Levofloxacin-containing Therapies In Second Line Helicobacter Pylori Eradication

• Sponsor: Chang Gung Memorial Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02596620
• Collaborator: (none)
• Enrollment: 164
• Arms: 2
• Duration (Months): 25

Study Details

Study Description

Brief Summary

Asia Pacific Consensus states that levofloxacin-based triple therapy as an alternative second-line therapy after Helicobacter pylori (H. pylori) eradication failure when bismuth salts are not available. The investigators compare the efficacies of 10-day levofloxacin-based sequential therapy and 10-day triple therapy in the treatment for patients after failure of standard triple therapy and to determine what clinical and bacterial factors influencing the efficacy of salvage regimens.

Condition or Disease	Intervention/Treatment	Phase
Helicobacter Pylori Infection	Drug: Nexium; Drug: Amolin; Drug: Cravit; Drug: Flagyl	N/A

Detailed Description

In this randomized-controlled trial , the investigator recruited participants with H pylori infection after failure of first line standard triple therapy. Using a computer-generated randomization sequence, the investigators randomly allocated patients to either 10-day levofloxacin-containing sequential (EALM, esomeprazole 40 mg b.d., amoxicillin 1 g b.d.for 5 days and followed by esomeprazole 40 mg b.d., levofloxacin 500 mg qd and metronidazole for 5 days) or 10-day levofloxacin-containing triple therapy (EAL, esomeprazole 40 mg b.d., amoxicillin 1 g b.d., and levofloxacin 500 mg qd) at a 1:1 ratio. The primary outcome was the eradication rate by intention-to-treat and per-protocol analyses.

Study Design

• Study Type: Interventional
• Actual Enrollment: 164 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: The Efficacy of 10-day Metronidazole and Levofloxacin Containing Sequential Therapy and 10-day Levofloxacin-containing Triple Therapy In Second Line Helicobacter Pylori Eradication Therapies
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequential therapy Esomeprazole (Nexium)(40 mg) 1 tablet twice daily, amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 5 days followed by esomeprazole (Nexium) (40 mg) twice daily, levofloxacin(Cravit)(500 mg), 1 tablet once daily and metronidazole (Flagyl)(250 mg) 2 tablets three times daily for 5 days	Drug: Nexium; Esomeprazole (Nexium)(40 mg) 1 tablet twice daily for 10 days in both arms; Other Names: Esomeprazole ; Drug: Amolin; Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for the first 5 days in the Sequential arm; Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 10 days for triple therapy arm; Other Names: Amoxicillin ; Drug: Cravit; Levofloxacin(Cravit)(500 mg) 1 tablet once dialy for the last 5 days in the sequential arm and 1 tablets once daily for 10 days in the triple therapy arm; Other Names: Levofloxacin ; Drug: Flagyl; Metronidazole (Flagyl)(250 mg) 2 # tid for the last 5 days in the sequential arm; Other Names: Metronidazole
Active Comparator: Triple therapy Esomeprazole (Nexium)(40 mg) 1 tablet twice daily; amoxicillin (Amolin)(500 mg) 2 tablets twice daily and levofloxacin(Cravit)(500 mg), 1 tablet once daily for 10 days	Drug: Nexium; Esomeprazole (Nexium)(40 mg) 1 tablet twice daily for 10 days in both arms; Other Names: Esomeprazole ; Drug: Amolin; Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for the first 5 days in the Sequential arm; Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 10 days for triple therapy arm; Other Names: Amoxicillin ; Drug: Cravit; Levofloxacin(Cravit)(500 mg) 1 tablet once dialy for the last 5 days in the sequential arm and 1 tablets once daily for 10 days in the triple therapy arm; Other Names: Levofloxacin

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Successful Eradication of H. Pylori [Negative results of H.pylori 4 weeks after eradication]

   Successful eradication of H. pylori is defined as (1) negative results of both rapid urease test and histology, or (2) a negative result of urea breath test at 4 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Consecutive H. pylori-infected participants, at least 18 years of age, with endoscopically proven peptic ulcer diseases or gastritis who failed first-line eradication therapies with standard triple regimens (PPI twice daily, 500 mg of clarithromycin twice daily and 1 g of amoxicillin twice daily)

Exclusion Criteria:

• Ingestion of antibiotics, bismuth, or proton-pump inhibitors within the prior 4 weeks

• Use of non-steroidal anti-inflammatory drugs within the prior 4 weeks

• Participants with allergic history to the medications used

• Participants with previous gastric surgery

• The coexistence of serious concomitant illness (for example, decompensated liver cirrhosis, uremia)

• Pregnant women.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Chang Gung Memorial Hospital

Investigators

• Principal Investigator: Wei-Chen Tai, M.D., Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Taiwan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wei-Chen Tai M.D., Assistant Professor, Chang Gung Memorial Hospital
• ClinicalTrials.gov Identifier: NCT02596620
• Other Study ID Numbers: CMRPG8C0201
• First Posted: Nov 4, 2015
• Last Update Posted: Feb 28, 2017
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Wei-Chen Tai M.D., Assistant Professor, Chang Gung Memorial Hospital: Helicobacter pylori; Proton pump inhibitor; Eradication
• Additional relevant MeSH terms: Amoxicillin; Metronidazole; Levofloxacin; Esomeprazole

Study Results

Participant Flow

Recruitment Details	164 patients who had failed the H pylori eradication attempts using the standard triple therapy (proton pump inhibitor bid, clarithromycin 500 mg bid, amoxicillin 1 g bid × 7 days) were randomly assigned to either an sequential therapy group (EALM)(n = 82) or a 10-day levofloxacin-containing teriple therapy group (EAL)(n = 82).
Pre-assignment Detail	We excluded those patients who had taken antibiotics, bismuth, proton-pump inhibitors, or non-steroidal anti-inflammatory drugs within the previous 4 weeks, were allergic to the medications used, had a history of previous gastric surgery or serious concomitant illness, or were currently pregnant.

Arm/Group Title	Sequential Therapy	Triple Therapy
Arm/Group Description	esomeprazole 40 mg bid and amoxicillin 1 g bid for 5 days, followed by esomeprazole 40 mg bid, levofloxacin 500 mg qd, and metronidazole 500 mg tid, for 5 days	levofloxacin 500 mg qd, amoxicillin 1 g bid, and esomeprazole 40 mg bid
Period Title: Overall Study
STARTED	82	82
COMPLETED	81	81
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Sequential Therapy	Triple Therapy	Total
Arm/Group Description	Esomeprazole (Nexium)(40 mg) 1 tablet twice daily, amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 5 days followed by esomeprazole (Nexium) (40 mg) twice daily, levofloxacin(Cravit)(500 mg), 1 tablet once daily and metronidazole (Flagyl)(250 mg) 2 tablets three times daily for 5 days Nexium: Esomeprazole (Nexium)(40 mg) 1 tablet twice daily for 10 days in both arms Amolin: Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for the first 5 days in the Sequential arm; Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 10 days for triple therapy arm Cravit: Levofloxacin(Cravit)(500 mg) 1 tablet once dialy for the last 5 days in the sequential arm and 1 tablets once daily for 10 days in the triple therapy arm Flagyl: Metronidazole (Flagyl)(250 mg) 2 # tid for the last 5 days in the sequential arm	Esomeprazole (Nexium)(40 mg) 1 tablet twice daily; amoxicillin (Amolin)(500 mg) 2 tablets twice daily and levofloxacin(Cravit)(500 mg), 1 tablet once daily for 10 days Nexium: Esomeprazole (Nexium)(40 mg) 1 tablet twice daily for 10 days in both arms Amolin: Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for the first 5 days in the Sequential arm; Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 10 days for triple therapy arm Cravit: Levofloxacin(Cravit)(500 mg) 1 tablet once dialy for the last 5 days in the sequential arm and 1 tablets once daily for 10 days in the triple therapy arm	Total of all reporting groups
Overall Participants	82	82	164
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	70 85.4%	68 82.9%	138 84.1%
>=65 years	12 14.6%	14 17.1%	26 15.9%
Gender (Count of Participants)
Female	46 56.1%	42 51.2%	88 53.7%
Male	36 43.9%	40 48.8%	76 46.3%
Region of Enrollment (participants) [Number]
Taiwan	82 100%	82 100%	164 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Successful Eradication of H. Pylori
Description	Successful eradication of H. pylori is defined as (1) negative results of both rapid urease test and histology, or (2) a negative result of urea breath test at 4 weeks.
Time Frame	Negative results of H.pylori 4 weeks after eradication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sequential Therapy	Triple Therapy
Arm/Group Description	Esomeprazole (Nexium)(40 mg) 1 tablet twice daily, amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 5 days followed by esomeprazole (Nexium) (40 mg) twice daily, levofloxacin(Cravit)(500 mg), 1 tablet once daily and metronidazole (Flagyl)(250 mg) 2 tablets three times daily for 5 days Nexium: Esomeprazole (Nexium)(40 mg) 1 tablet twice daily for 10 days in both arms Amolin: Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for the first 5 days in the Sequential arm; Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 10 days for triple therapy arm Cravit: Levofloxacin(Cravit)(500 mg) 1 tablet once dialy for the last 5 days in the sequential arm and 1 tablets once daily for 10 days in the triple therapy arm Flagyl: Metronidazole (Flagyl)(250 mg) 2 # tid for the last 5 days in the sequential arm	Esomeprazole (Nexium)(40 mg) 1 tablet twice daily; amoxicillin (Amolin)(500 mg) 2 tablets twice daily and levofloxacin(Cravit)(500 mg), 1 tablet once daily for 10 days Nexium: Esomeprazole (Nexium)(40 mg) 1 tablet twice daily for 10 days in both arms Amolin: Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for the first 5 days in the Sequential arm; Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 10 days for triple therapy arm Cravit: Levofloxacin(Cravit)(500 mg) 1 tablet once dialy for the last 5 days in the sequential arm and 1 tablets once daily for 10 days in the triple therapy arm
Measure Participants	81	81
Number (95% Confidence Interval) [percentage of eradication]	91.4	81.5

Adverse Events

Time Frame	2 years
Arm/Group Title	Sequential Therapy		Triple Therapy
Arm/Group Description	Esomeprazole (Nexium)(40 mg) 1 tablet twice daily, amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 5 days followed by esomeprazole (Nexium) (40 mg) twice daily, levofloxacin(Cravit)(500 mg), 1 tablet once daily and metronidazole (Flagyl)(250 mg) 2 tablets three times daily for 5 days Nexium: Esomeprazole (Nexium)(40 mg) 1 tablet twice daily for 10 days in both arms Amolin: Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for the first 5 days in the Sequential arm; Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 10 days for triple therapy arm Cravit: Levofloxacin(Cravit)(500 mg) 1 tablet once dialy for the last 5 days in the sequential arm and 1 tablets once daily for 10 days in the triple therapy arm Flagyl: Metronidazole (Flagyl)(250 mg) 2 # tid for the last 5 days in the sequential arm		Esomeprazole (Nexium)(40 mg) 1 tablet twice daily; amoxicillin (Amolin)(500 mg) 2 tablets twice daily and levofloxacin(Cravit)(500 mg), 1 tablet once daily for 10 days Nexium: Esomeprazole (Nexium)(40 mg) 1 tablet twice daily for 10 days in both arms Amolin: Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for the first 5 days in the Sequential arm; Amoxicillin (Amolin)(500 mg) 2 tablets twice daily for 10 days for triple therapy arm Cravit: Levofloxacin(Cravit)(500 mg) 1 tablet once dialy for the last 5 days in the sequential arm and 1 tablets once daily for 10 days in the triple therapy arm
All Cause Mortality
	Sequential Therapy		Triple Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sequential Therapy		Triple Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/81 (0%)		0/81 (0%)
Other (Not Including Serious) Adverse Events
	Sequential Therapy		Triple Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/81 (23.5%)		9/81 (11.1%)
Gastrointestinal disorders
Abdominal pain	5/81 (6.2%)	5	2/81 (2.5%)	2
Diarrhea	2/81 (2.5%)	2	1/81 (1.2%)	1
Nausea/vomiting	7/81 (8.6%)	7	4/81 (4.9%)	4
General disorders
Dizziness	4/81 (4.9%)	4	1/81 (1.2%)	1
Headache	3/81 (3.7%)	3	1/81 (1.2%)	1
Other	2/81 (2.5%)	2	1/81 (1.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.