The Efficacy of the Tailored Therapy Based on Antimicrobial Susceptibility for 2nd Eradication of H. Pylori

• Sponsor: Seoul National University Bundang Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02349685
• Collaborator: (none)
• Enrollment: 219
• Arms: 3
• Duration (Months): 53

Study Details

Study Description

Brief Summary

As increasing the antibiotics resistance, the effectiveness of traditional Helicobacter pylori (H. pylori) therapies has been declined coincidently. In this study, the investigators evaluated the efficacy of H. pylori eradication between a personalized therapy for H. pylori infection based on the results of antibiotics resistance by using H. pylori culture and minimal inhibitory concentration (MIC) and the traditional 2nd rescue regimens, and the investigators analyzed the prevalence of the antibiotic resistance after 1st eradication of

1. pylori in the tailored therapy group.

Condition or Disease	Intervention/Treatment	Phase
Helicobacter Infection	Procedure: H. pylori culture and antimicrobial susceptibility test; Drug: 14 day PBMT group; Drug: 14 day MEA group	N/A

Detailed Description

The patients who had shown the evidence of persistent H. pylori infection after the 1st eradication were enrolled for this study. After giving the informed consent about the method and efficacy (ITT and PP analysis) of the traditional 2nd rescue therapy and the tailored therapy for H. pylori infection based on culture and MIC, the patients were classified into the three regimen group under the patient's agreement and underwent 2nd eradication [14 days bismuth-based quadruple therapy (Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d.), 14 days moxifloxacin-containing triple therapy (PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d.), or tailored therapy based on H. pylori culture and MIC (select the 2nd rescue regimen between 14 days of bismuth-based quadruple therapy or 14 days moxifloxacin-containing triple therapy according to antibiotics susceptibility)].This study was analyzed the success of eradication for enrolled participants retrospectively, however the patients were enrolled prospectively based on previous study about antimicrobial susceptibility test for H. pylori in Korea.

Study Design

• Study Type: Interventional
• Actual Enrollment: 219 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Efficacy of the Culture Based Tailored Therapy for Helicobacter Pylori Eradication Comparing With the Traditional 2nd Line Rescue Therapy in Korean
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 14 day bismuth based quadruple therapy (PBMT) group Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d	Drug: 14 day PBMT group; Rescue therapy using 14 day PBMT regimen [Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d]
Experimental: 14 day Moxifloxacin containing triple therapy (MEA) group PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d.	Drug: 14 day MEA group; Rescue therapy using 14 day MEA regimen (PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d.)
Active Comparator: 14 day tailored therapy group based on H. pylori culture and antimicrobial sensitivity, select the 2nd rescue regimen between 14 days of bismuth-based quadruple therapy or 14 days moxifloxacin-containing triple therapy according to antibiotics susceptibility.	Procedure: H. pylori culture and antimicrobial susceptibility test; Antral and body biopsy specimens were evaluated separately. Organisms were identified as H. pylori by Gram staining, colony morphology, and positive oxidase, catalase, and urease reactions. Minimum inhibitory concentrations (MICs) were determined by the agar dilution method. Amoxicillin (Sigma Chemical Co., St. Louis, Mo.), clarithromycin (Abbott Laboratories, Abbott Park, Ill.), metronidazole (Sigma), tetracycline (Sigma) and moxifloxacin (Sigma) for the H. pylori isolates were examined by use of the serial twofold agar dilution method and the reference of susceptibility testing was according to the recommendations of the Clinical and Laboratory Standards Institute [amoxicillin (AMC), MIC ≥ 0.5 μg / ml; clarithromycin (CLA), MIC > 1.0 μ g / ml; metronidazole (MET), MIC > 8 μ g / ml; tetracycline (TC), MIC > 4 μ g / ml; and moxifloxacin (MOX), MIC > 1 μ g / ml).

Outcome Measures

Primary Outcome Measures

1. Number of Participants in Each Arm/Group With Successful H. Pylori Eradication [6 weeks after completion of eradication]

   the efficacy of H. pylori eradication between a personalized therapy for H. pylori infection based on the results of antibiotics resistance by using H. pylori culture and minimal inhibitory concentration (MIC) and the traditional 2nd rescue regimens. The eradication rate was evaluated by intention to treat (ITT)

Secondary Outcome Measures

1. Number of Participants in Each Arm/Group With Successful H. Pylori Eradication [6 weeks after completion of eradication]

   the efficacy of H. pylori eradication between a personalized therapy for H. pylori infection based on the results of antibiotics resistance by using H. pylori culture and minimal inhibitory concentration (MIC) and the traditional 2nd rescue regimens. The eradication rate was evaluated by per-protocol analysis (PP)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• The patients who proved a failure of 1st eradication of H. pylori with Proton pump inhibitor based triple therapy (PPI bid + amoxacillin 1g b.i.d + Clarithromycin 500 mg b.i.d) or sequential therapy (initial 5-day therapy with a combination of PPI b.i.d and amoxicillin 1g b.i.d, followed by 5 days of PPI b.i.d., clarithromycin 500mg b.i.d., and metronidazole 500mg t.i.d) following three methods

1. positive rapid urease test (CLOtest)

2. histologic evidence of H. pylori by modified Giemsa staining

3. positive 13C-Urea breath test

• Male and female Korean Adult (Aged ≥ 18 years)

Exclusion Criteria:

• Patients who received two or more eradication therapy for H. pylori infection

• 1. pylori eradication failure because of poor compliance

• the administration of antibiotics or the consumption of bismuth salts within 4 weeks or the administration of a proton pump inhibitor (PPI) within 2 weeks

• Advanced gastric cancer or other malignancy

• Abnormal liver function or liver cirrhosis

• Abnormal renal function or chronic kidney disease

• Other severe concurrent diseases

• Previous allergic reactions to the study drugs

• Pregnant or lactating women

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Seoul National University Bundang Hospital

Investigators

• Principal Investigator: Nayoung Kim, M.D., Ph. D, Seoul National University Bundang Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nayoung Kim, Professor, Seoul National University Bundang Hospital
• ClinicalTrials.gov Identifier: NCT02349685
• Other Study ID Numbers: B-1412/280-119
• First Posted: Jan 29, 2015
• Last Update Posted: Oct 4, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Nayoung Kim, Professor, Seoul National University Bundang Hospital: Helicobacter pylori; Personalized therapy; antimicrobial susceptibility; rescue therapy; culture
• Additional relevant MeSH terms: Helicobacter Infections; Anti-Infective Agents; Anti-Bacterial Agents

Study Results

Participant Flow

Arm/Group Title	14 Day PBMT Group	14 Day MEA Group	14 Day Tailored Therapy Group
Arm/Group Description	Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d 14 day PBMT group: Rescue therapy using 14 day PBMT regimen [Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d]	PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d. 14 day MEA group: Rescue therapy using 14 day MEA regimen (PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d.)	based on H. pylori culture and MIC, select the 2nd rescue regimen between 14 days of bismuth-based quadruple therapy or 14 days moxifloxacin-containing triple therapy according to antibiotics susceptibility.
Period Title: Overall Study
STARTED	89	89	41
COMPLETED	84	87	37
NOT COMPLETED	5	2	4

Baseline Characteristics

Arm/Group Title	14 Day PBMT Group	14 Day MEA Group	14 Day Tailored Therapy Group	Total
Arm/Group Description	Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d 14 day PBMT group: Rescue therapy using 14 day PBMT regimen [Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d]	PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d. 14 day MEA group: Rescue therapy using 14 day MEA regimen (PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d.)	based on H. pylori culture and MIC, select the 2nd rescue regimen between 14 days of bismuth-based quadruple therapy or 14 days moxifloxacin-containing triple therapy according to antibiotics susceptibility.	Total of all reporting groups
Overall Participants	89	89	41	219
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	49 55.1%	52 58.4%	27 65.9%	128 58.4%
>=65 years	40 44.9%	37 41.6%	14 34.1%	91 41.6%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	55.7	59.2	54.5	54.5
Sex: Female, Male (Count of Participants)
Female	43 48.3%	53 59.6%	25 61%	121 55.3%
Male	46 51.7%	36 40.4%	16 39%	98 44.7%
Region of Enrollment (participants) [Number]
Korea, Republic of	89 100%	89 100%	41 100%	219 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants in Each Arm/Group With Successful H. Pylori Eradication
Description	the efficacy of H. pylori eradication between a personalized therapy for H. pylori infection based on the results of antibiotics resistance by using H. pylori culture and minimal inhibitory concentration (MIC) and the traditional 2nd rescue regimens. The eradication rate was evaluated by intention to treat (ITT)
Time Frame	6 weeks after completion of eradication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	14 Day PBMT Group	14 Day MEA Group	14 Day Tailored Therapy Group
Arm/Group Description	Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d 14 day PBMT group: Rescue therapy using 14 day PBMT regimen [Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d]	PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d. 14 day MEA group: Rescue therapy using 14 day MEA regimen (PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d.)	based on H. pylori culture and MIC, select the 2nd rescue regimen between 14 days of bismuth-based quadruple therapy or 14 days moxifloxacin-containing triple therapy according to antibiotics susceptibility. H. pylori culture and antimicrobial susceptibility test: Antral and body biopsy specimens were evaluated separately. Organisms were identified as H. pylori by Gram staining, colony morphology, and positive oxidase, catalase, and urease reactions. Minimum inhibitory concentrations (MICs) were determined by the agar dilution method. Amoxicillin (Sigma Chemical Co., St. Louis, Mo.), clarithromycin (Abbott Laboratories, Abbott Park, Ill.), metronidazole (Sigma), tetracycline (Sigma) and moxifloxacin (Sigma) for the H. pylori isolates were examined by use of the serial twofold agar dilution method and the reference of susceptibility testing was according to the recommendations of the Clinical and Laboratory Standards Institute.
Measure Participants	89	89	41
Number [participants]	67 75.3%	63 70.8%	36 87.8%

2. Secondary Outcome

Title	Number of Participants in Each Arm/Group With Successful H. Pylori Eradication
Description	the efficacy of H. pylori eradication between a personalized therapy for H. pylori infection based on the results of antibiotics resistance by using H. pylori culture and minimal inhibitory concentration (MIC) and the traditional 2nd rescue regimens. The eradication rate was evaluated by per-protocol analysis (PP)
Time Frame	6 weeks after completion of eradication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	14 Day PBMT Group	14 Day MEA Group	14 Day Tailored Therapy Group
Arm/Group Description	Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d 14 day PBMT group: Rescue therapy using 14 day PBMT regimen [Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d]	PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d. 14 day MEA group: Rescue therapy using 14 day MEA regimen (PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d.)	based on H. pylori culture and MIC, select the 2nd rescue regimen between 14 days of bismuth-based quadruple therapy or 14 days moxifloxacin-containing triple therapy according to antibiotics susceptibility. H. pylori culture and antimicrobial susceptibility test: Antral and body biopsy specimens were evaluated separately. Organisms were identified as H. pylori by Gram staining, colony morphology, and positive oxidase, catalase, and urease reactions. Minimum inhibitory concentrations (MICs) were determined by the agar dilution method. Amoxicillin (Sigma Chemical Co., St. Louis, Mo.), clarithromycin (Abbott Laboratories, Abbott Park, Ill.), metronidazole (Sigma), tetracycline (Sigma) and moxifloxacin (Sigma) for the H. pylori isolates were examined by use of the serial twofold agar dilution method and the reference of susceptibility testing was according to the recommendations of the Clinical and Laboratory Standards Institute.
Measure Participants	84	87	37
Number [participants]	67 75.3%	63 70.8%	37 90.2%

Adverse Events

Arm/Group Title	14 Day PBMT Group		14 Day MEA Group		14 Day Tailored Therapy Group
Arm/Group Description	Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d 14 day PBMT group: Rescue therapy using 14 day PBMT regimen [Proton pump inhibitor (PPI) regular dose b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d. (three tablets at 30 min before meals and one tablet at 2 hours after dinner), metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d]		PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d. 14 day MEA group: Rescue therapy using 14 day MEA regimen (PPI regular dose b.i.d., moxifloxacin 400 mg q.d., and amoxicillin 1g b.i.d.)		based on H. pylori culture and MIC, select the 2nd rescue regimen between 14 days of bismuth-based quadruple therapy or 14 days moxifloxacin-containing triple therapy according to antibiotics susceptibility.
All Cause Mortality
	14 Day PBMT Group		14 Day MEA Group		14 Day Tailored Therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	14 Day PBMT Group		14 Day MEA Group		14 Day Tailored Therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		0/87 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	14 Day PBMT Group		14 Day MEA Group		14 Day Tailored Therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		0/87 (0%)		0/37 (0%)

Limitations/Caveats

Early termination leading to small number of subjects analyzed

More Information

Certain Agreements

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