Compare Sequential and Quadruple Therapy for the Eradication of Helicobacter Pylori in Korea

• Sponsor: Seoul National University Bundang Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02159976
• Collaborator: SK Chemicals Co., Ltd. (Industry), Chong Kun Dang Pharmaceutical (Industry), HK inno.N Corporation (Industry), Green Cross Corporation (Industry)
• Enrollment: 390
• Location: 1
• Arms: 2
• Duration (Months): 21
• Patients Per Site Per Month: 18.5

Study Details

Study Description

Brief Summary

1. To compare 10-day sequential therapy and 14-day modified bismuth quadruple therapy and to establish more effective first-line regimen for the eradication of Helicobacter pylori in Korea.

2. To evaluate the effect of H. pylori eradication therapy on the symptom improvement of functional dyspepsia

Condition or Disease	Intervention/Treatment	Phase
Helicobacter Pylori Infection	Drug: Pantoprazole; Drug: Amoxicillin; Drug: Clarithromycin; Drug: Metronidazole; Drug: Tetracycline; Drug: Bismuth	N/A

Detailed Description

Emerging evidence shows that the eradication rate of proton pump inhibitor (PPI)-based triple therapy for the first-line treatment of Helicobacter pylori has decreased. The reason for the decrease in the efficacy of PPI-based triple therapy is mainly due to the increase in the resistance against clarithromycin. Sequential therapy seems to be more effective than the PPI-based triple therapy, however, the eradication rate of sequential therapy in Korea, which is mostly under 80%, is still not satisfactory. Modified bismuth quadruple therapy which replace metronidazole with amoxicillin (contained PPI, bismuth, tetracycline and amoxicillin) can be a promising regimen because the antibiotic resistance rate of tetracycline and amoxicillin are relatively low in Korea and amoxicillin is more easy to take in comparing with metronidazole. Therefore, the aim of this study is to compare 10-day sequential therapy and 14-day modified bismuth quadruple therapy and to establish more effective first-line regimen for the eradication of Helicobacter pylori in Korea.

In addition, previous studies reported that H. pylori infection also associated with functional dyspepsia (FD) and recommended H. pylori eradication in patients with FD. However, until now, there was no randomized prospective study in Korea, therefore the another aim of this study is to evaluate the effect of H. pylori eradication therapy on the symptom improvement of FD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 390 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multi-center, Randomized, Open-label, Parallel Design Clinical Trial to Compare 10-day Sequential Therapy and 14-day Modified Bismuth Quadruple Therapy for the Eradication of Helicobacter Pylori in Korea
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sequential therapy pantoprazole 40mg bid 10 days (D1-D10), amoxicillin 1000mg bid 5 days (D1-D5), clarithromycin 500mg bid 5 days (D6-D10), metronidazole 500mg tid 5 days (D6-D10)	Drug: Pantoprazole; Pantoprazole 40mg bid; Drug: Amoxicillin; Amoxicillin 1000mg bid; Drug: Clarithromycin; Clarithromycin 500mg bid; Drug: Metronidazole; Metronidazole 500mg tid
Experimental: Modified bismuth quadruple therapy pantoprazole 40mg bid 14 days (D1-D14) , amoxicillin 1000mg bid 14 days (D1-D14), tetracycline 1000mg bid 14 days (D1-D14), bismuth 600mg bid 14 days (D1-D14)	Drug: Pantoprazole; Pantoprazole 40mg bid; Drug: Amoxicillin; Amoxicillin 1000mg bid; Drug: Tetracycline; Tetracycline 1000mg bid; Drug: Bismuth; Bismuth 600mg bid

Outcome Measures

Primary Outcome Measures

1. Counts of Participants With Successful H. Pylori Eradication [4 weeks after termination of eradication therapy, up to 6 weeks]

Secondary Outcome Measures

1. Counts of Participants Whose Drug Compliance is More Than 85% [4 weeks after termination of eradication therapy, up to 6 weeks]

2. Counts of Participants With Adverse Event [4 weeks after termination of eradication therapy, up to 6 weeks]

3. Functional Dyspepsia Symptom Responses Rate [1 year after termination of eradication therapy]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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

• Patients who diagnosis of H. pylori infection by any of following three methods

• positive rapid urease test (CLOtest)

• histologic evidence of H. pylori by modified Giemsa staining

• positive 13C-urea breath test

Exclusion Criteria:

• Age under 18 years

• Previous eradication treatment for H. pylori

• Patients who took any drug which could influence the study results such as proton pump inhibitor, H2 blocker, mucosal protective agent and antibiotics

• History of gastrectomy

• 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

	Site	City	State	Country	Postal Code
1	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	463-707

Sponsors and Collaborators

• Seoul National University Bundang Hospital
• SK Chemicals Co., Ltd.
• Chong Kun Dang Pharmaceutical
• HK inno.N Corporation
• Green Cross Corporation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nayoung Kim, Professor, M.D, Ph.D., Seoul National University Bundang Hospital
• ClinicalTrials.gov Identifier: NCT02159976
• Other Study ID Numbers: B-1403/243-003
• First Posted: Jun 10, 2014
• Last Update Posted: May 13, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Nayoung Kim, Professor, M.D, Ph.D., Seoul National University Bundang Hospital: Helicobacter pylori
• Additional relevant MeSH terms: Amoxicillin; Metronidazole; Clarithromycin; Tetracycline; Pantoprazole; Bismuth

Study Results

Participant Flow

Arm/Group Title	Sequential Therapy	Modified Bismuth Quadruple Therapy
Arm/Group Description	pantoprazole 40mg bid 10 days (D1-D10), amoxicillin 1000mg bid 5 days (D1-D5), clarithromycin 500mg bid 5 days (D6-D10), metronidazole 500mg tid 5 days (D6-D10) Pantoprazole Amoxicillin Clarithromycin Metronidazole	pantoprazole 40mg bid 14 days (D1-D14) , amoxicillin 1000mg bid 14 days (D1-D14), tetracycline 1000mg bid 14 days (D1-D14), bismuth 600mg bid 14 days (D1-D14) Pantoprazole Amoxicillin Tetracycline Bismuth
Period Title: Overall Study
STARTED	195	195
COMPLETED	165	170
NOT COMPLETED	30	25

Baseline Characteristics

Arm/Group Title	Sequential Therapy	Modified Bismuth Quadruple Therapy	Total
Arm/Group Description	pantoprazole 40mg bid 10 days (D1-D10), amoxicillin 1000mg bid 5 days (D1-D5), clarithromycin 500mg bid 5 days (D6-D10), metronidazole 500mg tid 5 days (D6-D10) Pantoprazole Amoxicillin Clarithromycin Metronidazole	pantoprazole 40mg bid 14 days (D1-D14) , amoxicillin 1000mg bid 14 days (D1-D14), tetracycline 1000mg bid 14 days (D1-D14), bismuth 600mg bid 14 days (D1-D14) Pantoprazole Amoxicillin Tetracycline Bismuth	Total of all reporting groups
Overall Participants	195	195	390
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	154 79%	150 76.9%	304 77.9%
>=65 years	41 21%	45 23.1%	86 22.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.1 (12.6)	53.6 (13.2)	53.4 (12.9)
Sex: Female, Male (Count of Participants)
Female	92 47.2%	78 40%	170 43.6%
Male	103 52.8%	117 60%	220 56.4%
Region of Enrollment (participants) [Number]
Korea, Republic of	195 100%	195 100%	390 100%

Outcome Measures

1. Primary Outcome

Title	Counts of Participants With Successful H. Pylori Eradication
Time Frame	4 weeks after termination of eradication therapy, up to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sequential Therapy	Modified Bismuth Quadruple Therapy
Arm/Group Description	pantoprazole 40mg bid 10 days (D1-D10), amoxicillin 1000mg bid 5 days (D1-D5), clarithromycin 500mg bid 5 days (D6-D10), metronidazole 500mg tid 5 days (D6-D10) Pantoprazole Amoxicillin Clarithromycin Metronidazole	pantoprazole 40mg bid 14 days (D1-D14) , amoxicillin 1000mg bid 14 days (D1-D14), tetracycline 1000mg bid 14 days (D1-D14), bismuth 600mg bid 14 days (D1-D14) Pantoprazole Amoxicillin Tetracycline Bismuth
Measure Participants	195	195
Count of Participants [Participants]	146 74.9%	134 68.7%

2. Secondary Outcome

Title	Counts of Participants Whose Drug Compliance is More Than 85%
Time Frame	4 weeks after termination of eradication therapy, up to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sequential Therapy	Modified Bismuth Quadruple Therapy
Arm/Group Description	pantoprazole 40mg bid 10 days (D1-D10), amoxicillin 1000mg bid 5 days (D1-D5), clarithromycin 500mg bid 5 days (D6-D10), metronidazole 500mg tid 5 days (D6-D10) Pantoprazole Amoxicillin Clarithromycin Metronidazole	pantoprazole 40mg bid 14 days (D1-D14) , amoxicillin 1000mg bid 14 days (D1-D14), tetracycline 1000mg bid 14 days (D1-D14), bismuth 600mg bid 14 days (D1-D14) Pantoprazole Amoxicillin Tetracycline Bismuth
Measure Participants	176	177
Count of Participants [Participants]	165 84.6%	170 87.2%

3. Secondary Outcome

Title	Counts of Participants With Adverse Event
Time Frame	4 weeks after termination of eradication therapy, up to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sequential Therapy	Modified Bismuth Quadruple Therapy
Arm/Group Description	pantoprazole 40mg bid 10 days (D1-D10), amoxicillin 1000mg bid 5 days (D1-D5), clarithromycin 500mg bid 5 days (D6-D10), metronidazole 500mg tid 5 days (D6-D10) Pantoprazole Amoxicillin Clarithromycin Metronidazole	pantoprazole 40mg bid 14 days (D1-D14) , amoxicillin 1000mg bid 14 days (D1-D14), tetracycline 1000mg bid 14 days (D1-D14), bismuth 600mg bid 14 days (D1-D14) Pantoprazole Amoxicillin Tetracycline Bismuth
Measure Participants	195	195
Count of Participants [Participants]	93 47.7%	72 36.9%

4. Secondary Outcome

Title	Functional Dyspepsia Symptom Responses Rate
Time Frame	1 year after termination of eradication therapy

Outcome Measure Data

Analysis Population Description

SQT and PBAT were used for the initial treatment. Thereafter, treatment success and treatment failure group were divided. In the treatment failure group, secondary treatment was performed. Secondary endpoints were functional and dyspepsia symptom responses rate after successful treatment, not success in both treatment groups.

Arm/Group Title	In Eradication Success Group	In Eradication Failure Group
Arm/Group Description	functional dyspepsia symptom responses rate in eradication success group	functional dyspepsia symptom responses rate in eradication failure group
Measure Participants	60	3
complete (≥75%)	44 22.6%	0 0%
Satisfactory (50-74%)	1 0.5%	0 0%
Partial (25-49%)	6 3.1%	1 0.5%
Refractory (<25%)	9 4.6%	2 1%

Adverse Events

Arm/Group Title	Sequential Therapy		Modified Bismuth Quadruple Therapy
Arm/Group Description	pantoprazole 40mg bid 10 days (D1-D10), amoxicillin 1000mg bid 5 days (D1-D5), clarithromycin 500mg bid 5 days (D6-D10), metronidazole 500mg tid 5 days (D6-D10) Pantoprazole Amoxicillin Clarithromycin Metronidazole		pantoprazole 40mg bid 14 days (D1-D14) , amoxicillin 1000mg bid 14 days (D1-D14), tetracycline 1000mg bid 14 days (D1-D14), bismuth 600mg bid 14 days (D1-D14) Pantoprazole Amoxicillin Tetracycline Bismuth
All Cause Mortality
	Sequential Therapy		Modified Bismuth Quadruple Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sequential Therapy		Modified Bismuth Quadruple Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/195 (0%)		0/195 (0%)
Other (Not Including Serious) Adverse Events
	Sequential Therapy		Modified Bismuth Quadruple Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/195 (47.7%)		72/195 (36.9%)
Gastrointestinal disorders
Bloating	21/195 (10.8%)		11/195 (5.6%)
Epigastric soreness	15/195 (7.7%)		17/195 (8.7%)
Taste distortions	24/195 (12.3%)		4/195 (2.1%)
Nausea	14/195 (7.2%)		6/195 (3.1%)
Anorexia	2/195 (1%)		1/195 (0.5%)
Vomiting	0/195 (0%)		2/195 (1%)
Abdominal pain	4/195 (2.1%)		4/195 (2.1%)
Dyspepsia	4/195 (2.1%)		4/195 (2.1%)
Diarrhea	2/195 (1%)		12/195 (6.2%)
Constipation	2/195 (1%)		3/195 (1.5%)
Reflux	1/195 (0.5%)		1/195 (0.5%)
Stool color change	0/195 (0%)		3/195 (1.5%)
Nervous system disorders
Headache	1/195 (0.5%)		2/195 (1%)
Dizziness	1/195 (0.5%)		0/195 (0%)
Skin and subcutaneous tissue disorders
Rash and itching	2/195 (1%)		5/195 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.