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

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.

Study Overview

• Status: Unknown
• Conditions: Bacterial Infection Due to Helicobacter Pylori (H. Pylori)
• Intervention / Treatment: Drug: Nexium 40 mg; Drug: amoxicillin 1.5 gr; Drug: doxycycline 200 mg; Drug: Nexium 20 mg; Drug: clarythromicin 500 mg; Drug: amoxicillin 1gr

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yaron Niv, MD; Phone Number: 972504065401; Email: yniv@clalit.org.il

Study Locations

• Israel
  • Petach Tikva, Israel, 49100
    • Recruiting
    • Rabin Medical Center
    • Contact: Yaron Niv, MD; Phone Number: 97239377237; Email: yniv@clalit.org.il
    • Principal Investigator: Yaron Niv, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients infected with Helicobacter pylori

Exclusion Criteria:

• Patients with gastric cancer or MALT lymphoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group 1; Nexium 40 mg and amoxicillin 1.5 gr twice daily for 14 days	Drug: Nexium 40 mg; Nexium 40 mg twice daily for 14 days; Drug: amoxicillin 1.5 gr; amoxicillin 1.5 gr twice daily for 14 days
ACTIVE_COMPARATOR: Group 2; Nexium 40 mg and doxycycline 200 mg twice daily for 14 days	Drug: Nexium 40 mg; Nexium 40 mg twice daily for 14 days; Drug: doxycycline 200 mg; doxycycline 200 mg twice daily for 14 days
ACTIVE_COMPARATOR: Group 3; Nexium 20 mg, clarythromicin 500 mg, and amoxicillin 1 gr twice daily for 14 days	Drug: Nexium 20 mg; Nexium 20 mg twice a day for 10 days; Drug: clarythromicin 500 mg; clarythromicin 500 mg twice a day for 10 days; Drug: amoxicillin 1gr; amoxicillin 1gr twice a day for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate	Eradication rate	2 weeks therapy

Collaborators and Investigators

• Sponsor: Rabin Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 22, 2015
• Primary Completion (ANTICIPATED): September 1, 2020
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: July 26, 2015
• First Submitted That Met QC Criteria: September 16, 2015
• First Posted (ESTIMATE): September 17, 2015

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2018
• Last Update Submitted That Met QC Criteria: January 29, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Bacterial Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antimalarials; Doxycycline; Amoxicillin; Esomeprazole
• Other Study ID Numbers: 0380-15-RMC