<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02249546</url>
  </required_header>
  <id_info>
    <org_study_id>201406074MINC</org_study_id>
    <nct_id>NCT02249546</nct_id>
  </id_info>
  <brief_title>Efficacy of Acetylcysteine-containing Triple Therapy in the First Line of Helicobacter Pylori Infection</brief_title>
  <official_title>Comparison of the Efficacy of Triple Therapy With or Without Acetylcysteine in the First Line of Helicobacter Pylori Infection- A Multicenter Randomized Comparative Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Helicobacter pylori infection has been shown to be associated with the development of gastric&#xD;
      cancer and peptic ulcer diseases. Eradication of H. pylori infection could reduce the&#xD;
      occurence or recurrence of these diseases. The triple treatment including a proton pump&#xD;
      inhibitor, clarithromycin, and amoxicillin or metronidazole to treat H pylori infection,&#xD;
      proposed at the first Maastricht conference has become universal since all the consensus&#xD;
      conferences and guidelines around the world recommended it. However, the eradication rate of&#xD;
      clarithromycin-based triple therapy has been declining in recent years, probably related to&#xD;
      the increasing resistant rate to clarithromycin. It was estimated that 15-20% of patients&#xD;
      would fail from first line standard eradication therapy and need second line rescue therapy.&#xD;
&#xD;
      The H. pylori persistence in human infections and its resistance to the drugs commonly used&#xD;
      in antimicrobial therapy have been attributed not only to genetic variability, but also to&#xD;
      ability of H. pylori to form biofilm as a strategy to overcome environmental stress and to&#xD;
      protect itself. Several recent reports indicate that H. pylori forms biofilm either in vitro&#xD;
      or in vivo, N-acetylcysteine (NAC) were thought to reduce and prevent biofilm formation. Two&#xD;
      small-scale clinical trials showed NAC offers additive effect on eradication effects of H.&#xD;
      pylori therapy. A recent trial showed N-acetylcysteine pre-treatment before a culture-guided&#xD;
      antibiotic regimen is effective in treating refractory H. pylori infection.&#xD;
&#xD;
      Aims: Therefore, we aim to assess&#xD;
&#xD;
        1. Whether triple therapy containing N-acetyl cysteine is more effective than standard&#xD;
           triple therapy&#xD;
&#xD;
        2. the impact of antibiotic resistance and cytochrome P450 C19(CYP2C19) polymorphism on the&#xD;
           eradication rate of triple therapy containing N-acetyl cysteine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Helicobacter pylori infection has been shown to be associated with the development of gastric&#xD;
      cancer and peptic ulcer diseases. Eradication of H. pylori infection could reduce the&#xD;
      occurrence or recurrence of these diseases. The triple treatment including a proton pump&#xD;
      inhibitor, clarithromycin, and amoxicillin or metronidazole to treat H pylori infection,&#xD;
      proposed at the first Maastricht conference has become universal since all the consensus&#xD;
      conferences and guidelines around the world recommended it. However, the eradication rate of&#xD;
      clarithromycin-based triple therapy has been declining in recent years, probably related to&#xD;
      the increasing resistant rate to clarithromycin. It was estimated that 15-20% of patients&#xD;
      would fail from first line standard eradication therapy and need second line rescue therapy.&#xD;
      Measures to improved H. pylori eradication rate include (1) increase treatment duration, (2)&#xD;
      add other antibiotics or use antibiotics not previously used, (3) introducing new therapeutic&#xD;
      agents, and (4) potent acid inhibition. Our group has shown the 10- or 14-day sequential&#xD;
      therapy, which consists of a proton-pump inhibitor and amoxicillin for the first 5 or 7 days,&#xD;
      followed by a proton-pump inhibitor plus clarithromycin and metronidazole (or tinidazole) for&#xD;
      another 5 or 7days, provides good eradication in first line H. pylori eradication. However,&#xD;
      complexity of sequential therapy is complex and adverse effect resulted from adding one more&#xD;
      antibiotic may have poor effect on compliance and leads to treatment failure. A simplified&#xD;
      regimen for H. pylori infection is worthy of investigation.&#xD;
&#xD;
      Introducing new therapeutic agents The H. pylori persistence in human infections and its&#xD;
      resistance to the drugs commonly used in antimicrobial therapy have been attributed not only&#xD;
      to genetic variability, but also to ability of H. pylori to form biofilm as a strategy to&#xD;
      overcome environmental stress and to protect itself. A biofilm is a dense aggregation of&#xD;
      microbial cells bound together by a slimy extracellular matrix of polysaccharide and protein.&#xD;
      When bacteria group together in these multicellular communities, they are able to tolerate&#xD;
      antimicrobial challenges that normally eradicate free-floating individual cells. It is&#xD;
      currently accepted that biofilms are implicated in over 80% of the chronic infections caused&#xD;
      by bacteria, including middle ear otitis, endocarditis, urinary tract infections and lung&#xD;
      infections of patients with cystic fibrosis. The importance of biofilm in medicine is due to&#xD;
      its role in persistence of the infection because biofilm is not removed and bacteria in&#xD;
      biofilms are 1000 more resistant to antibiotics and host defenses as compared to those free&#xD;
      living bacteria.&#xD;
&#xD;
      Several recent reports indicate that H. pylori forms biofilm either in vitro or in vivo, Cole&#xD;
      et al studied the ability of 19 H. pylori clinical isolates and reference strains in Brain&#xD;
      Heart Infusion broth supplemented with 0.1% β-cyclodextrin. Both strains were able to form&#xD;
      biofilm and the biofilm produced had a similar progression when compared to biofilm formed by&#xD;
      other bacterial species. The first evidence of in vivo biofilm formation arose in 2006. The&#xD;
      authors compared, by scanning electron microscopy, gastric biopsies from urease positive and&#xD;
      negative patients, detecting the presence of dense mature biofilm in the pathogen positive&#xD;
      biopsies while biofilm was absent in the urease negative biopsies, which is indicative that&#xD;
      H. pylori is able to form biofilm in the human gastric mucosa. To this context, it is notable&#xD;
      that stress conditions stimulate H. pylori to enter coccoid forms that when the antibiotic&#xD;
      concentration reduces, can resuscitate and repopulate the biofilm and the infection relapses.&#xD;
      In vitro study, H. pylori biofilm formation decreases the susceptibility to clarithromycin&#xD;
      and that H. pylori clarithromycin resistance mutations are more frequently generated in&#xD;
      biofilms than in planktonic cells.&#xD;
&#xD;
      Because antibacterial susceptibility of a particular strain is favored when the biofilm is&#xD;
      destabilized, it is believed that a combination of antimicrobial agents and anti-biofilm&#xD;
      molecules should be synergistic. N-acetylcysteine (NAC) being both a mucolytic agent and a&#xD;
      thiol-containing antioxidant agent was successfully used in medical practice for the&#xD;
      treatment of patients with chronic respiratory tract infections. The NAC positive effects&#xD;
      were thought to be due not only to mucus-dissolving properties, but also, interestingly, to&#xD;
      the capability to reduce and prevent biofilm formation. NAC was able to avoid biofilm&#xD;
      formation and to destabilize the already formed biofilm at concentrations over 10 mg/mL,&#xD;
      similar to results observed with other pathogens. On the other hand, in vivo studies with two&#xD;
      groups of 20 individuals each, one group (treated) received N-acetyl-cysteine for one week&#xD;
      before the anti-H. pylori treatment for refractory H. pylori infection while the other group&#xD;
      (untreated controls) did not received the destabilizing agent, showed eradication of the&#xD;
      infection in 65% of the cases for the N-acetyl-cysteine treated group as detected by the urea&#xD;
      breath test. The control group showed only 20% of successful eradication, suggesting that&#xD;
      N-acetyl-cysteine act as a biofilm destabilizing agent that favor in vivo the activity of&#xD;
      antibiotic substances.&#xD;
&#xD;
      Potent acid inhibition Acid inhibition has also proven an important component of eradication&#xD;
      therapy. The antibiotics, particularly clarithromycin, which is used against H. pylori, are&#xD;
      subject to pH-dependent degradation. This degradation is reduced by increasing gastric pH.&#xD;
      Achieving a pH above 4 maximizes the efficacy of the antibiotic. Second, proton pump&#xD;
      inhibitors (PPIs) may alter the transport of antibiotics from the plasma to the gastric juice&#xD;
      and mucosa by altering the pH or by affecting active transport processes. The minimum&#xD;
      inhibitory concentration (MIC) of the antibiotics against H. pylori is often lower at higher&#xD;
      pHs. Finally, because H. pylori is sensitive to changes in gastric pH, PPI-induced elevations&#xD;
      of pH, the gastric contents may become less hospitable to H. pylori. The importance of&#xD;
      achieving adequate acid inhibition has been highlighted by recent studies. First, increasing&#xD;
      the PPI dose was found to raise cure rates when used in dual anti-Helicobacter pylori&#xD;
      therapies. Second, a previous meta-analysis by our group showed that triple therapy using a&#xD;
      standard dose of PPI twice a day achieves higher cure rates than the same antibiotics plus&#xD;
      the PPI once daily. Previous meta-analyses show that H. pylori treatment achieves lower cure&#xD;
      rates in extensive metabolizers than in poor PPI metabolizers. All this evidence supports the&#xD;
      hypothesis that achieving a potent acid inhibition can improve cure rates of H. pylori&#xD;
      treatment.&#xD;
&#xD;
      Lansoprazole, a proton pump inhibitor that specifically inhibits H+K+-ATPase in the gastric&#xD;
      parietal cell, effectively inhibits both basal- and gastric-stimulated acid secretion. Our&#xD;
      studies have proved lansoprazole-based H. pylori eradication achieved high successful rate.&#xD;
      Dexlansoprazole modified release (MR), a new generation of proton pump inhibitor, is a novel&#xD;
      modified release formulation of dexlansoprazole, an enantiomer of lansoprazole.&#xD;
      Dexlansoprazole MR employs an innovative Dual Delayed Release (DDR) technology designed to&#xD;
      prolong the plasma concentration-time profile of dexlansoprazole and extend the duration of&#xD;
      acid suppression. In a phase 1 pharmacokinetic/pharmacodynamic study of Dexlansoprazole MR 60&#xD;
      and 90 mg once daily also produced significant increases in the percentage of time with&#xD;
      intragastric pH &gt;4 over 24-h postdose compared with lansoprazole 30 mg once daily (∼70% for&#xD;
      dexlansoprazole MR vs. 60% for lansoprazole, P &lt; 0.05). Since acid inhibition is crucial in&#xD;
      H. pylori treatment. Whether a more potent PPI, Dexlansoprazole MR could improve the efficacy&#xD;
      of H. pylori treatment has not been investigated.&#xD;
&#xD;
      Therefore, the primary purpose of the proposed study is to compare the efficacy of&#xD;
      dexlansoprazole MR based triple therapy with or without N-acetyl cysteine for helicobacter&#xD;
      pylori eradication&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">October 2016</completion_date>
  <primary_completion_date type="Anticipated">August 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Helicobacter pylori eradication rate</measure>
    <time_frame>6wks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compliance</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">654</enrollment>
  <condition>Helicobacter Pylori Infection</condition>
  <arm_group>
    <arm_group_label>Acetylcysteine + PPI-amoxicillin-clarithromycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>N-acetylcysteine 600mg bid Dexlansoprazole 60mg qd Amoxicillin 1000mg bid Clarithromycin 500mg bid All for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PPI-amoxicillin-clarithromycin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dexlansoprazole 60mg qd Amoxicillin 1000mg bid Clarithromycin 500mg bid All for 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-acetylcysteine + PPI-amoxicillin-clarithromycin</intervention_name>
    <arm_group_label>Acetylcysteine + PPI-amoxicillin-clarithromycin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PPI-amoxicillin-clarithromycin</intervention_name>
    <description>Triple therapy</description>
    <arm_group_label>PPI-amoxicillin-clarithromycin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  H. pylori infected patients who have willingness to receive eradication therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  (1) history of gastrectomy, (2)gastric malignancy, including adenocarcinoma and&#xD;
             lymphoma, (3) previous allergic reaction to antibiotics (amoxicillin, clarithromycin),&#xD;
             N-acetyl cysteine and prompt pump inhibitors (dexlansoprazole), (4)contraindication to&#xD;
             treatment drugs, (5) pregnant or lactating women, (6) severe concurrent disease. (7)&#xD;
             phenylketonuria (8) Patients who cannot give informed consent by himself or herself.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ming-Shiang Wu, MD, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chieh-Chang Chen, MD, MSc</last_name>
    <phone>886972652550</phone>
    <email>chiehchang.chen@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Internal Medicine, National Taiwan Univeristy Hospital Yun-Lin branch</name>
      <address>
        <city>Douliou City</city>
        <state>Yunlin County</state>
        <zip>640</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>National Taiwan Univeristy Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chieh-Chang Chen, MD</last_name>
    </contact>
    <investigator>
      <last_name>Jyh-Ming Liou, MD, PHD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Chieh-Chang Chen, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ming-Shiang Wu, MD, PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>September 23, 2014</last_update_submitted>
  <last_update_submitted_qc>September 23, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Taiwan University Hospital</investigator_affiliation>
    <investigator_full_name>National Taiwan University Hospital</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Helicobacter Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amoxicillin</mesh_term>
    <mesh_term>Clarithromycin</mesh_term>
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02249546
org study id: 201406074MINC
nct id: NCT02249546
lead sponsor: 
has dmc: No
Helicobacter pylori infection has been shown to be associated with the development of gastric
      cancer and peptic ulcer diseases. Eradication of H. pylori infection could reduce the
      occurence or recurrence of these diseases. The triple treatment including a proton pump
      inhibitor, clarithromycin, and amoxicillin or metronidazole to treat H pylori infection,
      proposed at the first Maastricht conference has become universal since all the consensus
      conferences and guidelines around the world recommended it. However, the eradication rate of
      clarithromycin-based triple therapy has been declining in recent years, probably related to
      the increasing resistant rate to clarithromycin. It was estimated that 15-20% of patients
      would fail from first line standard eradication therapy and need second line rescue therapy.

      The H. pylori persistence in human infections and its resistance to the drugs commonly used
      in antimicrobial therapy have been attributed not only to genetic variability, but also to
      ability of H. pylori to form biofilm as a strategy to overcome environmental stress and to
      protect itself. Several recent reports indicate that H. pylori forms biofilm either in vitro
      or in vivo, N-acetylcysteine (NAC) were thought to reduce and prevent biofilm formation. Two
      small-scale clinical trials showed NAC offers additive effect on eradication effects of H.
      pylori therapy. A recent trial showed N-acetylcysteine pre-treatment before a culture-guided
      antibiotic regimen is effective in treating refractory H. pylori infection.

      Aims: Therefore, we aim to assess

        1. Whether triple therapy containing N-acetyl cysteine is more effective than standard
           triple therapy

        2. the impact of antibiotic resistance and cytochrome P450 C19(CYP2C19) polymorphism on the
           eradication rate of triple therapy containing N-acetyl cysteine.
Helicobacter pylori infection has been shown to be associated with the development of gastric
      cancer and peptic ulcer diseases. Eradication of H. pylori infection could reduce the
      occurrence or recurrence of these diseases. The triple treatment including a proton pump
      inhibitor, clarithromycin, and amoxicillin or metronidazole to treat H pylori infection,
      proposed at the first Maastricht conference has become universal since all the consensus
      conferences and guidelines around the world recommended it. However, the eradication rate of
      clarithromycin-based triple therapy has been declining in recent years, probably related to
      the increasing resistant rate to clarithromycin. It was estimated that 15-20% of patients
      would fail from first line standard eradication therapy and need second line rescue therapy.
      Measures to improved H. pylori eradication rate include (1) increase treatment duration, (2)
      add other antibiotics or use antibiotics not previously used, (3) introducing new therapeutic
      agents, and (4) potent acid inhibition. Our group has shown the 10- or 14-day sequential
      therapy, which consists of a proton-pump inhibitor and amoxicillin for the first 5 or 7 days,
      followed by a proton-pump inhibitor plus clarithromycin and metronidazole (or tinidazole) for
      another 5 or 7days, provides good eradication in first line H. pylori eradication. However,
      complexity of sequential therapy is complex and adverse effect resulted from adding one more
      antibiotic may have poor effect on compliance and leads to treatment failure. A simplified
      regimen for H. pylori infection is worthy of investigation.

      Introducing new therapeutic agents The H. pylori persistence in human infections and its
      resistance to the drugs commonly used in antimicrobial therapy have been attributed not only
      to genetic variability, but also to ability of H. pylori to form biofilm as a strategy to
      overcome environmental stress and to protect itself. A biofilm is a dense aggregation of
      microbial cells bound together by a slimy extracellular matrix of polysaccharide and protein.
      When bacteria group together in these multicellular communities, they are able to tolerate
      antimicrobial challenges that normally eradicate free-floating individual cells. It is
      currently accepted that biofilms are implicated in over 80% of the chronic infections caused
      by bacteria, including middle ear otitis, endocarditis, urinary tract infections and lung
      infections of patients with cystic fibrosis. The importance of biofilm in medicine is due to
      its role in persistence of the infection because biofilm is not removed and bacteria in
      biofilms are 1000 more resistant to antibiotics and host defenses as compared to those free
      living bacteria.

      Several recent reports indicate that H. pylori forms biofilm either in vitro or in vivo, Cole
      et al studied the ability of 19 H. pylori clinical isolates and reference strains in Brain
      Heart Infusion broth supplemented with 0.1% β-cyclodextrin. Both strains were able to form
      biofilm and the biofilm produced had a similar progression when compared to biofilm formed by
      other bacterial species. The first evidence of in vivo biofilm formation arose in 2006. The
      authors compared, by scanning electron microscopy, gastric biopsies from urease positive and
      negative patients, detecting the presence of dense mature biofilm in the pathogen positive
      biopsies while biofilm was absent in the urease negative biopsies, which is indicative that
      H. pylori is able to form biofilm in the human gastric mucosa. To this context, it is notable
      that stress conditions stimulate H. pylori to enter coccoid forms that when the antibiotic
      concentration reduces, can resuscitate and repopulate the biofilm and the infection relapses.
      In vitro study, H. pylori biofilm formation decreases the susceptibility to clarithromycin
      and that H. pylori clarithromycin resistance mutations are more frequently generated in
      biofilms than in planktonic cells.

      Because antibacterial susceptibility of a particular strain is favored when the biofilm is
      destabilized, it is believed that a combination of antimicrobial agents and anti-biofilm
      molecules should be synergistic. N-acetylcysteine (NAC) being both a mucolytic agent and a
      thiol-containing antioxidant agent was successfully used in medical practice for the
      treatment of patients with chronic respiratory tract infections. The NAC positive effects
      were thought to be due not only to mucus-dissolving properties, but also, interestingly, to
      the capability to reduce and prevent biofilm formation. NAC was able to avoid biofilm
      formation and to destabilize the already formed biofilm at concentrations over 10 mg/mL,
      similar to results observed with other pathogens. On the other hand, in vivo studies with two
      groups of 20 individuals each, one group (treated) received N-acetyl-cysteine for one week
      before the anti-H. pylori treatment for refractory H. pylori infection while the other group
      (untreated controls) did not received the destabilizing agent, showed eradication of the
      infection in 65% of the cases for the N-acetyl-cysteine treated group as detected by the urea
      breath test. The control group showed only 20% of successful eradication, suggesting that
      N-acetyl-cysteine act as a biofilm destabilizing agent that favor in vivo the activity of
      antibiotic substances.

      Potent acid inhibition Acid inhibition has also proven an important component of eradication
      therapy. The antibiotics, particularly clarithromycin, which is used against H. pylori, are
      subject to pH-dependent degradation. This degradation is reduced by increasing gastric pH.
      Achieving a pH above 4 maximizes the efficacy of the antibiotic. Second, proton pump
      inhibitors (PPIs) may alter the transport of antibiotics from the plasma to the gastric juice
      and mucosa by altering the pH or by affecting active transport processes. The minimum
      inhibitory concentration (MIC) of the antibiotics against H. pylori is often lower at higher
      pHs. Finally, because H. pylori is sensitive to changes in gastric pH, PPI-induced elevations
      of pH, the gastric contents may become less hospitable to H. pylori. The importance of
      achieving adequate acid inhibition has been highlighted by recent studies. First, increasing
      the PPI dose was found to raise cure rates when used in dual anti-Helicobacter pylori
      therapies. Second, a previous meta-analysis by our group showed that triple therapy using a
      standard dose of PPI twice a day achieves higher cure rates than the same antibiotics plus
      the PPI once daily. Previous meta-analyses show that H. pylori treatment achieves lower cure
      rates in extensive metabolizers than in poor PPI metabolizers. All this evidence supports the
      hypothesis that achieving a potent acid inhibition can improve cure rates of H. pylori
      treatment.

      Lansoprazole, a proton pump inhibitor that specifically inhibits H+K+-ATPase in the gastric
      parietal cell, effectively inhibits both basal- and gastric-stimulated acid secretion. Our
      studies have proved lansoprazole-based H. pylori eradication achieved high successful rate.
      Dexlansoprazole modified release (MR), a new generation of proton pump inhibitor, is a novel
      modified release formulation of dexlansoprazole, an enantiomer of lansoprazole.
      Dexlansoprazole MR employs an innovative Dual Delayed Release (DDR) technology designed to
      prolong the plasma concentration-time profile of dexlansoprazole and extend the duration of
      acid suppression. In a phase 1 pharmacokinetic/pharmacodynamic study of Dexlansoprazole MR 60
      and 90 mg once daily also produced significant increases in the percentage of time with
      intragastric pH >4 over 24-h postdose compared with lansoprazole 30 mg once daily (∼70% for
      dexlansoprazole MR vs. 60% for lansoprazole, P < 0.05). Since acid inhibition is crucial in
      H. pylori treatment. Whether a more potent PPI, Dexlansoprazole MR could improve the efficacy
      of H. pylori treatment has not been investigated.

      Therefore, the primary purpose of the proposed study is to compare the efficacy of
      dexlansoprazole MR based triple therapy with or without N-acetyl cysteine for helicobacter
      pylori eradication
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Helicobacter pylori eradication rate
time frame: 6wks
measure: Compliance
time frame: 14 days
measure: Adverse effects
time frame: 14 days
arm group label: Acetylcysteine + PPI-amoxicillin-clarithromycin
arm group type: Experimental
description: N-acetylcysteine 600mg bid Dexlansoprazole 60mg qd Amoxicillin 1000mg bid Clarithromycin 500mg bid All for 14 days
arm group label: PPI-amoxicillin-clarithromycin
arm group type: Active Comparator
description: Dexlansoprazole 60mg qd Amoxicillin 1000mg bid Clarithromycin 500mg bid All for 14 days
intervention type: Drug
intervention name: N-acetylcysteine + PPI-amoxicillin-clarithromycin
arm group label: Acetylcysteine + PPI-amoxicillin-clarithromycin
intervention type: Drug
intervention name: PPI-amoxicillin-clarithromycin
description: Triple therapy
arm group label: PPI-amoxicillin-clarithromycin
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Ming-Shiang Wu, MD, PHD
role: Principal Investigator
affiliation: National Taiwan University Hospital
last name: Chieh-Chang Chen, MD, MSc
phone: 886972652550
email: chiehchang.chen@gmail.com
facility: 
status: Not yet recruiting
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: National Taiwan University Hospital
investigator full name: National Taiwan University Hospital
investigator title: Professor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Helicobacter Infections
mesh term: Amoxicillin
mesh term: Clarithromycin
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine