Efficacy of Seven-day Combined Rabeprazole Plus Levofloxacin Plus Augmentin for Eradication of Helicobacter Pylori

• ClinicalTrials.gov Identifier: NCT01575899
• Recruitment Status: Terminated
• First Posted: April 12, 2012
• Results First Posted: August 31, 2012
• Last Update Posted: August 31, 2012
• Sponsor: Buddhist Tzu Chi General Hospital
• Information provided by (Responsible Party): Ming-Cheh Chen, Buddhist Tzu Chi General Hospital

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Helicobacter Pylori Infection
• Interventions: Drug: Levofloxacin-Amox/clav.; Drug: Clarithromycin-Amoxicillin
• Enrollment: 208

Participant Flow

Recruitment Details	We included H. pylori-positive adult patients assessed by the rapid urease test and histology during the period December 2007 to December 2009 from the out-patient clinic of a single medical center located at Hualien, Eastern Taiwan.
Pre-assignment Details	We excluded patients under the age of 20, woman in pregnancy or breast feeding, those with concomitant illness or conditions (i.e., cardiopulmonary, hepatic, renal diseases, neoplastic diseases), those with severe complication of peptic ulcer disease, like obstruction or perforation, those with allergy to any of the drugs used.

Arm/Group Title	Levofloxacin-Amox/Clav.	Clarithromycin-Amoxicillin	Levofloxacin-Amox/Clav. (Re-eradication)
Arm/Group Description	7-day levofloxacin, amoxicillin/clavulanate, rabeprazole for Hp eradication.	7-day clarithromycin, amoxicillin, rabeprazole for Hp eradication.	7-day levofloxacin, amoxicillin/clavulanate and rabeprazole for re-eradication of patient still with evidence of Hp infection after previous intent of eradication.
Period Title: Overall Study
Started	73	73	62 [1]
Completed	68	68	60
Not Completed	5	5	2
Reason Not Completed
Lost to Follow-up	3	4	2
Protocol Violation	2	1	0
[1] Included patients still with Hp infection after previous therapy without levofloxacin and Augmentin.

Baseline Characteristics

Arm/Group Title		Levofloxacin-Amox/Clav.	Clarithromycin-Amoxicillin	Levofloxacin-Amox/Clav. (Re-eradication)	Total
Arm/Group Description		7-day levofloxacin, amoxicillin/clavulanate, rabeprazole for Hp eradication.	7-day clarithromycin, amoxicillin, rabeprazole for Hp eradication.	7-day levofloxacin, amoxicillin/clavulanate and rabeprazole for re-eradication of patient still with evidence of Hp infection after previous intent of eradication.	Total of all reporting groups
Overall Number of Baseline Participants		73	73	62	208
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	73 participants	73 participants	62 participants	208 participants
		52.82 (12.08)	54.63 (14.42)	54.68 (11.81)	54.01 (12.77)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	73 participants	73 participants	62 participants	208 participants
< 54 years		38	34	25	97
>=54 years		35	39	37	111
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	73 participants	73 participants	62 participants	208 participants
	Female	35 47.9%	40 54.8%	38 61.3%	113 54.3%
	Male	38 52.1%	33 45.2%	24 38.7%	95 45.7%
Resident area [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	73 participants	73 participants	62 participants	208 participants
Urban area		30	24	19	73
Rural area		43	49	43	135
		[1] Measure Description: Comparison about resident area of participants, living in urban area or rural area.
Endoscopic finding [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	73 participants	73 participants	62 participants	208 participants
With peptic ulcer		30	35	21	86
Without peptic ulcer		43	38	41	122
		[1] Measure Description: Comparison between participant's endoscopic finding with or without peptic ulcer disease.
Follow up method [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	73 participants	73 participants	62 participants	208 participants
C13-UBT		65	65	55	185
CLO test		5	4	5	14
No follow up		3	4	2	9
		[1] Measure Description: Information about the follow up method to confirmed the post-treatment Hp status of participants.

Outcome Measures

1. Primary Outcome

Title	Eradication Rate (Participants Naive to Anti-H. Pylori Treatment)
Description	A negative post-treatment 13C-urea breath test or CLO test result at more than 4 weeks after complete use of drug for treatment.
Time Frame	4 weeks after complete use of drug for treatment

Outcome Measure Data

Analysis Population Description

Intent to treat analysis of eradication (negative result of follow up method) measured 4 weeks after complete the treatment, for participants never received anti-H. pylori treatment before.

Arm/Group Title	Levofloxacin-Amox/Clav.	Clarithromycin-Amoxicillin
Arm/Group Description:	7-day levofloxacin, amoxicillin/clavulanate, rabeprazole for Hp eradication.	7-day clarithromycin, amoxicillin, rabeprazole for Hp eradication.
Overall Number of Participants Analyzed	73	73
Measure Type: Number; Unit of Measure: percentage of eradicated participants
	78.1	57.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levofloxacin-Amox/Clav., Clarithromycin-Amoxicillin
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.008
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.629
	Confidence Interval	(2-Sided) 95%; 1.28 to 5.42
	Parameter Dispersion	Type: Standard Error of the mean; Value: 3.1526
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Eradication Rate of Participants Living in Rural Area.
Description	Subgroup analysis on eradication rate (percentage of participants with a negative result of C13 or CLO test at least four weeks after treatment) according to resident area of participants, especially who are living in rural area.
Time Frame	4 weeks after complete use of drug for treatment

Outcome Measure Data

Analysis Population Description

Subgroup analysis (intent-to-treat) on eradication rate of participants who are living in rural area of Taiwan.

Arm/Group Title	Levofloxacin-Amox/Clav.	Clarithromycin-Amoxicillin
Arm/Group Description:	Participants who are living in rural area and received 7-day levofloxacin, amoxicillin/clavulanate and rabeprazole for Hp eradication.	Participants who are living in rural area and received 7-day clarithromycin, amoxicillin and rabeprazole for Hp eradication.
Overall Number of Participants Analyzed	43	49
Measure Type: Number; Unit of Measure: percentage of eradicated participants
	81.4	51.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levofloxacin-Amox/Clav., Clarithromycin-Amoxicillin
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.87
	Confidence Interval	(2-Sided) 95%; 1.5 to 10.02
	Parameter Dispersion	Type: Standard Error of the mean; Value: 3.2589
	Estimation Comments	[Not Specified]

3. Other Pre-specified Outcome

Title	Re-eradication Rate
Description	Re-eradication successful rate (percentage of participants with a negative result of C13 or CLO test at least four weeks after the 2nd treatment) with 7-day levofloxacin, amoxicillin/clavulanate and rabeprazole for patients still with Hp infection previously treated with regimen without levofloxacin and Augmentin.
Time Frame	4 weeks after complete use of drug for treatment

Outcome Measure Data

Analysis Population Description

This intent-to treat analysis is without control group, including patients still with Hp infection previously treated with regimen without levofloxacin and Augmentin.

Arm/Group Title	Levofloxacin-Amox/Clav. (Re-eradication)
Arm/Group Description:	7-day levofloxacin, amoxicillin/clavulanate and rabeprazole for patients still with Hp infection previously treated with regimen without levofloxacin and Augmentin.
Overall Number of Participants Analyzed	62
Measure Type: Number; Unit of Measure: percentage of successful re-eradication
	72.6

Adverse Events

Time Frame	Since participants enrolled into the study till completed the follow up, at least five weeks.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Levofloxacin-Amox/Clav.		Clarithromycin-Amoxicillin		Levofloxacin-Amox/Clav. (Re-eradication)
Arm/Group Description	7-day levofloxacin, amoxicillin/clavulanate, rabeprazole for Hp eradication.		7-day clarithromycin, amoxicillin, rabeprazole for Hp eradication.		7-day levofloxacin, amoxicillin/clavulanate and rabeprazole for re-eradication of patient still with evidence of Hp infection after previous intent of eradication.
All-Cause Mortality
	Levofloxacin-Amox/Clav.		Clarithromycin-Amoxicillin		Levofloxacin-Amox/Clav. (Re-eradication)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Levofloxacin-Amox/Clav.		Clarithromycin-Amoxicillin		Levofloxacin-Amox/Clav. (Re-eradication)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/73 (1.37%)		0/73 (0.00%)		0/62 (0.00%)
Gastrointestinal disorders
Visited our emergency room * [1]	1/10 (10.00%)	1	0/11 (0.00%)	0	0/17 (0.00%)	0
* Indicates events were collected by non-systematic assessment; [1] Vomiting during eradication, visited our ER, improved after symptomatic treatment, then the case was loss in follow up.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	Levofloxacin-Amox/Clav.		Clarithromycin-Amoxicillin		Levofloxacin-Amox/Clav. (Re-eradication)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/73 (13.70%)		11/73 (15.07%)		17/62 (27.42%)
Gastrointestinal disorders
Nausea / Hiccough * [1]	4/73 (5.48%)	4	4/73 (5.48%)	4	4/62 (6.45%)	4
Loose stool / Diarrhea * [2]	3/73 (4.11%)	3	1/73 (1.37%)	1	8/62 (12.90%)	8
Change in appetite / Bitter sensation * [3]	2/73 (2.74%)	2	4/73 (5.48%)	4	0/62 (0.00%)	0
Abdominal fullness / Flatus * [4]	1/73 (1.37%)	1	3/73 (4.11%)	3	4/62 (6.45%)	4
General disorders
Insomnia * [5]	1/73 (1.37%)	1	0/73 (0.00%)	0	4/62 (6.45%)	4
* Indicates events were collected by non-systematic assessment; [1] Hiccough and/or sensation of nausea; [2] Diarrhea or loose stool passage.; [3] Bitter sensation in tongue, change in taste or appetite.; [4] Flatus, abdominal fullness and gas passage.; [5] Poor sleep.

Limitations and Caveats

The limitation of this study is the local primary resistance of Hp to levofloxacin and to amoxicillin/clavulanate is unknown. We are currently engaged in an on-going investigation of the influence of CYP2C19 genotypes on this new regimen.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Ming-Cheh, Chen
• Organization: Buddhist Tzu Chi General Hospital
• Phone: +886-910-521003
• EMail: MingCheh_chen@tzuchi.com.tw

• Responsible Party: Ming-Cheh Chen, Buddhist Tzu Chi General Hospital
• ClinicalTrials.gov Identifier: NCT01575899
• Other Study ID Numbers: IRB096-28
• First Submitted: April 10, 2012
• First Posted: April 12, 2012
• Results First Submitted: April 19, 2012
• Results First Posted: August 31, 2012
• Last Update Posted: August 31, 2012