Helicobacter Infections
Conditions
Keywords
H. Pylori, Quadruple therapy, Eradication rate, Multinational trial, Resistance to antibiotics, Subjects with confirmed Helicobacter Pylori infection
Brief summary
This study aims at evaluating efficacy and safety of quadruple therapy (bismuth, metronidazole, tetracycline and omeprazole: OBMT) vs triple therapy (amoxicillin, clarithromycin and omeprazole: OAC) in H. Pylori eradication. It is hypothesized that quadruple therapy will be comparable in efficacy to triple therapy. Subjects with confirmed H. pylori positive status will be randomized to one of the treatments described above. At week 6 and 10 follow-up visits, a urea breath test (UBT) will be performed to confirm eradication.
Detailed description
The study will include three phases: screening, treatment and follow-up. Screening: this phase will last a maximum of 30 days and subjects eligibility will be evaluated after informed consent signature. Endoscopy and Urea Breath test will be performed in addition to the baseline routine evaluations. Treatment: Subjects assigned to OAC will be treated for 7 days. Those assigned to Pylera will be treated for 10 days. A randomization visit will take place on Day 0 and an end-of-treatment visit will take place between day 8 and 14. Follow-up: includes two visits. approximately one and two months post-treatment. Eradication of H. Pylori will be confirmed through UBT, and resistance will be evaluated in case of treatment failure. These subjects will undergo an endoscopy.
Interventions
Triple therapy given for 7 days at a dose of omeprazole 20 mg BID, amoxicillin 500 mg 2 capsules BID, and clarithromycin 500 mg 1 tablet BID
Pylera is a three in one capsule containing bismuth subcitrate potassium 120 mg, metronidazole 125 mg and tetracycline 125 mg given as 3 capsules QID, with omeprazole 20 mg BID.
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Positive H. Pylori status; * Presence of upper gastro-intestinal symptoms; * Mental and legal ability to sign informed consent.
Exclusion criteria
* Previous surgery of the GI tract; * Clinically significant impairment of renal or hepatic function; * Severe unstable cardiovascular, pulmonary or endocrine disease; * Barrett's oesophagus or high-grade dysplasia; * Dysphagia or vomiting as major symptoms.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Helicobacter Pylori Eradication Confirmed by Urea Breath Test | Week 6 and week 10 follow-up visits | H. pylori Eradication defined as a negative C13-UBT (urea breath test) result at both Week 6 and Week 10 follow-up visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| H. Pylori Eradication and Presence or Past History of Peptic Ulcers | Week 6 and week 10 follow-up visits | Eradication rates in the subset of patients with peptic ulcer (current or past history) at baseline are reported based on the per protocol population. Eradication must be confirmed at week 6 and week 10 by a negative Urea Breath Test conducted within the allocated windows. |
| Clarithromycin Resistance | Measured at baseline | Eradication rates in subset of patients infected with a bacterial strain confirmed as resistant to clarithromycin at baseline. Resistance to clarithromycin defined as Minimum Inhibitory Concentration (MIC) of 1 ug/ml and above |
| Number of Patients Experiencing Treatment Emergent Adverse Events. | at the end of treatment (day 8-14), week 6 and wek 10 follow-up visits. | A treatment-emergent adverse event is defined as an event not present prior to exposure to the study medication or any event already present that worsens in either intensity or frequency following exposure to study medication up to 30 days after study discontinuation. All safety analysis based on the safety population. |
| Overall Compliance to Study Medications | At the end of the treatment phase (days 8-14) | Overall compliance: number of capsules dispensed - number of capsules returned/Number of prescribed capsules X 100. Percentages based on safety population |
| Number of Patients With Bismuth Plasma Concentrations Above the Toxic Level | Baseline (both arms), end of treatment (Day 11-14) and end of study (Day 70) OBMT arm only | Tolerability of OBMT with respect to plasma bismuth concentrations: number of patients with bismuth concentrations above the toxic level (50 ug per liter) |
| Metronidazole Resistance | Measured at baseline | Eradication rates in subset of patients infected with a bacterial strain confirmed as resistant to metronidazole at baseline. Resistance to metronidazole defined as Minimum Inhibitory Concentration (MIC) above 8 ug/ml |
Countries
United Kingdom
Participant flow
Recruitment details
First patient in: 11 June 2008 Last patient out: 22 June 2009 Patients were recruited from clinics and hospitals located in seven European Countries: Germany, Poland, Italy, France, Ireland, Spain, United Kingdom.
Pre-assignment details
If patient was on any contraindicated medications, such as H2 antagonists, sucralfate, or proton pump inhibitors, a washout period of 2 weeks began following informed consent signature, and patient returned to the clinic to perform the endoscopy and the C-13 UBT. Presence of H. pylori needed to be confirmed by C-13 UBT and RUT at least.
Participants by arm
| Arm | Count |
|---|---|
| Quadruple Therapy (OBMT) 10 Days Omeprazole 20 mg BID (twice a day), and the 3 in 1 capsule, Pylera, containing Bismuth Subcitrate potassium 140 mg, metronidazole 125 mg and tetracycline 125 mg, administered as 3 capsules QID (four times day) | 218 |
| Triple Therapy (OAC) 7 Days Omeprazole 20 mg BID, Amoxicillin 500 mg 2 capsules BID and Clarithromycin 500 mg 1 tablet BID | 222 |
| Total | 440 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Investigator Sponsor Judgement | 0 | 1 |
| Overall Study | Lost to Follow-up | 5 | 7 |
| Overall Study | not compliant with study drug/visit | 2 | 3 |
| Overall Study | Protocol Violation | 2 | 7 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Quadruple Therapy (OBMT) 10 Days | Triple Therapy (OAC) 7 Days | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 34 Participants | 28 Participants | 62 Participants |
| Age, Categorical Between 18 and 65 years | 184 Participants | 194 Participants | 378 Participants |
| Age, Continuous | 48.53 years STANDARD_DEVIATION 14.64 | 47.95 years STANDARD_DEVIATION 14.52 | 48.24 years STANDARD_DEVIATION 14.58 |
| Region of Enrollment France | 15 participants | 17 participants | 32 participants |
| Region of Enrollment Germany | 92 participants | 91 participants | 183 participants |
| Region of Enrollment Italy | 10 participants | 10 participants | 20 participants |
| Region of Enrollment Poland | 91 participants | 93 participants | 184 participants |
| Region of Enrollment Spain | 7 participants | 6 participants | 13 participants |
| Region of Enrollment United Kingdom | 3 participants | 5 participants | 8 participants |
| Sex: Female, Male Female | 105 Participants | 100 Participants | 205 Participants |
| Sex: Female, Male Male | 113 Participants | 122 Participants | 235 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 98 / 216 | 105 / 222 |
| serious Total, serious adverse events | 4 / 216 | 3 / 222 |
Outcome results
Primary
Helicobacter Pylori Eradication Confirmed by Urea Breath Test
H. pylori Eradication defined as a negative C13-UBT (urea breath test) result at both Week 6 and Week 10 follow-up visits.
Time frame: Week 6 and week 10 follow-up visits
Population: No imputation method used, as this is the per protocol population, which excludes patients with missing values, or with protocol violations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadruple Therapy (OBMT) 10 Days | Helicobacter Pylori Eradication Confirmed by Urea Breath Test | 166 Participants |
| Triple Therapy (OAC) 7 Days | Helicobacter Pylori Eradication Confirmed by Urea Breath Test | 112 Participants |
Secondary
Clarithromycin Resistance
Eradication rates in subset of patients infected with a bacterial strain confirmed as resistant to clarithromycin at baseline. Resistance to clarithromycin defined as Minimum Inhibitory Concentration (MIC) of 1 ug/ml and above
Time frame: Measured at baseline
Population: Per protocol analysis population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadruple Therapy (OBMT) 10 Days | Clarithromycin Resistance | 30 participants |
| Triple Therapy (OAC) 7 Days | Clarithromycin Resistance | 2 participants |
Secondary
H. Pylori Eradication and Presence or Past History of Peptic Ulcers
Eradication rates in the subset of patients with peptic ulcer (current or past history) at baseline are reported based on the per protocol population. Eradication must be confirmed at week 6 and week 10 by a negative Urea Breath Test conducted within the allocated windows.
Time frame: Week 6 and week 10 follow-up visits
Population: Per protocol population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadruple Therapy (OBMT) 10 Days | H. Pylori Eradication and Presence or Past History of Peptic Ulcers | 18 Participants |
| Triple Therapy (OAC) 7 Days | H. Pylori Eradication and Presence or Past History of Peptic Ulcers | 15 Participants |
Secondary
Metronidazole Resistance
Eradication rates in subset of patients infected with a bacterial strain confirmed as resistant to metronidazole at baseline. Resistance to metronidazole defined as Minimum Inhibitory Concentration (MIC) above 8 ug/ml
Time frame: Measured at baseline
Population: Per protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadruple Therapy (OBMT) 10 Days | Metronidazole Resistance | 38 participants |
| Triple Therapy (OAC) 7 Days | Metronidazole Resistance | 28 participants |
Secondary
Number of Patients Experiencing Treatment Emergent Adverse Events.
A treatment-emergent adverse event is defined as an event not present prior to exposure to the study medication or any event already present that worsens in either intensity or frequency following exposure to study medication up to 30 days after study discontinuation. All safety analysis based on the safety population.
Time frame: at the end of treatment (day 8-14), week 6 and wek 10 follow-up visits.
Population: Safety population, described as all randomized patients having received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadruple Therapy (OBMT) 10 Days | Number of Patients Experiencing Treatment Emergent Adverse Events. | 101 Participants |
| Triple Therapy (OAC) 7 Days | Number of Patients Experiencing Treatment Emergent Adverse Events. | 112 Participants |
Secondary
Number of Patients With Bismuth Plasma Concentrations Above the Toxic Level
Tolerability of OBMT with respect to plasma bismuth concentrations: number of patients with bismuth concentrations above the toxic level (50 ug per liter)
Time frame: Baseline (both arms), end of treatment (Day 11-14) and end of study (Day 70) OBMT arm only
Population: Plasma bismuth concentrations were analysed in the OBMT arm only. The goal was to determine whether bismuth plasma concentrations would be of 50 ug/l or above at end of treatment, or at the end of study. The results report the number of patients having reached 50 ug/l in the OBMT arm at either of these timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadruple Therapy (OBMT) 10 Days | Number of Patients With Bismuth Plasma Concentrations Above the Toxic Level | 0 participants |
Secondary
Overall Compliance to Study Medications
Overall compliance: number of capsules dispensed - number of capsules returned/Number of prescribed capsules X 100. Percentages based on safety population
Time frame: At the end of the treatment phase (days 8-14)
Population: Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quadruple Therapy (OBMT) 10 Days | Overall Compliance to Study Medications | 97.58 participants | Standard Deviation 10.71 |
| Triple Therapy (OAC) 7 Days | Overall Compliance to Study Medications | 97.47 participants | Standard Deviation 14.91 |