Therapeutic Trial Comparing Triple Therapy Guided by the PCR Detection of Clarithromycin Resistance vs Empiric Concomitant Quadruple Therapy for Helicobacter Pylori Infection (Hepysé)

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

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.

Study Overview

• Status: Unknown
• Conditions: H Pylori Eradication; H Pylori Infection Eradication; Antibiotics Therapeutic Strategies
• Intervention / Treatment: Other: Triple therapy guided by the result of the molecular resistance test; Other: Quadruple concomitant therapy treatment

• Study Type: Interventional
• Enrollment (Anticipated): 2500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94010
    • Recruiting
    • Henri Mondor Hospital
    • Contact: Dalila Selmane, CRA; Phone Number: +33 (0)1 49 81 33 86; Email: dalila.selmane@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Triple therapy guided by result of the molecular resistance; If clarithromycin S : high dose PPI (Esoméprazole 40mg X 2/ d) - amoxicillin 1gX2 / d - clarithromycin 500mgX2 / d The total duration of treatment is 14 days.; If clarithromycin R: high dose PPI (Esoméprazole 40mg X 2/ d) - amoxicillin 1gX2 / d- levofloxacin 500mg X2 / d The total duration of treatment is 14 days.	Other: Triple therapy guided by the result of the molecular resistance test; Triple therapy guided by the result of the molecular resistance test: If clarithromycin S : high dose PPI (Esoméprazole 40mg X 2/ d) - amoxicillin 1gX2 / d - clarithromycin 500mgX2 / d The total duration of treatment is 14 days.; If clarithromycin R: high dose PPI (Esoméprazole 40mg X 2/ d) - amoxicillin 1gX2 / d- levofloxacin 500mg X2 / d The total duration of treatment is 14 days.; Other Names: therapeutic procedure
Active Comparator: Quadruple concomitant therapy; high dose PPI (Esoméprazole 40 mg X 2 / d- amoxicillin 1gX2 / d - - clarithromycin 500mgX2 / d - metronidazole 500mgX2 / d for 14 days	Other: Quadruple concomitant therapy treatment; Quadruple concomitant therapy treatment: high dose PPI (Esoméprazole 40 mg X 2 / d- amoxicillin 1gX2 / d - - clarithromycin 500mgX2 / d - metronidazole 500mgX2 / d for 14 days; Other Names: therapeutic procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate on the basis of a negative C13 - urea breath test done 6-12 weeks after the end of treatment	Eradication rates will be compared between the patients allocated to standard treatment currently recommended (quadruple concomitant treatment, control group) and patients allocated to triple therapy chosen according to the results of molecular detection of clarithromycin resistance (guided triple therapy,, test group). The breath test is recognized as a sensitive and specific test for infection with H. pylori, particularly in the context of monitoring the efficacy of treatment. It will be carried out blindly to allocated group.	at 34 month

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety criteria will include all adverse events occurring in the two treatment groups	at 34 month

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Jean-Charles Delchier, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Anticipated): February 1, 2019
• Study Completion (Anticipated): March 1, 2019

Study Registration Dates

• First Submitted: September 30, 2015
• First Submitted That Met QC Criteria: October 14, 2015
• First Posted (Estimate): October 15, 2015

Study Record Updates

• Last Update Posted (Actual): July 5, 2017
• Last Update Submitted That Met QC Criteria: July 3, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Endoscopy; Urea breath test; Naïve patient; Suspicion of H pylori infection; Antibiotics therapeutic strategies
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: P140928; 2015-A00457-42 (Other Identifier: IDRCB)