High Dose Dual Therapy (HDDT) for Eradication of Helicobacter Pylori Infection

Bacterial Infection Due to Helicobacter Pylori (H. Pylori) Clinical Trial

— HDDT  

Official title:

High Dose Dual Therapy (HDDT) for Eradication of Helicobacter Pylori Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02553083
• Other study ID #: 0380-15-RMC
• Status: Recruiting
• Phase: Phase 4
• First received: July 26, 2015
• Last updated: January 29, 2018
• Start date: October 22, 2015
• Est. completion date: December 2021

Study information

• Verified date: January 2018
• Source: Rabin Medical Center
• Contact: Yaron Niv, MD
• Phone: 972504065401
• Email: yniv[@]clalit.org.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will performed a large-scale multi center trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naive (n = 300) patients with Hp infection. Consecutive symptomatic patients will be recruited in Israel and Spain when tested positive to Hp with serology and 13C urea breath test (13C-UBT) due to symptoms. Patients with gastric cancer, MALT lymphoma, and younger than 18 or older than 80 years old will be excluded. All patients will be naive to eradication therapy and will be randomized into one of three groups:

Group 1: Nexium 40 mg and amoxicillin 1.5 gr twice daily for 14 days Group 2: Nexium 40 mg and doxycycline 200 mg twice a day Group 3: Triple therapy of Nexium 20 mg, clarythromycin 500 mg, and amoxicillin 1gr twice a day for 10 days (regular accepted treatment).

All treatments will be stopped for a month and then 13CUBT will be repeated. The primary aim of the study is to assess eradication success, intentioned to treat and per protocol in the three treatment regimens.

The secondary aim of the study is to assess the safety of high dose amoxicillin and doxycycline.

Description:

Introduction High dose dual therapy (HDDT) for Helicobacter pylori (Hp) eradication was successfully tried in Taiwan for naive as well as experienced patients who failed a previous trial. This new approach relies on the rare resistance of Hp to amoxicillin which is about 1% all over the world. High intra gastric pH increases the efficacy of amoxicillin, thus the "old" dual therapy with a proton pump inhibitor and amoxicillin, but now in high doses for a longer time, has a potential to achieve a high eradication rate. Yang and co investigators randomized 450 naïve and 168 treatment-experienced patients in Taiwan, all infected by Hp, for HDDT, sequential and triple therapies. In the intention-to-treat analysis, Hp was eradicated in 95.3%, 85.3% and 80.7%, respectively in naïve, and 89.3%, 51.8% and 78.6%, respectively in experienced patients. No more adverse events were found in the HDDT group. They divided the high dose of amoxicillin into 4 doses a day. This approach may be unnecessary since Kim and colleagues demonstrated the same results when the same dose of amoxicillin was divided into 2 or 4 times a day. Recently doxcycylin was found effective in triple or quadruple therapy regimens with no adverse effect in the high dose of 200 mg BID.

The investigators will try that approach, successful in Asian patients, in a collaborative study that included Spanish and Israeli patients. The investigators will investigate whether a combination of a high-dose proton pump inhibitor and amoxicillin (dual therapy) will be more effective than standard first-line 10 days triple therapy in eradicating Hp. Since patients who are allergic to penicillin cannot be treated with amoxicillin The investigators will compare HDDT amoxicillin-based therapy also with HDDT doxycycline -based therapy.

Protocol

The investigators will performed a large-scale multi center trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naive (n = 300) patients with Hp infection. Consecutive symptomatic patients will be recruited in Israel and Spain when tested positive to Hp with serology and 13CUBT due to symptoms. Patients with gastric cancer, MALT lymphoma, and younger than 18 or older than 80 years old will be excluded. All patients will be naive to eradication therapy and will be randomized into one of three groups:

Group 1: Nexium 40 mg and amoxicillin 1.5 gr twice daily for 14 days Group 2: Nexium 40 mg and doxycycline 200 mg twice a day Group 3: Triple therapy of Nexium 20 mg, clarythromycin 500 mg, and amoxicillin 1gr twice a day for 10 days (regular accepted treatment).

All treatments will be stopped for a month and then 13CUBT will be repeated. The primary aim of the study is to assess eradication success, intentioned to treat and per protocol in the three treatment regimens.

The secondary aim of the study is to assess the safety of high dose amoxicillin and doxycycline .

Hypothesis The investigators hypothesize that the success rate of eradication therapy in groups 1 and 2 will be significantly better than of group 3, with a good safety profile. If so, HDDT will be the answer for Hp eradication in areas with high Clarithromycin and metronidazole resistance.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2021
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients infected with Helicobacter pylori

Exclusion Criteria:

• Patients with gastric cancer or MALT lymphoma

Related Conditions & MeSH terms

• Bacterial Infection Due to Helicobacter Pylori (H. Pylori)
• Bacterial Infections
• Communicable Diseases
• Helicobacter Infections
• Infection

Intervention

Drug:
• Nexium 40 mg
Nexium 40 mg twice daily for 14 days
• amoxicillin 1.5 gr
amoxicillin 1.5 gr twice daily for 14 days
• doxycycline 200 mg
doxycycline 200 mg twice daily for 14 days
• Nexium 20 mg
Nexium 20 mg twice a day for 10 days
• clarythromicin 500 mg
clarythromicin 500 mg twice a day for 10 days
• amoxicillin 1gr
amoxicillin 1gr twice a day for 10 days

Locations

Country	Name	City	State
Israel	Rabin Medical Center	Petach Tikva

Sponsors (1)

Lead Sponsor	Collaborator
Rabin Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Eradication rate	Eradication rate	2 weeks therapy