An Open-Label Trial Of Reduced- Dose Pylera, Amoxicillin, and Esomeprazole in the Treatment Of Helicobacter Pylori Infection
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|ClinicalTrials.gov Identifier: NCT02045251|
Recruitment Status : Withdrawn (Unavailability of clarithromycin 250 mg in the market)
First Posted : January 24, 2014
Last Update Posted : January 15, 2015
|First Submitted Date ICMJE||July 18, 2013|
|First Posted Date ICMJE||January 24, 2014|
|Last Update Posted Date||January 15, 2015|
|Study Start Date ICMJE||June 2013|
|Estimated Primary Completion Date||July 2016 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Helicobacter pylori eradication [ Time Frame: Eradication ]
The rate of eradication of H. pylori using the proposed regimen
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT02045251 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Side effects of treatment [ Time Frame: Day 10 (at the end of treatment) ]
Assessment of side effects of the new regimen
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||An Open-Label Trial Of Reduced- Dose Pylera, Amoxicillin, and Esomeprazole in the Treatment Of Helicobacter Pylori Infection|
|Official Title ICMJE||AN OPEN-LABEL TRIAL OF REDUCED- DOSE PYLERA (BISMUTH, METRONIDAZOLE, TETRACYCLINE), AMOXICILLIN, AND ESOMEPRAZOLE IN THE TREATMENT OF HELICOBACTER PYLORI INFECTION|
Over the years, it has become clear that the first-line triple therapy is losing efficacy worldwide. A capsule containing 3 agents (Pylera®) containing 125mg metronidazole, 140mg bismuth subcitrate potassium, and 125mg tetracycline was made available.
The efficacy of the Pylera capsule was studied in a randomized control trial, in which a quadruple Pylera therapy (Pylera capsule and a PPI) was evaluated against the standard triple regimen. In the study, 3 three-in-one capsules were taken four times daily (after meals and at bedtime).
Given the above, we aim at assessing the effectiveness of fewer pills per day of the Pylera capsule (3 Pylera capsules supplemented with the addition of amoxicillin and esomeprazole twice daily; sum of 10 pills/day for 10 days) in the eradication of H. pylori.
Infection with H. pylori has been linked with chronic active gastritis, peptic ulcer disease, adenocarcinoma and Non-Hodgkin's lymphoma of the stomach. Eradication of this organism has been recommended for patients with peptic ulcer disease, low-grade gastric mucosa-associated lymphoid tissue lymphoma, atrophic gastritis, unexplained iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, as well as first-degree relatives of gastric cancer patients. Guidelines still recommend using triple therapy regimen of PPI, clarithromycin and amoxicillin/metronidazole twice daily for 7 to 14 days. Over the years, it has become clear that the first-line triple therapy is losing efficacy worldwide with per protocol (PP) and intent-to-treat (ITT) eradication rates of less than 80%. In light of the low eradication rates of this regimen, quadruple regimens (bismuth and non bismuth based) or alternative fluoroquinolones-based regimens evolved in an attempt to increase the eradication of H. pylori. Most of the new quadruple regimens are clarithromycin-based. Quadruple therapies improved eradication rates to 85-90% but the increasing resistance of H. pylori to clarithromycin rendered the above-mentioned regimens suboptimal. Many attempts to increase the number of antibiotics in treatment regimens were faced with intolerability by patients of the large number of pills and increasing side effects (metallic taste, nausea, etc.). Considering the above, a capsule containing 3 agents (Pylera®) containing 125mg metronidazole, 140mg bismuth subcitrate potassium, and 125mg tetracycline was made available. The importance of such capsule lies in the 3 in 1 packaging and in the avoidance of clarithromycin use and hence the low risk of resistance. The efficacy of the Pylera capsule was studied in a randomized control trial, in which a quadruple Pylera therapy (Pylera capsule and a PPI) was evaluated against the standard triple regimen. In the study, 3 three-in-one capsules were taken four times daily (after meals and at bedtime). An omeprazole capsule was taken with the three single three-in-one capsules after morning and evening meals. Quadruple therapy (Pylera-based) provided superior eradication rates when compared to the standard triple therapy (as high as 80% eradication rate versus 55% on ITT) with similar safety and tolerability . In the aforementioned study, patients on quadruple therapy were taking the sum of 14 pills per day. This big number of pills per day is too high and may threaten compliance and adherence in real life situations outside of controlled clinical trials. This is evidenced by the difference in the PP and ITT eradication rates (93% and 80% respectively) that can be attributed to the load of pill load.
The sensitivity of H. pylori to tetracycline and amoxicillin is very high and resistance is approximately zero . Our local data in Lebanon show essentially no resistance to tetracycline or amoxicillin and a modest rate of metronidazole resistance, similar to Western countries (Fig 1). The use of these antibiotics to treat H. pylori infection is promising. In addition, we have recently shown in 2 separate randomized controlled trials that the reduced or half-dose of antibiotics (including 500 mg bid of amoxicillin and 250 mg bid of metronidazole) can achieve the same eradication of H. pylori at reduced cost and reduced side effects.
Fig 1. In vitro Susceptibility of H. Pylori in Lebanon. Sharara AI, et al. Int J Antimicrob Agents 2000; 19:155-8.
Our studies have shown a declining rate of H. pylori eradication with conventional triple therapy over time (Fig2).
Fig 2. 10-day Legacy Triple Therapy in Lebanon. Soweid A, et al. ACG 2005 [abstract]; Mansour N, et al, Sharara AI. Eur J Gastroenterol Hepatol 2011
Given the above, we aim at assessing the effectiveness of fewer pills per day of the Pylera capsule (3 Pylera capsules supplemented with the addition of amoxicillin and esomeprazole twice daily; sum of 10 pills/day for 10 days) in the eradication of H. pylori. The total dose of drugs is shown in Figure 3.
One hundred patients from the outpatient department and the endoscopy unit at AUBMC will be enrolled in this open-label single arm trial. Patients with positive CLO tests or urea breath tests, or histological documentation of H. pylori infection, will be enrolled in the study. The patients will be followed up by phone calls on day 10 for side effects and for pill count. Patients will be assessed for the presence of these side effects at the end of the treatment (Day 10). A urea breath test will be done for all patients after ≥ 4 weeks of therapy completion and a minimum of 2 weeks of PPI therapy to evaluate eradication rates
Eradication rate will be assessed periodically (every 10 patients) to confirm efficacy with stop points as follows:
Patients 1-10: <60% eradication Patients 1-20: <65% eradication Patients 1-30: <70% eradication Patients 1-40: <75%eradication Patients 1-50: <80% eradication
Fig 3. Doses of drugs of the proposed Pylera regimen compared to the previously studied full-dose and half-dose quadruple (non-bismuth based) regimens.
The objective of this study is to evaluate the efficacy of the 4 tablets (2 capsules containing metronidazole, bismuth, and tetracycline) plus amoxicillin and esomeprazole) given twice a day for 10 days in the eradication of H. pylori. The primary end point is H. pylori eradication rate on ITT and PP analysis. Secondary endpoints include: (1) tolerability, (2) adverse events of the drug regimen, (3) and cost.
B- Patient population:
One hundred patients from the outpatient department and the endoscopy unit at AUBMC will be enrolled in this open-label trial.
C- Design and methods:
After documentation of the H. pylori infection, the primary physician will introduce the patient to the research fellow who will give to the patients a clear explanation of the purpose of the study, risks, and benefits. Those who agree to participate and sign the informed consent will be enrolled in our study. All patients will take the treatment for ten days. The patients will be assessed for side effects on days 5 and 10 of the treatment regimen. The eradication rate will be assessed periodically (every 10 patients for the first 50 patients) for efficacy and the study will be stopped if the target rates are not met. The Pylera tablets will be provided free to patients. However, the amoxicillin and esomeprazole are not provided freely.
Patients will be taking:
Compliance and potential side effects will be evaluated by phone calls (day 10) during and shortly after the treatment period. After a minimum of 4 weeks of therapy completion, patients will be asked to present for a urea breath test free of charge in order to evaluate the eradication rate of H. pylori. All patients should be off any PPI for at least two weeks before testing.
D- Statistical Interpretation:
Efficacy of eradication of each group will be evaluated directly from the quotient of the patients with negative urea breath test over the total number of patients enrolled in that group. Success of therapy will be evaluated according to intent-to treat and per-protocol analyses.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 4|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Treatment of H. Pylori Infection|
|Intervention ICMJE||Drug: Pylera based reduced regimen
Patients with H. pylori infection will be treated with a 10 day course of reduced Pylera based regimen.
|Study Arms ICMJE||Experimental: Interventional Arm
This arm will have 100 patients receiving the proposed Pylera based regimen for 10 days.
Intervention: Drug: Pylera based reduced regimen
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Estimated Study Completion Date ICMJE||September 2016|
|Estimated Primary Completion Date||July 2016 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Patients with either positive CLO tests, urea breath tests, or histopathologic documention of H. pylori infection, and agreeing to the study by signing the informed consent.
|Ages ICMJE||18 Years to 80 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Lebanon|
|Removed Location Countries|
|NCT Number ICMJE||NCT02045251|
|Other Study ID Numbers ICMJE||IM.AS1.33|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||American University of Beirut Medical Center|
|Study Sponsor ICMJE||American University of Beirut Medical Center|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||American University of Beirut Medical Center|
|Verification Date||March 2013|
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