<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/NCT03750136</url>
  </required_header>
  <id_info>
    <org_study_id>IIKNT-001/2018</org_study_id>
    <nct_id>NCT03750136</nct_id>
  </id_info>
  <brief_title>Furosemide Alone or Unexpectedly With Solution of Hypertonic Saline in Nephrotic Syndrome</brief_title>
  <acronym>FLUSH-NS</acronym>
  <official_title>HSS (Hypertonic Saline Solution) Plus High Dose Furosemide vs High Dose Furosemide in Nephrotic Syndrome - a Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Bialystok</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Bialystok</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial will test the hypothesis that hypertonic saline on top of standard diuretic&#xD;
      treatment will help achieve adequate diuresis in patients with nephrotic syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives:&#xD;
&#xD;
      Edema is one of the major clinical manifestations of nephrotic syndrome. All patients are&#xD;
      initially treated with diuretics and sodium restriction but the results are sometimes not&#xD;
      satisfactory. Hypertonic saline solutions have been studied in congestive heart failure and a&#xD;
      meta-analysis confirmed it's role in achieving adequate diuresis and protecting patients&#xD;
      against acute kidney injury although the proposed mechanism of action is not known (osmotic&#xD;
      action?, inhibition of renin-angiotensin-aldostrerone system?, increase in renal perfusion?,&#xD;
      myocardial contractility?). The investigators therefore hypothesized that it may exert&#xD;
      beneficial effects also in nephrotic syndrome.&#xD;
&#xD;
      Treatment protocol:&#xD;
&#xD;
      A prospective placebo-controlled randomized trial. Subjects will be randomized to high-dose&#xD;
      furosemide vs high-dose furosemide plus hypertonic intravenous saline in a 1:1 fashion. All&#xD;
      subjects will receive furosemide tid (starting with 3x40 mg i.v.) with or without hypertonic&#xD;
      saline solution (3x100 ml of 3% NaCl - in a combined infusion lasting 10 minutes). Subjects&#xD;
      randomized to furosemide only will receive 3x100 ml of 5% glucose (in a combined infusion&#xD;
      lasting 10 minutes). The dose of furosemide will be determined by the investigator based on&#xD;
      patients weight, severity of edema, 24-h urine volume, kidney function. In case of poor&#xD;
      clinical response (urine volume below 1000 ml) the investigator will be able to titrate the&#xD;
      furosemide dose up to 3x180 mg i.v. All patients will be kept on low-salt diet and water&#xD;
      restriction (500-1000 ml/day), their weight will assessed every morning before breakfast and&#xD;
      measurement of 24-h urine volume will be performed every day. Additionally BNP levels will be&#xD;
      measured at baseline and after 5 days of treatment. Treatment will be continued for 5 days.&#xD;
      The primary measure of efficacy will be urine volume and the rate of acute kidney injury&#xD;
      (AKI), secondary measure of efficacy will be the expected decrease in brain natriuretic&#xD;
      peptides (BNP) levels and the length of hospitalization.&#xD;
&#xD;
      Hydrochlorothiazide, spironolactone and other diuretics use will be contraindicated during&#xD;
      the study. Patients will be required to receive standard concurrent therapy as determined by&#xD;
      their attending physician and according to current guidelines (including steroids and other&#xD;
      immunosuppresives).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 15, 2018</start_date>
  <completion_date type="Anticipated">March 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2023</primary_completion_date>
  <phase>N/A</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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Diuresis</measure>
    <time_frame>5 days</time_frame>
    <description>ml of diuresis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of hospitalisation</measure>
    <time_frame>14 days</time_frame>
    <description>days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BNP levels</measure>
    <time_frame>5 days</time_frame>
    <description>pg/ml</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Nephrotic Syndrome</condition>
  <arm_group>
    <arm_group_label>high-dose furosemide &amp; hypertonic saline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>furosemide i.v., 3% NaCl</description>
  </arm_group>
  <arm_group>
    <arm_group_label>high-dose furosemide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>furosemide i.v.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hypertonic saline</intervention_name>
    <description>high dose furosemide with hypertonic saline 3x daily</description>
    <arm_group_label>high-dose furosemide &amp; hypertonic saline</arm_group_label>
    <other_name>3% saline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Furosemide Injection</intervention_name>
    <description>high dose furosemide</description>
    <arm_group_label>high-dose furosemide</arm_group_label>
    <arm_group_label>high-dose furosemide &amp; hypertonic saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  30 consecutive patients with nephrotic syndrome (proteinuria over 3.5 g/day, edema,&#xD;
             hypoalbuminemia, dysproteinemia) admitted to II Nephrology Department from November&#xD;
             2018 onwards within 48h of admission,&#xD;
&#xD;
          -  age above 18,&#xD;
&#xD;
          -  informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  AKI (acute kidney injury) - AKIN criteria level 3,&#xD;
&#xD;
          -  CKD (chronic kidney disease) stage 4 and 5 according to KDIGO (Kidney Disease:&#xD;
             Improving Global Outcomes),&#xD;
&#xD;
          -  concomittant heart failure NYHA (New York Heart Association) class III or worse,&#xD;
&#xD;
          -  active liver disease and liver failure,&#xD;
&#xD;
          -  terminal neoplastic disease,&#xD;
&#xD;
          -  serum sodium above 145 mmol/l,&#xD;
&#xD;
          -  pregnancy.&#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>Alicja Rydzewska-Rosolowska, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Białystok</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alicja Rydzewska-Rosolowska, MD</last_name>
    <phone>+48858317885</phone>
    <email>alicja.rosolowska@umb.edu.pl</email>
  </overall_contact>
  <location>
    <facility>
      <name>II Department of Nephrology and Hypertension</name>
      <address>
        <city>Bialystok</city>
        <zip>15-276</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alicja Rydzewska-Rosolowska, MD</last_name>
      <phone>+48858317885</phone>
      <email>alicja.rosolowska@umb.edu.pl</email>
    </contact>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <reference>
    <citation>Licata G, Di Pasquale P, Parrinello G, Cardinale A, Scandurra A, Follone G, Argano C, Tuttolomondo A, Paterna S. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Am Heart J. 2003 Mar;145(3):459-66. doi: 10.1067/mhj.2003.166.</citation>
    <PMID>12660669</PMID>
  </reference>
  <reference>
    <citation>Paterna S, Parrinello G, Amato P, Dominguez L, Pinto A, Maniscalchi T, Cardinale A, Licata A, Amato V, Licata G, Di Pasquale P. Tolerability and efficacy of high-dose furosemide and small-volume hypertonic saline solution in refractory congestive heart failure. Adv Ther. 1999 Sep-Oct;16(5):219-28.</citation>
    <PMID>10915397</PMID>
  </reference>
  <reference>
    <citation>Paterna S, Di Pasquale P, Parrinello G, Amato P, Cardinale A, Follone G, Giubilato A, Licata G. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure. Eur J Heart Fail. 2000 Sep;2(3):305-13. doi: 10.1016/s1388-9842(00)00094-5.</citation>
    <PMID>10938493</PMID>
  </reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>November 19, 2022</last_update_submitted>
  <last_update_submitted_qc>November 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Bialystok</investigator_affiliation>
    <investigator_full_name>Alicja Rydzewska-Rosołowska</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>diuretics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nephrotic Syndrome</mesh_term>
    <mesh_term>Nephrosis</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Furosemide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
  </patient_data>
  <!-- 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/NCT03750136
org study id: IIKNT-001/2018
nct id: NCT03750136
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The trial will test the hypothesis that hypertonic saline on top of standard diuretic
      treatment will help achieve adequate diuresis in patients with nephrotic syndrome.
Objectives:

      Edema is one of the major clinical manifestations of nephrotic syndrome. All patients are
      initially treated with diuretics and sodium restriction but the results are sometimes not
      satisfactory. Hypertonic saline solutions have been studied in congestive heart failure and a
      meta-analysis confirmed it's role in achieving adequate diuresis and protecting patients
      against acute kidney injury although the proposed mechanism of action is not known (osmotic
      action?, inhibition of renin-angiotensin-aldostrerone system?, increase in renal perfusion?,
      myocardial contractility?). The investigators therefore hypothesized that it may exert
      beneficial effects also in nephrotic syndrome.

      Treatment protocol:

      A prospective placebo-controlled randomized trial. Subjects will be randomized to high-dose
      furosemide vs high-dose furosemide plus hypertonic intravenous saline in a 1:1 fashion. All
      subjects will receive furosemide tid (starting with 3x40 mg i.v.) with or without hypertonic
      saline solution (3x100 ml of 3% NaCl - in a combined infusion lasting 10 minutes). Subjects
      randomized to furosemide only will receive 3x100 ml of 5% glucose (in a combined infusion
      lasting 10 minutes). The dose of furosemide will be determined by the investigator based on
      patients weight, severity of edema, 24-h urine volume, kidney function. In case of poor
      clinical response (urine volume below 1000 ml) the investigator will be able to titrate the
      furosemide dose up to 3x180 mg i.v. All patients will be kept on low-salt diet and water
      restriction (500-1000 ml/day), their weight will assessed every morning before breakfast and
      measurement of 24-h urine volume will be performed every day. Additionally BNP levels will be
      measured at baseline and after 5 days of treatment. Treatment will be continued for 5 days.
      The primary measure of efficacy will be urine volume and the rate of acute kidney injury
      (AKI), secondary measure of efficacy will be the expected decrease in brain natriuretic
      peptides (BNP) levels and the length of hospitalization.

      Hydrochlorothiazide, spironolactone and other diuretics use will be contraindicated during
      the study. Patients will be required to receive standard concurrent therapy as determined by
      their attending physician and according to current guidelines (including steroids and other
      immunosuppresives).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Diuresis
time frame: 5 days
description: ml of diuresis
measure: Length of hospitalisation
time frame: 14 days
description: days
measure: BNP levels
time frame: 5 days
description: pg/ml
arm group label: high-dose furosemide & hypertonic saline
arm group type: Experimental
description: furosemide i.v., 3% NaCl
arm group label: high-dose furosemide
arm group type: Active Comparator
description: furosemide i.v.
intervention type: Drug
intervention name: Hypertonic saline
description: high dose furosemide with hypertonic saline 3x daily
arm group label: high-dose furosemide & hypertonic saline
other name: 3% saline
intervention type: Drug
intervention name: Furosemide Injection
description: high dose furosemide
arm group label: high-dose furosemide
arm group label: high-dose furosemide & hypertonic saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alicja Rydzewska-Rosolowska, MD
role: Principal Investigator
affiliation: Medical University of Białystok
last name: Alicja Rydzewska-Rosolowska, MD
phone: +48858317885
email: alicja.rosolowska@umb.edu.pl
facility: 
status: Recruiting
contact: 
country: Poland
citation: Licata G, Di Pasquale P, Parrinello G, Cardinale A, Scandurra A, Follone G, Argano C, Tuttolomondo A, Paterna S. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Am Heart J. 2003 Mar;145(3):459-66. doi: 10.1067/mhj.2003.166.
PMID: 12660669
citation: Paterna S, Parrinello G, Amato P, Dominguez L, Pinto A, Maniscalchi T, Cardinale A, Licata A, Amato V, Licata G, Di Pasquale P. Tolerability and efficacy of high-dose furosemide and small-volume hypertonic saline solution in refractory congestive heart failure. Adv Ther. 1999 Sep-Oct;16(5):219-28.
PMID: 10915397
citation: Paterna S, Di Pasquale P, Parrinello G, Amato P, Cardinale A, Follone G, Giubilato A, Licata G. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure. Eur J Heart Fail. 2000 Sep;2(3):305-13. doi: 10.1016/s1388-9842(00)00094-5.
PMID: 10938493
responsible party type: Principal Investigator
investigator affiliation: Medical University of Bialystok
investigator full name: Alicja Rydzewska-Rosołowska
investigator title: Principal Investigator
mesh term: Nephrotic Syndrome
mesh term: Nephrosis
mesh term: Syndrome
mesh term: Furosemide
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code