Clinical trial NCT02576236: Therapeutic Trial Comparing Triple Therapy Guided by the PCR Detection of Clarithromycin Resistance vs Empiric Concomitant Quadruple Therapy for Helicobacter Pylori Infection
Official title: Comparison of the Efficacy and Tolerance of Triple Therapy Guided by the PCR Detection of Clarithromycin Resistance WITH Empiric Concomitant Quadruple Therapy for Helicobacter Pylori Infection: a Randomised Multicentre Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: H Pylori Infection Eradication
Antibiotics Therapeutic Strategies
H Pylori Eradication
Keywords: Naïve patient
Suspicion of H pylori infection
Endoscopy
Antibiotics therapeutic strategies
Urea breath test
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-10-15
Enrollment: 2500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The H pylori infection remains a public health problem. The eradication rate with the first line triple therapy (PPI-amoxicillin-clarithromycin) is insufficient (estimated at 70%) due to the frequency of resistance to clarithromycin, which reaches 21% in France. Until now,European and French consensus recomended tofavor sequential therapy (5 days PPI-amoxicillin and 5 days PPI-clarithromycin-metronidazole) or quadruple bismuth therapy ( 10 days PPI-tetracyclin,-metronidazole- bismuth). Studies in countries with low prevalence of clarithromycin resistance reported eradication rate of 85% with sequential therapy and reported a low impact of clarithromycin resistance on the effectiveness of this treatment. However, recent studies suggest a greater impact of clarithromycin resistance. Recent meta-analysis shows that empiric sequential therapy is less efficacious than concomitant quadruple therapy. Therefore, recent Maastricht V / Florence meeting October 7-8 2015) recommended to abandon sequential therapy and to favor 14 days concomitant therapy in first line in order to reach an eradication rate \>90%.

In a multicenter randomized clinical trial (HELICOSTIC 2010-2011 AO ICST 2009), we compared a triple therapy guided by the results of a PCR test that detects resistance to clarithromycin and levofloxacin (HelicoDR ®) to empirical triple therapy (PPI-amoxicillin-clarithromycin). 1384 patients and among them 526 infected patients were enrolled in 10 centers. The results in 415 patients were 73.1% for the empirical treatment versus 85.5% (p \<0.001) for the treatment guided by PCR HelicoDR®. This study also demonstrated the limits of the test HelicoDR®: onerous, possibility of contamination, little practical contribution of the determination of resistance to quinolones.

Moreover, it has been shown that triple therapy efficiency could be optimized by increasing duration up to 14 days and increasing dose of PPI to 40mg b.d;.and eradications rates \> 90% were reported with susceptible to clarithromycin strains.

Adverse events are less common with optimized triple therapy than with concomitant quadruple therapy.

The main objective is to compare the efficacy of optimized triple therapy guided by the results of a PCR test (eradication rates 90% hypothesized) with quadruple concomitant therapy (eradication rate 90% hypothesized).

The secondary objective is to determine side effects of optimized guided triple therapy as well as the quadruple concomitant therapy in France.


Eligibility criteria: Inclusion Criteria:

* Adult patients ≥ 18 years
* Hospitalized or out-patients referred to one of the participating centers for upper gastrointestinal endoscopy
* Who did not received a previous eradication treatment
* Willing to participate and signed inform consent. Finally only patients with bacteriologically documented H. pylori infection (PCR) will be included.

Exclusion Criteria:

* Patient having already been treated to eradicate H pylori
* No affiliation to social insurance
* Person under legal protection
* Refusal for signing informed consent
* Patient included in another trial with medication
* Patient unable to take oral medication ongoing
* Patient with severe life-threatening disease in the short term
* Contraindication to the PPIs, amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracyclin or bismuth
* Patient under treatment with antibiotics or PPI without possibility of interruption for 4 weeks
* Pregnant or breast-feeding woman

Primary outcomes:
measure: Eradication rate on the basis of a negative C13 - urea breath test done 6-12 weeks after the end of treatment
timeFrame: at 34 month
Secondary outcomes:
measure: Safety criteria will include all adverse events occurring in the two treatment groups
timeFrame: at 34 month
Other outcomes:
Locations:
city: Creteil
country: France
facility: Henri Mondor Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean-Charles Delchier, MD
role: PRINCIPAL_INVESTIGATOR
References: