14-day Quadruple Hybrid vs. Concomitant Therapies for Helicobacter Pylori Eradication

Sponsor

Infante, Javier Molina, M.D. (Other)

Overall Status

Unknown status

CT.gov ID

NCT01464060

Collaborator

(none)

400

Enrollment

Locations

Arms

Duration (Months)

100

Patients Per Site

6.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Helicobacter pylori (H. pylori) infects approximately 50% of the adult population and is well recognized as the main cause of gastritis, peptic ulcer disease and gastric cancer. The cure of the H. pylori infection prevents recurrence of duodenal and gastric ulcer and improves dyspepsia in a significant proportion of cases, so it is cost-effective.

Eradication therapy has changed over time. Recent meta-analyses have that the current global eradication rate after standard triple therapy (STT) is less than 80%. Several European studies have found even lower eradication rates, with 35-40% of cases resulting in treatment failure, probably due to increased resistance to antibiotics in many geographical areas, principally to clarithromycin. The usually recommended pattern in the American and European (Maastricht III) consensus conferences from 2007 has traditionally been triple therapy, composed by the combination of 2 antibiotics (clarithromycin plus amoxicillin or metronidazole) and a proton pump inhibitor (PPI) for 7-14 days. However, triple therapy was discouraged in settings with high rates of clarithromycin resistance (15-20%) and, as such, new strategies in order to improve the efficacy of first-line treatments are required. Treatment failure increases antibiotic resistant strains, leads to a second treatment and a new diagnostic test to confirm eradication. Unfortunately, it remains unknown whether there is room for improvement in these geographical areas using clarithromycin-containing therapies or switching to bismuth quadruple therapy should be followed instead.

Condition or Disease	Intervention/Treatment	Phase
Helicobacter Pylori Infection	Drug: PPI, amoxicillin, metronidazole and clarithromycin Drug: PPI, amoxicillin, metronidazole and clarithromycin	Phase 4

Detailed Description

Justification of the study:

Several non-bismuth quadruple clarithromycin-containing regimens have raised over the last decade aiming to substitute standard triple therapy (STT) for first-line H. pylori eradication therapy. Sequential therapy, introduced in Italy, involves a 5-day induction phase with dual therapy (a PPI every 12 hours and amoxicillin 1g every 12 hours), followed immediately by triple therapy for 5 days with a PPI every 12 hours, metronidazole 500 mg every 12 hours and clarithromycin 500 mg every 12 hours. 10-day sequential therapy proved more effectiveness than STT with excellent treatment compliance and minimal side effects. However, the efficacy of sequential therapy seems to be notably impaired by clarithromycin resistance and dual clarithromycin and metronidazole resistance, which is becoming a common scenario in developed countries.

Other interesting and resurfaced therapeutic alternative is the non-bismuth quadruple therapy (NBQT), also called "concomitant" therapy, which includes a PPI, amoxicillin, clarithromycin and a nitroimidazole, all drugs given concurrently and twice daily. It has also demonstrated its superiority over STT and it could be potential replacement for STT as first-line regimen. However, NBQT might have several advantages over sequential therapy, namely, less complexity for both the patient and the physician, twice the duration of all prescribed antibiotics, a proper validation process worldwide and a higher efficacy over sequential therapy for both clarithromycin and dual-resistant H. pylori. Finally, another recent innovation is the 14-day quadruple clarithromycin-based regimen, so-called the sequential-concomitant "hybrid" therapy, which involves PPI and amoxicillin for 7 days plus a 7-day course of NBQT. Outstanding cure rates close to 100% have been recently reported using this scheme, thereby requiring further consideration.

Therefore it is necessary to make a controlled clinical trial to directly compare NBQT "hybrid" versus "concomitant" therapy in settings with documented high clarithromycin resistance rates. In order to maximize the efficacy of eradication regimens, it would be necessary to extend duration to 14 days and using high-dose PPI (omeprazole 40 mg bid). The results of this study will conclude whether there is still room for clarithromycin-containing regimens in H. pylori eradication even in settings with high antibiotic resistance rates.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 4, Prospective, Randomized Study Comparing 14-day Non-bismuth Quadruple "Hybrid" and "Concomitant" Therapies for Helicobacter Pylori Eradication in Settings With High Clarithromycin Resistance

Study Start Date :

Sep 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2012

Anticipated Study Completion Date :

Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: "Hybrid" therapy Dual therapy for 7 days: 40 mg omeprazole and 1g amoxicillin every 12h. After dual therapy continue with a quadruple therapy for 7 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h.	Drug: PPI, amoxicillin, metronidazole and clarithromycin Dual therapy for 7 days: 40 mg omeprazole and 1g amoxicillin every 12h. After dual therapy continue with a quadruple therapy for 7 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h.
Experimental: "Concomitant" therapy Quadruple therapy for 14 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h	Drug: PPI, amoxicillin, metronidazole and clarithromycin Quadruple therapy for 14 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h

Arm

Intervention/Treatment

Active Comparator: "Hybrid" therapy

Dual therapy for 7 days: 40 mg omeprazole and 1g amoxicillin every 12h. After dual therapy continue with a quadruple therapy for 7 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h.

Drug: PPI, amoxicillin, metronidazole and clarithromycin

Experimental: "Concomitant" therapy

Quadruple therapy for 14 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h

Drug: PPI, amoxicillin, metronidazole and clarithromycin

Quadruple therapy for 14 days: 40 mg omeprazole, 1g amoxicillin, 500 mg metronidazole and 500 mg clarithromycin every 12h

Outcome Measures

Primary Outcome Measures

"Intention to treat" eradication rates [1 year]
"Intention-to-treat" eradication of infection.

Secondary Outcome Measures

" Per protocol" eradication rate [1 year]
" Per protocol" eradication of the infection
Treatment compliance [1 year]
Number of participants with adverse events [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with dyspepsia or peptic gastroduodenal ulcer for whom eradication treatment is indicated.
Requirement of confirmation of the diagnosis of H. pylori infection by at least one positive test out of the following: breath test, histology, rapid urease test or culture.

Exclusion Criteria:

Age less than 18 years.
Advanced chronic disease or any other pathology that prevents attending controls and follow up.
Allergy to any of the antibiotics in the treatment.
Previous gastric surgery
Pregnancy and lactation.
History of alcohol or drug abuse.
Previous eradication treatment.
Consumption of antibiotics or bismuth salts during the last 4 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Azienda Ospedaliera Universitaria	Napoli		Italy
2	Hospital de Merida	Merida	Badajoz	Spain
3	Hospital Virgen del Puerto	Plasencia	Caceres	Spain
4	Hospital San Pedro de Alcantara	Caceres		Spain	10003