Efficacy and Safety of Quadruple Therapy in Eradication of H. Pylori: A Comparison to Triple Therapy

This study has been completed.
Sponsor:
Information provided by:
Axcan Pharma
ClinicalTrials.gov Identifier:
NCT00669955
First received: April 29, 2008
Last updated: August 3, 2010
Last verified: August 2010
Results First Received: June 21, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Helicobacter Infections
Interventions: Drug: Omeprazole, amoxicillin, clarithromycin
Drug: Pylera (Bismuth subcitrate potassium, metronidazole, tetracycline) given in combination with omeprazole

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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 urea breath test. Presence of H pylori needed to be confirmed by C-13 UBT and RUT at least.

Reporting Groups
  Description
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)
Triple Therapy (OAC) 7 Days Ompeprazole 20 mg BID, Amoxicilin 500 mg 2 capsules BID and Clarithromycin 500 mg 1 tablet BID

Participant Flow:   Overall Study
    Quadruple Therapy (OBMT) 10 Days     Triple Therapy (OAC) 7 Days  
STARTED     218 [1]   222  
COMPLETED     204     195  
NOT COMPLETED     14     27  
Adverse Event                 3                 5  
Death                 0                 1  
Withdrawal by Subject                 2                 3  
Lost to Follow-up                 5                 7  
Protocol Violation                 2                 7  
Investigator Sponsor Jugement                 0                 1  
not compliant with study drug/visit                 2                 3  
[1] 216 patients received study drug. 2 patients were dispensed study drug but did not take it



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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)
Triple Therapy (OAC) 7 Days Ompeprazole 20 mg BID, Amoxicilin 500 mg 2 capsules BID and Clarithromycin 500 mg 1 tablet BID
Total Total of all reporting groups

Baseline Measures
    Quadruple Therapy (OBMT) 10 Days     Triple Therapy (OAC) 7 Days     Total  
Number of Participants  
[units: participants]
  218     222     440  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     184     194     378  
>=65 years     34     28     62  
Age  
[units: years]
Mean ± Standard Deviation
  48.53  ± 14.64     47.95  ± 14.52     48.24  ± 14.58  
Gender  
[units: participants]
     
Female     105     100     205  
Male     113     122     235  
Region of Enrollment  
[units: participants]
     
Italy     10     10     20  
Spain     7     6     13  
France     15     17     32  
Germany     92     91     183  
Poland     91     93     184  
United Kingdom     3     5     8  



  Outcome Measures
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1.  Primary:   Helicobacter Pylori Eradication Confirmed by Urea Breath Test   [ Time Frame: Week 6 and week 10 follow-up visits ]

Measure Type Primary
Measure Title Helicobacter Pylori Eradication Confirmed by Urea Breath Test
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No imputation method used, as this is the per protocol population, which excludes patients with missing values, or with protocol violations.

Reporting Groups
  Description
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)
Triple Therapy (OAC) 7 Days Ompeprazole 20 mg BID, Amoxicilin 500 mg 2 capsules BID and Clarithromycin 500 mg 1 tablet BID

Measured Values
    Quadruple Therapy (OBMT) 10 Days     Triple Therapy (OAC) 7 Days  
Number of Participants Analyzed  
[units: participants]
  178     161  
Helicobacter Pylori Eradication Confirmed by Urea Breath Test  
[units: Participants]
  166     112  

No statistical analysis provided for Helicobacter Pylori Eradication Confirmed by Urea Breath Test



2.  Secondary:   Number of Patients Experiencing Treatment Emergent Adverse Events.   [ Time Frame: at the end of treatment (day 8-14), week 6 and wek 10 follow-up visits. ]

Measure Type Secondary
Measure Title Number of Patients Experiencing Treatment Emergent Adverse Events.
Measure Description

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.  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population, described as all randomized patients having received at least one dose of study medication

Reporting Groups
  Description
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)
Triple Therapy (OAC) 7 Days Ompeprazole 20 mg BID, Amoxicilin 500 mg 2 capsules BID and Clarithromycin 500 mg 1 tablet BID

Measured Values
    Quadruple Therapy (OBMT) 10 Days     Triple Therapy (OAC) 7 Days  
Number of Participants Analyzed  
[units: participants]
  216     222  
Number of Patients Experiencing Treatment Emergent Adverse Events.  
[units: Participants]
  101     112  

No statistical analysis provided for Number of Patients Experiencing Treatment Emergent Adverse Events.



3.  Secondary:   H. Pylori Eradication and Presence or Past History of Peptic Ulcers   [ Time Frame: Week 6 and week 10 follow-up visits ]

Measure Type Secondary
Measure Title H. Pylori Eradication and Presence or Past History of Peptic Ulcers
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol population.

Reporting Groups
  Description
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)
Triple Therapy (OAC) 7 Days Ompeprazole 20 mg BID, Amoxicilin 500 mg 2 capsules BID and Clarithromycin 500 mg 1 tablet BID

Measured Values
    Quadruple Therapy (OBMT) 10 Days     Triple Therapy (OAC) 7 Days  
Number of Participants Analyzed  
[units: participants]
  19     18  
H. Pylori Eradication and Presence or Past History of Peptic Ulcers  
[units: Participants]
  18     15  

No statistical analysis provided for H. Pylori Eradication and Presence or Past History of Peptic Ulcers



4.  Secondary:   Clarithromycin Resistance   [ Time Frame: Measured at baseline ]

Measure Type Secondary
Measure Title Clarithromycin Resistance
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol analysis population

Reporting Groups
  Description
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)
Triple Therapy (OAC) 7 Days Ompeprazole 20 mg BID, Amoxicilin 500 mg 2 capsules BID and Clarithromycin 500 mg 1 tablet BID

Measured Values
    Quadruple Therapy (OBMT) 10 Days     Triple Therapy (OAC) 7 Days  
Number of Participants Analyzed  
[units: participants]
  33     25  
Clarithromycin Resistance  
[units: participants]
  30     2  

No statistical analysis provided for Clarithromycin Resistance



5.  Secondary:   Metronidazole Resistance   [ Time Frame: Measured at baseline ]

Measure Type Secondary
Measure Title Metronidazole Resistance
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per protocol population

Reporting Groups
  Description
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)
Triple Therapy (OAC) 7 Days Ompeprazole 20 mg BID, Amoxicilin 500 mg 2 capsules BID and Clarithromycin 500 mg 1 tablet BID

Measured Values
    Quadruple Therapy (OBMT) 10 Days     Triple Therapy (OAC) 7 Days  
Number of Participants Analyzed  
[units: participants]
  42     41  
Metronidazole Resistance  
[units: participants]
  38     28  

No statistical analysis provided for Metronidazole Resistance



6.  Secondary:   Overall Compliance to Study Medications   [ Time Frame: At the end of the treatment phase (days 8-14) ]

Measure Type Secondary
Measure Title Overall Compliance to Study Medications
Measure Description 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population.

Reporting Groups
  Description
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)
Triple Therapy (OAC) 7 Days Ompeprazole 20 mg BID, Amoxicilin 500 mg 2 capsules BID and Clarithromycin 500 mg 1 tablet BID

Measured Values
    Quadruple Therapy (OBMT) 10 Days     Triple Therapy (OAC) 7 Days  
Number of Participants Analyzed  
[units: participants]
  216     218  
Overall Compliance to Study Medications  
[units: participants]
Mean ± Standard Deviation
  97.58  ± 10.71     97.47  ± 14.91  

No statistical analysis provided for Overall Compliance to Study Medications



7.  Secondary:   Number of Patients With Bismuth Plasma Concentrations Above the Toxic Level   [ Time Frame: Baseline (both arms), end of treatment (Day 11-14) and end of study (Day 70) OBMT arm only ]

Measure Type Secondary
Measure Title Number of Patients With Bismuth Plasma Concentrations Above the Toxic Level
Measure Description 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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)
Triple Therapy (OAC) 7 Days Ompeprazole 20 mg BID, Amoxicilin 500 mg 2 capsules BID and Clarithromycin 500 mg 1 tablet BID

Measured Values
    Quadruple Therapy (OBMT) 10 Days     Triple Therapy (OAC) 7 Days  
Number of Participants Analyzed  
[units: participants]
  216     0  
Number of Patients With Bismuth Plasma Concentrations Above the Toxic Level  
[units: participants]
  0      

No statistical analysis provided for Number of Patients With Bismuth Plasma Concentrations Above the Toxic Level




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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