Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT02045251 |
| Other study ID # |
IM.AS1.33 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
Phase 4
|
| First received |
July 18, 2013 |
| Last updated |
January 14, 2015 |
| Start date |
June 2013 |
| Est. completion date |
September 2016 |
Study information
| Verified date |
March 2013 |
| Source |
American University of Beirut Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Lebanon: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
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.
Description:
ABSTRACT
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 [1]. 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 [2]. 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.
Study Description:
A- Objective:
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.
- Inclusion criteria 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.
- Exclusion criteria
- Age under 18 or older than 80 years
- Allergies to any of the drugs used
- Recent antibiotic therapy (within 2 weeks of enrollement)
- Severe ulcers or bleeding
- Gastric perforation or obstruction
- Previous gastrectomy
- Gastric cancer
- Pregnancy or lactation
- Prior eradication therapy for H. pylori
- Severe concomitant disease or condition making the treatment unlikely to be
effective i.e. alcoholism, drug addiction, and history of poor compliance.
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:
- 3 Pylera capsules b.i.d (per capsule: 125mg metronidazole, 125mg tetracycline, 140mg
bismuth; i.e. 250mg metronidazole, 250 tetracycline, and 280mg bismuth b.i.d)
- Amoxicillin (Amoxil®) 500 g b.i.d.
- PPI (Esomeprazole 20mg b.i.d)
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.
