und Clarithromycin mindestens 14 Tage beträgt.

Anmerkungen zur Übersetzung

I. Töws, Koordination durch Cochrane Schweiz