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

History of Changes

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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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

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Restrictions vary in accordance with the agreement with investigators. Axcan will allow publication after a multi-centre publication or after an agreed period, subject to review by Axcan for confidentiality and intellectual protection.

Limitations and Caveats

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
No text entered.

Results Point of Contact:

Name/Title: Monique Giguere, PhD, Programs Director,
Organization: Axcan Pharma Inc.
phone: 1-800-565-3255 ext 2078

No publications provided by Axcan Pharma

Publications automatically indexed to this study:

Malfertheiner P, Bazzoli F, Delchier JC, Celiñski K, Giguère M, Rivière M, Mégraud F; Pylera Study Group. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet. 2011 Mar 12;377(9769):905-13. Epub 2011 Feb 21.

Responsible Party:	Dr. Monique Giguere, Axcan Pharma inc.
ClinicalTrials.gov Identifier:	NCT00669955 History of Changes
Other Study ID Numbers:	PYLHp07-01
Study First Received:	April 29, 2008
Results First Received:	June 21, 2010
Last Updated:	August 3, 2010
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices United Kingdom: National Health Service Spain: Ethics Committee Spain: Ministry of Health Poland: Ministry of Health Ireland: Irish Medicines Board Italy: National Bioethics Committee France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Netherlands: Medicines Evaluation Board (MEB)

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