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

NCT ID: NCT02576236

Last Updated: 2017-07-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 2500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2019-03-31

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.

Conditions

H Pylori Infection Eradication; Antibiotics Therapeutic Strategies; H Pylori Eradication

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Triple therapy guided by the result of the molecular resistance test

Intervention Type: OTHER

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.

Quadruple concomitant therapy

high dose PPI (Esoméprazole 40 mg X 2 / d- amoxicillin 1gX2 / d - - clarithromycin 500mgX2 / d - metronidazole 500mgX2 / d for 14 days

Group Type: ACTIVE_COMPARATOR

Quadruple concomitant therapy treatment

Intervention Type: OTHER

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

Interventions

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

Intervention Type: 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.

Intervention Type: OTHER

Other Intervention Names

therapeutic procedure; therapeutic procedure

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Charles Delchier, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Henri Mondor Hospital

Créteil, , France

Site Status: RECRUITING

Countries

France

Facility Contacts

Dalila Selmane, CRA

Role: primary

dalila.selmane@aphp.fr

(0)1 49 81 33 86 ext. +33

References

Amiot A, Hacoon J, Heluwaert F, Mion F, Lamarque D, Moussata D, Mimouni M, Delchier JC, Durand-Zaleski I, Audureau E, Bastuji-Garin S; HEPYSE Study Group. 14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial. Helicobacter. 2024 Mar-Apr;29(2):e13076. doi: 10.1111/hel.13076.

Reference Type: DERIVED

PMID: 38680067 (View on PubMed)

Other Identifiers

2015-A00457-42

Identifier Type: OTHER

Identifier Source: secondary_id

P140928

Identifier Type: -

Identifier Source: org_study_id