xml: <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/NCT05965934</url>
    </required_header>
    <id_info>
      <org_study_id>2022-CHF-012</org_study_id>
      <nct_id>NCT05965934</nct_id>
    </id_info>
    <brief_title>Management of Volume Overload HF Patients by Individual DSR Treatment adJustment-a clinicAl inVestigation of InfusatE2.0</brief_title>
    <acronym>MOJAVE</acronym>
    <official_title>A Prospective, Randomized Study of Infusate 2.0 Direct Sodium Removal (DSR) Treatment in Subjects With Chronic Heart Failure (CHF) Induced Persistent Congestion, Resistant to Loop Diuretic Treatment.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sequana Medical N.V.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sequana Medical N.V.</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study is a multi-center, prospective, randomized (2:1), open-label study to evaluate the&#xD;
        safety and efficacy of DSR therapy using the Infusate 2.0 peritoneal solution (composed of&#xD;
        30% icodextrin and 10% dextrose) in diuretic resistant patients with HF and persistent volume&#xD;
        overload.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study will start with a non-randomized cohort in which 3 eligible subjects will be&#xD;
        treated with Infusate 2.0 on top of their usual care while all loop diuretic treatment is&#xD;
        stopped. A Peritoneal Dialysis (PD) catheter will be implanted to administer the infusate 14&#xD;
        days post-PD catheter implantation. The infusate will be drained via the same route after up&#xD;
        to 24 hr dwell time. This DSR process will be repeated up to daily over a treatment period of&#xD;
        4 weeks (D1-D28). The quantity of infusate and the duration of dwell time will be adjusted&#xD;
        based on treatment effect and tolerability.&#xD;
  &#xD;
        After the treatment period, the PD catheter is removed and a 3 month safety follow-up period&#xD;
        starts to the end of study (D29-D120).&#xD;
  &#xD;
        After Data and Safety Monitoring Board (DSMB) review of 30 days follow-up data (D58) of the&#xD;
        non-randomized cohort and DSMB approval to proceed, the 2:1 randomized enrollment of up to 30&#xD;
        additional subjects will be opened.&#xD;
  &#xD;
          -  DSR Group (N = 20) Treatment: DSR Infusate 2.0 DSR is to be started 14 days post-PD&#xD;
             catheter implantation (= D1) for a period of 4 weeks (D28) on top of optimized usual&#xD;
             care for HF, while loop diuretic treatment is suspended.&#xD;
  &#xD;
          -  Control Group (N = 10) Treatment: Optimized usual care for HF IV loop diuretic treatment&#xD;
             is to be started (or continued) after a 14 days observation period (= D1) and can be&#xD;
             continued for up to 4 weeks (D28).&#xD;
  &#xD;
        All subjects should then enter the 3 month safety follow-up period (D29-D120) until the end&#xD;
        of study (D120).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 7, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>Phase 1/Phase 2</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>Adverse event rate through end of treatment period</measure>
      <time_frame>from Day 1 to day 28 (treatment period)</time_frame>
      <description>Safety</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Serious adverse event rate through end of treatment period</measure>
      <time_frame>from Day 1 to day 28 (treatment period)</time_frame>
      <description>Safety</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Urine sodium output from baseline to end of treatment period</measure>
      <time_frame>from Day 1 to day 28 (treatment period)</time_frame>
      <description>Efficacy</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">33</enrollment>
    <condition>Heart Failure</condition>
    <condition>Volume Overload</condition>
    <arm_group>
      <arm_group_label>Direct Sodium Removal (DSR) Infusate 2.0</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive a peritoneal dialysis catheter implant. DSR is to be started 14 days after catheter implantation (= D1) for a period of 4 weeks (D28) on top of optimized usual care for HF, while loop diuretic treatment is suspended. Participants then enter enter a 3 month safety follow-up period (D29-D120) until the end of study (D120).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Optimized Usual Care for HF</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>IV loop diuretic treatment is to be started (or continued) after a 14 days observation period (= D1) and can be continued for up to 4 weeks (D28). Participants then enter enter a 3 month safety follow-up period (D29-D120) until the end of study (D120).</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Direct Sodium Removal Infusate 2.0</intervention_name>
      <description>Direct Sodium Removal via peritoneal ultrafiltration using Infusate 2.0 (30% icodextrin, 10% dextrose). Patients (if not yet on SGLT-2 inhibitors) will receive SGLT-2 inhibitors.</description>
      <arm_group_label>Direct Sodium Removal (DSR) Infusate 2.0</arm_group_label>
      <other_name>SGLT-2 inhibitor (dapagliflozin)</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Aged ≥18 years at screening&#xD;
  &#xD;
            -  Weight at screening ≥50 kg (110 lbs)&#xD;
  &#xD;
            -  Creatinine-based estimated glomerular filtration rate (eGFR) (CKD-EPI] 2021 formula)&#xD;
               ≥30 mL/min/1.73m² at screening&#xD;
  &#xD;
            -  6-hour cumulative urine sodium excretion &lt;100 mmol to 40 mg IV furosemide on diuretic&#xD;
               challenge&#xD;
  &#xD;
            -  Diagnosis of symptomatic heart failure with NYHA class III or IV AND daily diuretic&#xD;
               dose ≥80 mg furosemide (or ≥20 mg torsemide or ≥1 mg bumetanide) for ≥14 days prior to&#xD;
               screening AND NT-proBNP &gt;2000 pg/mL (or BNP &gt;400 pg/mL) OR oral daily diuretic dose&#xD;
               ≥160 mg furosemide (or ≥40 mg torsemide or ≥2 mg bumetanide) over the previous 14 days&#xD;
               AND ≥2 HF volume overload events within the last 6 months prior to screening or 2 HF&#xD;
               volume overload-related hospitalizations within the last 12 months prior to screening&#xD;
  &#xD;
            -  Persistent mild to moderate volume overload with ≥2,3 kg (5 lbs) of excess&#xD;
               hypervolemia AND more than trace peripheral edema AND/OR jugular venous distention&#xD;
               AND/OR elevated filling pressure on chronic remote pressure monitoring device&#xD;
  &#xD;
            -  Systolic blood pressure ≥90 mmHg and &lt;180 mmHg&#xD;
  &#xD;
            -  Receiving maximally tolerated stable doses of guideline-directed medical therapy&#xD;
               (GDMT)&#xD;
  &#xD;
            -  For participants of childbearing potential: negative pregnancy test and agreement to&#xD;
               use highly effective contraception for ≥1 month prior to screening and until ≥3 months&#xD;
               after last exposure to investigational medicinal product&#xD;
  &#xD;
            -  For participants with intimate partners of childbearing potential: agreement to use&#xD;
               highly effective contraception for ≥1 month prior to screening and until ≥3 months&#xD;
               after last exposure to investigational medicinal product&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Reversible cause of persistent decompensation or diuretic resistance&#xD;
  &#xD;
            -  Contraindications for peritoneal dialysis (PD) or PD catheter placement&#xD;
  &#xD;
            -  Known contraindication to icodextrin use&#xD;
  &#xD;
            -  Known contraindication or intolerance or allergy to SGLT2 inhibitors&#xD;
  &#xD;
            -  Current diagnosis of severe bladder dysfunction&#xD;
  &#xD;
            -  Imminent need for hospitalization&#xD;
  &#xD;
            -  Current or prior (past 6 months) use of renal replacement therapy&#xD;
  &#xD;
            -  Anemia with hemoglobin &lt;8 g/dL&#xD;
  &#xD;
            -  Serum sodium &lt;130 mEq/L&#xD;
  &#xD;
            -  Severe albuminuria (urinary albumin/creatinine ratio &gt;1 at screening)&#xD;
  &#xD;
            -  Severe cardiac cachexia&#xD;
  &#xD;
            -  Clinically significant cirrhosis or history of clinically significant ascites (i.e.,&#xD;
               prior large volume paracentesis) or large volume ascites on imaging or exam&#xD;
  &#xD;
            -  Type 1 diabetes, uncontrolled Type 2 diabetes, &quot;brittle&quot; diabetes or frequent&#xD;
               hypoglycemia or severe hyperglycemic episodes requiring emergent intervention in the&#xD;
               last 6 months&#xD;
  &#xD;
            -  Known or suspected low output HF&#xD;
  &#xD;
            -  Prior or planned heart transplant or mechanical cardiac support implantation (LVAD)&#xD;
  &#xD;
            -  History of severe hyperkalemia &gt; 5.5 mEq/L (past 6 months) or screening plasma&#xD;
               potassium &gt;4.5 mEq/L&#xD;
  &#xD;
            -  Significant non-cardiac disease or comorbidities expected to reduce life expectancy to&#xD;
               &lt;1 year or to interfere with safety or conduct of the study&#xD;
  &#xD;
            -  Severe restrictive or obstructive HF or hemodynamically significant, severe&#xD;
               uncorrected stenotic valvular disease&#xD;
  &#xD;
            -  Receiving anticoagulation or antiplatelet treatment, which cannot be withheld&#xD;
               (bridging therapy allowed)&#xD;
  &#xD;
            -  Recent myocardial infarction, cerebrovascular accident, transient ischemic attack,&#xD;
               coronary revascularization, arrhythmia ablation, cardiac resynchronization therapy, or&#xD;
               surgical or transcatheter valve intervention (within 90 days prior to screening)&#xD;
  &#xD;
            -  Received treatment with other investigational products or devices within 30 days of&#xD;
               screening or 5 halflives of the previous investigational product&#xD;
  &#xD;
            -  Pregnancy or lactation&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jeffrey Turner, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Yale Universtiry</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Marath Fudim, MD MHS</last_name>
      <role>Principal Investigator</role>
      <affiliation>Duke University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jeroen Capel</last_name>
      <phone>+41 444 03 55 12</phone>
      <email>Jeroen.capel@sequanamedical.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Oliver Goedje</last_name>
      <phone>+32 9 292 80 65</phone>
      <email>oliver.goedje@sequanamedical.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Yale University</name>
        <address>
          <city>New Haven</city>
          <state>Connecticut</state>
          <zip>06510</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jeffrey Turner, MD</last_name>
        <phone>203-785-2020</phone>
        <email>jeffrey.turner@yale.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 13, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Direct Sodium Removal</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Heart Failure</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dapagliflozin</mesh_term>
      <mesh_term>Sodium-Glucose Transporter 2 Inhibitors</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05965934
  org study id: 2022-CHF-012
  nct id: NCT05965934
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This study is a multi-center, prospective, randomized (2:1), open-label study to evaluate the
        safety and efficacy of DSR therapy using the Infusate 2.0 peritoneal solution (composed of
        30% icodextrin and 10% dextrose) in diuretic resistant patients with HF and persistent volume
        overload.
  The study will start with a non-randomized cohort in which 3 eligible subjects will be
        treated with Infusate 2.0 on top of their usual care while all loop diuretic treatment is
        stopped. A Peritoneal Dialysis (PD) catheter will be implanted to administer the infusate 14
        days post-PD catheter implantation. The infusate will be drained via the same route after up
        to 24 hr dwell time. This DSR process will be repeated up to daily over a treatment period of
        4 weeks (D1-D28). The quantity of infusate and the duration of dwell time will be adjusted
        based on treatment effect and tolerability.
  
        After the treatment period, the PD catheter is removed and a 3 month safety follow-up period
        starts to the end of study (D29-D120).
  
        After Data and Safety Monitoring Board (DSMB) review of 30 days follow-up data (D58) of the
        non-randomized cohort and DSMB approval to proceed, the 2:1 randomized enrollment of up to 30
        additional subjects will be opened.
  
          -  DSR Group (N = 20) Treatment: DSR Infusate 2.0 DSR is to be started 14 days post-PD
             catheter implantation (= D1) for a period of 4 weeks (D28) on top of optimized usual
             care for HF, while loop diuretic treatment is suspended.
  
          -  Control Group (N = 10) Treatment: Optimized usual care for HF IV loop diuretic treatment
             is to be started (or continued) after a 14 days observation period (= D1) and can be
             continued for up to 4 weeks (D28).
  
        All subjects should then enter the 3 month safety follow-up period (D29-D120) until the end
        of study (D120).
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Adverse event rate through end of treatment period
  time frame: from Day 1 to day 28 (treatment period)
  description: Safety
  measure: Serious adverse event rate through end of treatment period
  time frame: from Day 1 to day 28 (treatment period)
  description: Safety
  measure: Change in Urine sodium output from baseline to end of treatment period
  time frame: from Day 1 to day 28 (treatment period)
  description: Efficacy
  arm group label: Direct Sodium Removal (DSR) Infusate 2.0
  arm group type: Experimental
  description: Participants will receive a peritoneal dialysis catheter implant. DSR is to be started 14 days after catheter implantation (= D1) for a period of 4 weeks (D28) on top of optimized usual care for HF, while loop diuretic treatment is suspended. Participants then enter enter a 3 month safety follow-up period (D29-D120) until the end of study (D120).
  arm group label: Optimized Usual Care for HF
  arm group type: No Intervention
  description: IV loop diuretic treatment is to be started (or continued) after a 14 days observation period (= D1) and can be continued for up to 4 weeks (D28). Participants then enter enter a 3 month safety follow-up period (D29-D120) until the end of study (D120).
  intervention type: Drug
  intervention name: Direct Sodium Removal Infusate 2.0
  description: Direct Sodium Removal via peritoneal ultrafiltration using Infusate 2.0 (30% icodextrin, 10% dextrose). Patients (if not yet on SGLT-2 inhibitors) will receive SGLT-2 inhibitors.
  arm group label: Direct Sodium Removal (DSR) Infusate 2.0
  other name: SGLT-2 inhibitor (dapagliflozin)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Jeffrey Turner, MD
  role: Principal Investigator
  affiliation: Yale Universtiry
  last name: Marath Fudim, MD MHS
  role: Principal Investigator
  affiliation: Duke University
  last name: Jeroen Capel
  phone: +41 444 03 55 12
  email: Jeroen.capel@sequanamedical.com
  last name: Oliver Goedje
  phone: +32 9 292 80 65
  email: oliver.goedje@sequanamedical.com
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Sponsor
  mesh term: Heart Failure
  mesh term: Dapagliflozin
  mesh term: Sodium-Glucose Transporter 2 Inhibitors