High Dose Dual Therapy (HDDT) for Eradication of Helicobacter Pylori Infection
High Dose Dual Therapy (HDDT) for Eradication of Helicobacter Pylori Infection
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.
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.
Inclusion Criteria:

 -  Patients infected with Helicobacter pylori

 Exclusion Criteria:

 -  Patients with gastric cancer or MALT lymphoma