Helicobacter Eradication Relief of Dyspeptic Symptoms (HEROES-12)

Dyspeptic Symptoms Evolution After Eradication of Helicobacter Pylori in Patients With Different Endoscopic Findings: a Randomized Double-blind Placebo-controlled Clinical Trial With 12 Months of Follow-up

A double-blind clinical trial investigating if a sub-group of functional dyspeptic patients without any use of NSAID or gastric erosions could have a better evolution of their dyspeptic symptoms after Helicobacter eradication than the placebo control group

Study Overview

• Status: Completed
• Conditions: Functional Dyspepsia
• Intervention / Treatment: Drug: Amoxicillin, Clarythromycin, Omeprazole for ten days

Detailed Description

Objective: investigate if a sub-group of functional dyspeptic patients without any use of NSAID or gastric erosions could have a better evolution of their dyspeptic symptoms after Helicobacter eradication than the placebo control group

Design: A randomized double-blind placebo controlled clinical trial

Inclusion Criteria: Patients with more than 18 years, Functional dyspepsia accordingly Rome III criteria, Helicobacter pylori infection by two diagnostic tests

Exclusion Criteria: No concordance with informed consent; Pregnant woman or breast feeding or no trust anticonceptional method; Structural gastrointestinal abnormalities except gastritis, duodenitis or hiatal hernia; Previous treatment for Helicobacter pylori infection; Previous surgery on esophagus, stomach or duodenum; Hypersensitivity to the drugs in study; Proton pump inhibitor use in the previous 15 days; H2-antagonists use in the previous 07 days; Antibiotics use in the previous 30 days; Patients unable to answer the study questionnaires; Alcohol abuse; Drug use; Serious comorbidities; Biliary colic; Irritable bowel syndrome; Gastroesophageal Reflux Disease

Interventions: amoxicillin, clarythromycin, omeprazole for 10 days

Control: Placebo

Outcomes:

Primary: Proportion of patients with 50% reduction of baseline symptoms score measured by the validated Porto Alegre Dyspeptic Symptoms Questionnaire Secondary: Proportion of patients with 100% reduction of baseline symptoms score measured by the validated Porto Alegre Dyspeptic Symptoms Questionnaire; Need of rescue medication; Median difference of score between groups; Mean SF-36 scores evolution between groups; Lost of productivity measured by WPAI between groups

Visits: screening, baseline, 4, 8, 12 months

Endoscopic evaluation: screening, 12 months

Helicobacter detection methods: urease, histology (3 pathologists) performed at screening and 12 months

• Study Type: Interventional
• Enrollment (Actual): 407
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre

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:

• Patients with more than 18 years
• Functional dyspepsia accordingly Rome III criteria
• Helicobacter pylori infection by two diagnostic tests

Exclusion Criteria:

• No concordance with informed consent
• Pregnant woman or breast feeding or no trust anticonceptional method
• Structural gastrointestinal abnormalities except gastritis, duodenitis or hiatal hernia
• Previous treatment for Helicobacter pylori infection
• Previous surgery on esophagus, stomach or duodenum
• Hypersensitivity to the drugs in study
• Proton pump inhibitor use in the previous 15 days
• H2-antagonists use in the previous 07 days
• Antibiotics use in the previous 30 days
• Patients unable to answer the study questionnaires
• Alcohol abuse
• Drug use
• Serious comorbidities
• Biliary colic
• Irritable bowel syndrome
• Gastroesophageal Reflux Disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Amoxicillin 1000 mg BID, clarythromycin 500 mg BID and Omeprazole 20 mg BID for ten days	Drug: Amoxicillin, Clarythromycin, Omeprazole for ten days; Amoxicillin 1000 mg BID, clarythromycin 500 mg BID for ten days in the experimental group and placebo of Amoxicillin 1000 mg BID and placebo of clarythromycin 500 mg BID in the placebo comparator. Both groups receive omeprazole 20 mg bid for 10 days.
PLACEBO_COMPARATOR: 2; Placebo of Amoxicillin 1000 mg BID, placebo of clarythromycin 500 mg BID and Omeprazole 20 mg BID for ten days	Drug: Amoxicillin, Clarythromycin, Omeprazole for ten days; Amoxicillin 1000 mg BID, clarythromycin 500 mg BID for ten days in the experimental group and placebo of Amoxicillin 1000 mg BID and placebo of clarythromycin 500 mg BID in the placebo comparator. Both groups receive omeprazole 20 mg bid for 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with 50% reduction of baseline symptoms score measured by the validated Porto Alegre Dyspeptic Symptoms Questionnaire	the last visit among the antecipated visits (4, 8 and 12 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with 100% reduction of baseline symptoms score measured by the validated Porto Alegre Dyspeptic Symptoms Questionnaire	the last visit among the antecipated visits (4, 8 and 12 months)
Need of rescue medication	4, 8 and 12 months
Median difference of score between groups	the last visit among the antecipated visits (4, 8 and 12 months)
Mean SF-36 scores evolution between groups	12 months
Lost of productivity measured by WPAI between groups	12 months
Adverse Events	4 , 8 and 12 months

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Collaborators: Aché Laboratórios Farmacêuticos Ltda
• Investigators: Principal Investigator: Luiz E Mazzoleni, MD, MsC, PhD, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul; Study Chair: Carlos F Francesconi, MD, PhD, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul; Study Chair: Guilherme B Sander, MD, MsC, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul

Publications and helpful links

General Publications

• Mazzoleni LE, Sander GB, Ott EA, Barros SG, Francesconi CF, Polanczyk CA, Wortmann AC, Theil AL, Fritscher LG, Rivero LF, Cartell A, Edelweiss MI, Uchoa DM, Prolla JC. Clinical outcomes of eradication of Helicobacter pylori in nonulcer dyspepsia in a population with a high prevalence of infection: results of a 12-month randomized, double blind, placebo-controlled study. Dig Dis Sci. 2006 Jan;51(1):89-98. doi: 10.1007/s10620-006-3090-6.
• Ott EA, Mazzoleni LE, Edelweiss MI, Sander GB, Wortmann AC, Theil AL, Somm G, Cartell A, Rivero LF, Uchoa DM, Francesconi CF, Prolla JC. Helicobacter pylori eradication does not cause reflux oesophagitis in functional dyspeptic patients: a randomized, investigator-blinded, placebo-controlled trial. Aliment Pharmacol Ther. 2005 May 15;21(10):1231-9. doi: 10.1111/j.1365-2036.2005.02461.x.
• Sander GB, Mazzoleni LE, Francesconi CF, Wortmann AC, Ott EA, Theil A, Da Cruz PV, Da Silva AC, Oliveira L, Beheregaray S, Matioti S, Somm G, Goldim JR. Development and validation of a cross-cultural questionnaire to evaluate nonulcer dyspepsia: the Porto Alegre Dyspeptic Symptoms Questionnaire (PADYQ). Dig Dis Sci. 2004 Nov-Dec;49(11-12):1822-9. doi: 10.1007/s10620-004-9578-z.
• Mazzoleni LE, Sander GB, Francesconi CF, Mazzoleni F, Uchoa DM, De Bona LR, Milbradt TC, Von Reisswitz PS, Berwanger O, Bressel M, Edelweiss MI, Marini SS, Molina CG, Folador L, Lunkes RP, Heck R, Birkhan OA, Spindler BM, Katz N, Colombo Bda S, Guerrieri PP, Renck LB, Grando E, Hocevar de Moura B, Dahmer FD, Rauber J, Prolla JC. Helicobacter pylori eradication in functional dyspepsia: HEROES trial. Arch Intern Med. 2011 Nov 28;171(21):1929-36. doi: 10.1001/archinternmed.2011.533.
• Sander GB, Mazzoleni LE, Francesconi CF, Balbinotto G, Mazzoleni F, Wortmann AC, Cardoso Ide Q, Klamt AL, Milbradt TC; Helicobacter Eradication Relief of Dyspetic Symptoms Trial Investigators. Influence of organic and functional dyspepsia on work productivity: the HEROES-DIP study. Value Health. 2011 Jul-Aug;14(5 Suppl 1):S126-9. doi: 10.1016/j.jval.2011.05.021.

Helpful Links

• Official Homepage of Site that is Conducting the Study

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (ACTUAL): June 1, 2009
• Study Completion (ACTUAL): June 1, 2009

Study Registration Dates

• First Submitted: November 27, 2006
• First Submitted That Met QC Criteria: November 27, 2006
• First Posted (ESTIMATE): November 28, 2006

Study Record Updates

• Last Update Posted (ACTUAL): March 1, 2018
• Last Update Submitted That Met QC Criteria: February 27, 2018
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Helicobacter pylori; functional dyspepsia; Anti-Inflammatory Agents, Non-Steroidal; Gastritis
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Amoxicillin; Clarithromycin; Omeprazole
• Other Study ID Numbers: 05-422