Clinical trial NCT01273441: Study Comparing Sequential and Concomitant Therapy for Helicobacter Pylori Eradication in Routine Clinical Practice
Official title: Phase 4, Prospective, Randomized and Comparative Study Comparing Sequential and Concomitant Therapy for Helicobacter Pylori Eradication in Routine Clinical Practice
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Helicobacter Pylori
Lead sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Sponsor class: OTHER
First posted: 2011-01-10
Enrollment: 338
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: Helicobacter pylori is the main cause of chronic gastritis, peptic ulcer and gastric tumors (adenocarcinoma and lymphoma). 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. The usually recommended pattern in the consensus conferences 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. Recent meta-analyses have that the current global eradication rate after standard triple therapy is less than 80%. Several European studies have found even lower eradication rates, with 35-40% of cases resulting in treatment failure. Treatment failure leads to a second treatment and a new diagnostic test to confirm eradication.

Detailed description: Justification of the study:

One of the latest therapeutic innovations is sequential therapy, introduced in Italy by Zullo et al. The drug delivery strategy 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. Sequential therapy has proved more effectiveness than standard triple therapy for seven and ten days. In order to assess the efficacy of this new treatment in our area, over the past year we conducted a multicentre observational pilot study in routine clinical practice conditions in patients infected with H. pylori and with indications for eradication. 139 patients from 6 different centres were included. Excellent treatment compliance and minimal side effects, similar to those described with triple therapy, were shown. The results confirm similar efficacy to that obtained in previous studies and an eradication rate significantly higher than that obtained with classic triple therapy in our area.

Several previous studies have shown excellent efficacy of quadruple therapy with a PPI, amoxicillin, clarithromycin and metronidazole, administering "concomitantly" the same drugs as those of sequential therapy, but only for 5-7 days. Several studies have found a higher eradication rate of this "concomitant" therapy as compared with classic triple therapy. The results of a randomized study in which sequential and concomitant therapy were compared have recently been reported in the American Congress of Gastroenterology. Eradication and adverse events rates were similar with both treatments. This data suggest that the "sequentially"administration of these drugs probably complicated unnecessarily the treatment.

Therefore it is necessary to make a controlled clinical trial to directly compare "sequential" versus "concomitant" therapy. The results of this study will conclude which should be the first line treatment for H. pylori eradication.

Eligibility criteria: Inclusion Criteria:

* Inclusion of 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

Primary outcomes:
measure: "Intention to treat" eradication rates
timeFrame: One year
Secondary outcomes:
measure: "Per protocol" Eradication rate
timeFrame: One year
measure: Compliance
timeFrame: One year
measure: Adverse events
timeFrame: One year
measure: Clinical and demographic variables
timeFrame: One year
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Gijón
country: Spain
facility: Hospital de Cabueñes
city: Huesca
country: Spain
facility: Hospital San Jorge
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Málaga
country: Spain
facility: Hospital Costa del Sol
city: Sabadell
country: Spain
facility: Hospital de Sabadell
city: Sevilla
country: Spain
facility: Hospital Universitario de Valme
city: Terrassa
country: Spain
facility: Hospital Mútua de Terrassa
city: Valladolid
country: Spain
facility: Hospital Universitario Río Hortega
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario "Lozano Blesa"
Study officials:
affiliation: Digestive Service, Hospital Universitario de La Princesa
name: Javier P. Gisbert, Physician Doctor
role: PRINCIPAL_INVESTIGATOR
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