Ignite Creation Date:
2024-05-06 @ 9:20 AM
Last Modification Date:
2024-10-26 @ 12:13 PM
Study NCT ID:
NCT02959255
Status:
COMPLETED
Last Update Posted:
2018-03-29
First Post:
2016-11-07
Brief Title:
10-day Versus 14-day Concomitant PAMC as First-line Treatment Strategy for the Eradication of H Pylori Infection
Sponsor:
Elpen Pharmaceutical Co Inc
Organization:
Elpen Pharmaceutical Co Inc
Study Overview
Official Title:
A Greek Single Center Randomized Double Blind Controlled Clinical Study Comparing the 10-day Versus the 14-day Concomitant Proton Pump Inhibitor PPI Amoxicillin Metronidazole Clarithromycin PAMC Therapeutic Scheme as First-line Treatment Strategy for the Eradication of H Pylori Infection
Status:
COMPLETED
Status Verified Date:
2018-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Helicobacter pylori H pylori infection is highly associated with gastrointestinal disorders including peptic ulcer disease gastric cancer and gastric mucosa associated lymphoid tissue lymphoma1 In 1994 H pylori was classified as a group carcinogen by the International Agency for Research on Cancer Since then many consensus conferences and clinical guidelines worldwide have been established for the treatment of H pylori infection
Despite H pylori infecting an estimated 50 of the global populationthere is no universally effective regimen in everyday clinical practice The current European Helicobacter Study Group Guidelines for the first line empirical treatment of the H pylori infection propose a variety of treatment strategies as optimal treatment of H pylori infection requires careful attention to local antibiotic resistance and eradication patterns Most recently the Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults strongly recommended that all H pylori eradication regimens now be given for 14 days Recommended first-line strategies include concomitant nonbismuth quadruple therapy proton pump inhibitor PPI amoxicillin metronidazole clarithromycin PAMC and traditional bismuth quadruple therapy PPI bismuth metronidazole tetracycline PBMTThe aforementioned statement by an international working group of specialists chosen by the Canadian Association of Gastroenterology is of the outmost importance especially in countries with increased antibiotic resistance like Greece with resistance rates 20 to clarithromycin and 40 to metronidazole
Despite H pylori infecting an estimated 50 of the global populationthere is no universally effective regimen in everyday clinical practice The current European Helicobacter Study Group Guidelines for the first line empirical treatment of the H pylori infection propose a variety of treatment strategies as optimal treatment of H pylori infection requires careful attention to local antibiotic resistance and eradication patterns Most recently the Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults strongly recommended that all H pylori eradication regimens now be given for 14 days Recommended first-line strategies include concomitant nonbismuth quadruple therapy proton pump inhibitor PPI amoxicillin metronidazole clarithromycin PAMC and traditional bismuth quadruple therapy PPI bismuth metronidazole tetracycline PBMTThe aforementioned statement by an international working group of specialists chosen by the Canadian Association of Gastroenterology is of the outmost importance especially in countries with increased antibiotic resistance like Greece with resistance rates 20 to clarithromycin and 40 to metronidazole
Detailed Description:
In Greece while the efficacy of the 10-day concomitant PAMC scheme has been recently establishedto our knowledge no head-to-head comparison evaluating treatment time 10 versus 14 days of the same therapeutic regimen has been tried out We decided to conduct a randomized double blind controlled clinical study comparing the 10-day versus the 14-day concomitant PAMC therapeutic scheme as first-line treatment strategy for the eradication of H pylori infection in a country of increased dual resistance to clarithromycin and metronidazole where bismuth is unavailable The primary end point of our study will be treatment efficacy primary and secondary antibiotic resistance while secondary end points will be patient compliance and safety
This open labeled prospective randomized trial will be held at the Army Share Fund Hospital NIMTS in Athens Greece and will be conducted by the Hospitals Department of Gastroenterology Written informed consent will obtained from all participants before enrollment The study must be approved before hand by the Institutional Review Board of Hospital
Interventions A physician will be recruited so as to obtain the patients demographic data and medical history Using sealed envelopes eligible patients will be randomized in two groups with a research assistant assigning the therapies according to the treatment allocations kept in the envelopes In the first group patients will be assigned to a 10-day concomitant PAMC therapy 40mg esomeprazole twice daily 500mg clarithromycin twice daily 1gr amoxicillin twice daily and 500mg metronidazole twice daily In the second group patients will be assigned to the same concomitant PAMC therapy for 14days Each envelope will contain precise written instructions regarding the treatment schedule dosing and time of medication ingestion while further instructions will be available if needed via the telephone
Follow-up and outcome To confirm compliance all patients will be asked to bring their remaining medication 5 days after the end of the treatment where we will count the rest of their pills Patients with a compliance 80 will be excluded from the study per protocol PP analysis Patients will also be interviewed for reasons responsible for missing any doses of the regimens as well as for the occurrence of any new or worsened medical conditions that led them to seek medical attention Adverse events will be classified as minor or major with the later leading to discontinuation of the treatment
Four weeks after the treatment period with no administration of PPIs or any antibiotics we will confirm H pylori eradication using C13-UBT by a staff member who will be blind to the eradication arm of each patient In case of treatment failure a repeated endoscopy will be performed with biopsy specimens being taken two from the antrum and two from the body of the stomach Biopsy specimens will be cultured and antibiotic susceptibility will be determined for amoxicillin tetracycline clarithromycin metronidazole and levofloxacin with the aid of the agar dilution test according to the standard European protocol1415 The microbiologist who will be performing the agar dilution test will be blinded to the treatment If first-line eradication therapy fails second-line therapy will be administered according to antibiotic susceptibility
Statistical analysis In this study a clinically significant difference for eradication between the two groups will be 15 In order to achieve 80 power for detecting this difference along with an alpha level of 005 and an allocation ratio of 11 we calculated a needed sample of 364 patients Since this is a convenient clinical sample the study will be terminated either by reaching this number of patients or by the studys timeline limitation Baseline characteristics will be compared and the difference of the observed eradication rates between the study groups will be assessed The results of this study will be analyzed in an intention to treat ITT and a PP population The ITT analysis will include all randomized patients who will have taken at least one dose of the study medication regardless of compliance The patients whose infection statuses will be unknown following treatment will be considered treatment failures for the purposes of the ITT analysis The PP analysis will include patients with at least 80 compliance excluding the patients with unknown H pylori status following therapy and those with major protocol violations
This open labeled prospective randomized trial will be held at the Army Share Fund Hospital NIMTS in Athens Greece and will be conducted by the Hospitals Department of Gastroenterology Written informed consent will obtained from all participants before enrollment The study must be approved before hand by the Institutional Review Board of Hospital
Interventions A physician will be recruited so as to obtain the patients demographic data and medical history Using sealed envelopes eligible patients will be randomized in two groups with a research assistant assigning the therapies according to the treatment allocations kept in the envelopes In the first group patients will be assigned to a 10-day concomitant PAMC therapy 40mg esomeprazole twice daily 500mg clarithromycin twice daily 1gr amoxicillin twice daily and 500mg metronidazole twice daily In the second group patients will be assigned to the same concomitant PAMC therapy for 14days Each envelope will contain precise written instructions regarding the treatment schedule dosing and time of medication ingestion while further instructions will be available if needed via the telephone
Follow-up and outcome To confirm compliance all patients will be asked to bring their remaining medication 5 days after the end of the treatment where we will count the rest of their pills Patients with a compliance 80 will be excluded from the study per protocol PP analysis Patients will also be interviewed for reasons responsible for missing any doses of the regimens as well as for the occurrence of any new or worsened medical conditions that led them to seek medical attention Adverse events will be classified as minor or major with the later leading to discontinuation of the treatment
Four weeks after the treatment period with no administration of PPIs or any antibiotics we will confirm H pylori eradication using C13-UBT by a staff member who will be blind to the eradication arm of each patient In case of treatment failure a repeated endoscopy will be performed with biopsy specimens being taken two from the antrum and two from the body of the stomach Biopsy specimens will be cultured and antibiotic susceptibility will be determined for amoxicillin tetracycline clarithromycin metronidazole and levofloxacin with the aid of the agar dilution test according to the standard European protocol1415 The microbiologist who will be performing the agar dilution test will be blinded to the treatment If first-line eradication therapy fails second-line therapy will be administered according to antibiotic susceptibility
Statistical analysis In this study a clinically significant difference for eradication between the two groups will be 15 In order to achieve 80 power for detecting this difference along with an alpha level of 005 and an allocation ratio of 11 we calculated a needed sample of 364 patients Since this is a convenient clinical sample the study will be terminated either by reaching this number of patients or by the studys timeline limitation Baseline characteristics will be compared and the difference of the observed eradication rates between the study groups will be assessed The results of this study will be analyzed in an intention to treat ITT and a PP population The ITT analysis will include all randomized patients who will have taken at least one dose of the study medication regardless of compliance The patients whose infection statuses will be unknown following treatment will be considered treatment failures for the purposes of the ITT analysis The PP analysis will include patients with at least 80 compliance excluding the patients with unknown H pylori status following therapy and those with major protocol violations
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None