<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/NCT02975726</url>
  </required_header>
  <id_info>
    <org_study_id>B2014:066</org_study_id>
    <nct_id>NCT02975726</nct_id>
  </id_info>
  <brief_title>Peritoneal Dialysis Catheters for the Treatment of Refractory Ascites</brief_title>
  <official_title>Peritoneal Dialysis Catheters for the Treatment of Refractory Ascites Management: A Randomized Un-Blinded Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Manitoba</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Manitoba</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      One complication of liver disease is the buildup of fluid within the belly. This is known as&#xD;
      ascites. Patients who have ascites have a decreased appetite, pain, nausea and shortness of&#xD;
      breath. Ascites is typically treated with medications, however when that does not work,&#xD;
      patients need a procedure where a needle is inserted in the belly every few weeks to drain&#xD;
      the excess fluid. About 2 in 5 patients with ascites from liver failure can get kidney&#xD;
      disease from their worsening liver function or from the drainage of fluid with needles. Once&#xD;
      patients have both advanced liver disease and kidney disease, their chance of dying largely&#xD;
      increases.&#xD;
&#xD;
      The present study will be the first of its kind to study a new technique to treat ascites.&#xD;
      Investigators are planning to place a tube in a patient's belly to drain the excessive&#xD;
      amounts of fluid. This technique is similar to how one type of dialysis is done to treat&#xD;
      patients with kidney failure. This study is set as a pilot investigation in order to&#xD;
      determine the feasibility of doing a larger, randomized clinical trial investigating the use&#xD;
      of this novel technique. Importantly, advanced liver disease patients are at high risk to&#xD;
      develop kidney disease, and therefore are an important group to focus on. Investigators&#xD;
      believe that this technique will prevent or slow the development of kidney disease in liver&#xD;
      failure patients, and improve their quality of life, far more than the current available&#xD;
      treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Refractory ascites is when fluid recurrently accumulates in the peritoneal cavity, as an end&#xD;
      result of multiple mechanisms, including liver cirrhosis, peritoneal infiltration by tumor,&#xD;
      portal hypertension, lymphangitic carcinomatosis, congestive heart failure, or lymphatic&#xD;
      obstruction. It is associated with increased mortality and morbidity, including complications&#xD;
      of abdominal wall hernias, spontaneous bacterial peritonitis, kidney dysfunction, and pleural&#xD;
      effusions. The development of ascites also leads to multiple symptoms including anorexia,&#xD;
      early satiety, nausea and vomiting, shortness of breath, and limited mobility.&#xD;
&#xD;
      The management of ascites associated with liver dysfunction usually follows a stepwise&#xD;
      escalation in treatments. The initial management typically involves sodium restriction and&#xD;
      diuretic therapy up to a daily maximum of 160 mg of furosemide and 400 mg of spironolactone.&#xD;
      When ascites no longer can be controlled by these measures, one option is to decrease portal&#xD;
      hypertension, a main pathogenic factor in ascites development, by undergoing a procedure&#xD;
      called transjugular intrahepatic portosystemic shunt (TIPS). This procedure requires certain&#xD;
      patient criteria to be fulfilled and is associated with complications and increased risk of&#xD;
      hepatic encephalopathy, and therefore is confined to a small subgroup of patients with&#xD;
      ascites. Consequently, abdominal large volume paracentesis (LVP) is the treatment of choice&#xD;
      in many patients. This procedure involves insertion of a needle into the peritoneal cavity&#xD;
      where ascites accumulates, then attaching the needle to a collection system that drains the&#xD;
      ascites by gravity. The definitive treatment for ascites in patients with cirrhosis is a&#xD;
      liver transplant, but due to limited supply of organs, and contraindications to&#xD;
      transplantation, patients often undergo repeated LVP while waiting on the wait list or until&#xD;
      death. Paracentesis is associated with risks including post paracentesis circulatory&#xD;
      dysfunction leading to hyponatremia, kidney dysfunction, viscus puncture, and peritonitis. It&#xD;
      also is a costly, resource intense, and at times an uncomfortable treatment for patients due&#xD;
      to the procedure itself and the need for repeated treatments.&#xD;
&#xD;
      A potential alternative to LVP is the placement of an intraperitoneal catheter, in the same&#xD;
      manner that a peritoneal dialysis (PD) catheter, to drain ascites. The procedure has a high&#xD;
      technical insertion success rate with minimal complications and is routinely done at the&#xD;
      bedside by nephrologist under local anesthesia. PD catheter placement for ascites drainage&#xD;
      has many potential advantages, including the ability for it to be done at home by the patient&#xD;
      and avoid visits to clinics or hospitals; the frequency of drainage can be timed to patient&#xD;
      symptoms, and perhaps have less complication rates than LVP. However, the efficacy and safety&#xD;
      of this approach in decompensated cirrhosis when compared to periodic LVP (current standard&#xD;
      of care) has not been tested in a randomized trial. Investigators propose a single center,&#xD;
      multi-site randomized control trial comparing bedside PD catheter placement versus usual&#xD;
      standard of serial LVP for treatment of refractory ascites. The primary outcomes will be&#xD;
      improvement of 10 points in the physical component score (PCS) of the Short Form-36 (SF-36)&#xD;
      at two months. Investigators plan to randomize 50 patients (25 per arm) based on a power&#xD;
      calculation to achieve an 10 point improvement in the PCS-SF-36 (SE = 5). Secondary outcomes&#xD;
      will include incidence of mechanical and infectious complications, emergency department&#xD;
      utilization, hospitalization and mortality, all other domains of the SF-36, Euroquol-5D&#xD;
      (EQ-5D), the Newcastle Patient Reported Ascites Measure and overall health care costs.&#xD;
&#xD;
      Primary Hypothesis: Drainage of ascites associated with liver failure via PD catheter is&#xD;
      superior to serial LVP in improving the physical component of quality of life as measured by&#xD;
      SF-36.&#xD;
&#xD;
      This trial will be pivotal in possibly changing the standard of care for the management of&#xD;
      refractory ascites from cirrhosis. If the primary hypothesis is confirmed, investigators will&#xD;
      design and conduct subsequent trials to address potential morbidity and mortality benefits&#xD;
      associated with this technique for ascites management.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">February 2019</completion_date>
  <primary_completion_date type="Actual">May 2018</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the physical component of Quality of Life</measure>
    <time_frame>2 months post intervention</time_frame>
    <description>Change in the physical component summary score of the SF 36 questionnaire.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Catheter Insertion Technical Success Rate</measure>
    <time_frame>Day of insertion of PD catheter</time_frame>
    <description>Technical success rate of tunneled PD catheters: Defined as successful positioning of the catheter in the intraperitoneal space with initial drainage of ascites</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD Catheter Survival</measure>
    <time_frame>Number of days between catheter insertion and possible complication, up to 6 months</time_frame>
    <description>Defined as days from insertion to date of a PD catheter related complication if they occur, assessed during the study timeframe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD Catheter Related Complications Frequency</measure>
    <time_frame>through study completion, up to 6 months</time_frame>
    <description>The number of participants with following complications: 1) Infection at the exit site or tunnel (as defined by the International Society of peritoneal Dialysis 2010 guidelines). 2) Peritonitis 3) intra-luminal/extra-luminal obstruction 4) catheter mal positioning (migration, omental wrapping) 5) Catheter leakage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Large Volume Paracentesis Complications Frequency</measure>
    <time_frame>through study completion, up to 6 months</time_frame>
    <description>The number of participants with following complications: 1) Peritonitis 2) leakage at puncture site 3) visceral puncture</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant Self-Reported Health Status</measure>
    <time_frame>0,2,4 and 6 months</time_frame>
    <description>Measured by the number of points as a result of participants' answers to SF-36 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant Health State Description and Evaluation</measure>
    <time_frame>0,2,4 and 6 months</time_frame>
    <description>Measured by the number of points as a result of participants' answers to EQ-5D questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Impact of Ascites on Health Related Quality of Life</measure>
    <time_frame>0,2,4 and 6 months</time_frame>
    <description>Measured by the number of points as a result of participants' answers to Newcastle Patient Reported Ascites Measure questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal Dysfunction Assessment</measure>
    <time_frame>Monthly, up to 6 months</time_frame>
    <description>Measured by blood work: serum creatinine, serum sodium, potassium, chloride, bicarbonate, urea, glucose, eGFR (estimated glomerular filtration rate).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal Function Assessment</measure>
    <time_frame>at 0 and 6 months</time_frame>
    <description>Measured by 24 hour urine collection: creatinine clearance, urine volume and urine sodium.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Albumin and PD Fluid Albumin Assesment</measure>
    <time_frame>At 0, 2, and 6 months</time_frame>
    <description>PD catheter arm: Assessment of serum albumin and measurement of albumin in PD fluid at 0, 2, and 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Heart Rate</measure>
    <time_frame>At regular clinic appointments, through study completion, up to 6 months</time_frame>
    <description>Patient heart rate taken as part of regular physical assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Blood Pressure</measure>
    <time_frame>At regular clinic appointments, through study completion, up to 6 months</time_frame>
    <description>Patient blood pressure taken as part of regular physical assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Weight</measure>
    <time_frame>At regular clinic appointments, through study completion, up to 6 months</time_frame>
    <description>Patient weight taken as part of regular physical assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Visits</measure>
    <time_frame>through study completion, up to 6 months</time_frame>
    <description>The number of hospital admissions or emergency department visits from complications related to cirrhosis (encephalopathy, gastrointestinal bleed) or peritonitis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Health Care Costs</measure>
    <time_frame>through study completion, up to 6 months</time_frame>
    <description>Direct health care costs will be estimated for both groups of patients taking a health care payor perspective.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost Effectiveness</measure>
    <time_frame>through study completion, up to 6 months</time_frame>
    <description>A decision analysis, Markov model will be constructed between the two intervention arms with outcomes expressed as cost per quality adjusted live year (cost per QALY) and expressed as incremental cost effectiveness ratios (ICER's).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Liver Cirrhosis</condition>
  <condition>Ascites</condition>
  <arm_group>
    <arm_group_label>Peritoneal Dialysis Catheter Insertion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Catheters will be inserted at the bedside in a special procedure room.Argyle PD catheter kits will be used:2 cuffed curled catheters at 57cm or 62cm lengths. At time of PD catheter insertion,most patients will be drained of 5-10L of ascites or more to decrease the chance of catheter leaks.The volume removed will be at sole discretion of physician doing the procedure.Patients will be administered 25% Human Serum Albumin injection: 100cc after the 5-10L drainage,and 200cc if 10-15L is removed.Patients will undergo an initial drain and training with a specialized nurse.Patients in this arm will be instructed to drain a maximum of 2L per day after the initial drain.Monthly bloodwork will be performed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Large Volume Paracentesis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in this arm of the study will continue their usual practice of LVP as required. They will continue to undergo their LVP procedures through their regular means.Monthly bloodwork will be performed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Peritoneal Dialysis Catheter</intervention_name>
    <description>Peritoneal dialysis catheter insertion in order to drain access fluid within the belly for patients with liver cirrhosis and refractory ascites.</description>
    <arm_group_label>Peritoneal Dialysis Catheter Insertion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Large Volume Paracentesis</intervention_name>
    <description>Insertion of a needle into the peritoneal cavity where ascites accumulates, then attaching the needle to a collection system that drains the ascites by gravity. This procedure is part of the standard care for the treatment of refractory ascites.</description>
    <arm_group_label>Large Volume Paracentesis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>25% Human Serum Albumin injection</intervention_name>
    <description>Patients will be given Human Serum Albumin after the initial drain of ascites fluid: 100cc for 5-10L drainage, 200cc for 10-15L drainage.</description>
    <arm_group_label>Peritoneal Dialysis Catheter Insertion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Bloodwork</intervention_name>
    <description>Monthly bloodwork will be done as part of usual standard of care.</description>
    <arm_group_label>Large Volume Paracentesis</arm_group_label>
    <arm_group_label>Peritoneal Dialysis Catheter Insertion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and non-pregnant females greater than 18 years of age.&#xD;
&#xD;
          2. Liver cirrhosis as defined by a histological, clinical, or radiological criteria&#xD;
&#xD;
          3. Patients with refractory non-malignant ascites requiring 2 or more LVPs in the last 4&#xD;
             months.&#xD;
&#xD;
          4. No contraindication for bedside PD catheter insertion (e.g. prior major abdominal&#xD;
             surgery, ostomies, large hernias, bleeding diatheses, inability to lie flat).&#xD;
&#xD;
          5. Patients having a support person (family member/friend/caregiver, etc) willing to go&#xD;
             through training and help with catheter care.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior liver transplant&#xD;
&#xD;
          2. Is actively being worked up for liver transplant or is already on the liver transplant&#xD;
             waitlist&#xD;
&#xD;
          3. Current SBP (spontaneous bacterial peritonitis) defined as polymorphonuclear (PMN)&#xD;
             cell count of &gt;250 cells/mm3 in the ascites or positive bacteria in ascitic cultures&#xD;
&#xD;
          4. Malignant ascites&#xD;
&#xD;
          5. Severe coagulopathy with either an INR (international normalized ratio) &gt; 1.5, a&#xD;
             platelet count &lt; 50 x 109/L that is not able to be reversed at time of PD catheter&#xD;
             insertion&#xD;
&#xD;
          6. Any previous episodes of spontaneous bacterial peritonitis.&#xD;
&#xD;
          7. Loculated ascites&#xD;
&#xD;
          8. Known presence of HIV/AIDS&#xD;
&#xD;
          9. Immunomodulatory treatments used within the last 4 months&#xD;
&#xD;
         10. Expected survival &lt;6 months and/or MELD (The Model for End-Stage Liver Disease) score&#xD;
             &gt; 30&#xD;
&#xD;
         11. Hepatic Encephalopathy episode requiring hospital admission in the past 6 months.&#xD;
&#xD;
         12. History of non-compliance or suspected failure to comply with study requirements&#xD;
&#xD;
         13. Allergies to Vancomycin and Cephalosporins.&#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>Paul Komenda, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Manitoba</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Health Sciences Centre</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R3E 3P4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Senousy BE, Draganov PV. Evaluation and management of patients with refractory ascites. World J Gastroenterol. 2009 Jan 7;15(1):67-80. doi: 10.3748/wjg.15.67.</citation>
    <PMID>19115470</PMID>
  </reference>
  <reference>
    <citation>Planas R, Montoliu S, Balleste B, Rivera M, Miquel M, Masnou H, Galeras JA, Gimenez MD, Santos J, Cirera I, Morillas RM, Coll S, Sola R. Natural history of patients hospitalized for management of cirrhotic ascites. Clin Gastroenterol Hepatol. 2006 Nov;4(11):1385-94. doi: 10.1016/j.cgh.2006.08.007.</citation>
    <PMID>17081806</PMID>
  </reference>
  <reference>
    <citation>Singhal S, Baikati KK, Jabbour II, Anand S. Management of refractory ascites. Am J Ther. 2012 Mar;19(2):121-32. doi: 10.1097/MJT.0b013e3181ff7a8b.</citation>
    <PMID>21192246</PMID>
  </reference>
  <reference>
    <citation>Runyon BA; AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009 Jun;49(6):2087-107. doi: 10.1002/hep.22853. No abstract available.</citation>
    <PMID>19475696</PMID>
  </reference>
  <reference>
    <citation>Van Thiel DH, Moore CM, Garcia M, George M, Nadir A. Continuous peritoneal drainage of large-volume ascites. Dig Dis Sci. 2011 Sep;56(9):2723-7. doi: 10.1007/s10620-011-1792-x. Epub 2011 Jul 7.</citation>
    <PMID>21735084</PMID>
  </reference>
  <reference>
    <citation>Peltekian KM, Wong F, Liu PP, Logan AG, Sherman M, Blendis LM. Cardiovascular, renal, and neurohumoral responses to single large-volume paracentesis in patients with cirrhosis and diuretic-resistant ascites. Am J Gastroenterol. 1997 Mar;92(3):394-9.</citation>
    <PMID>9068457</PMID>
  </reference>
  <reference>
    <citation>Lungren MP, Kim CY, Stewart JK, Smith TP, Miller MJ. Tunneled peritoneal drainage catheter placement for refractory ascites: single-center experience in 188 patients. J Vasc Interv Radiol. 2013 Sep;24(9):1303-8. doi: 10.1016/j.jvir.2013.05.042. Epub 2013 Jul 19.</citation>
    <PMID>23876552</PMID>
  </reference>
  <reference>
    <citation>Savin MA, Kirsch MJ, Romano WJ, Wang SK, Arpasi PJ, Mazon CD. Peritoneal ports for treatment of intractable ascites. J Vasc Interv Radiol. 2005 Mar;16(3):363-8. doi: 10.1097/01.RVI.0000147082.05392.2B.</citation>
    <PMID>15758132</PMID>
  </reference>
  <reference>
    <citation>Tapping CR, Ling L, Razack A. PleurX drain use in the management of malignant ascites: safety, complications, long-term patency and factors predictive of success. Br J Radiol. 2012 May;85(1013):623-8. doi: 10.1259/bjr/24538524. Epub 2011 Mar 22.</citation>
    <PMID>21427184</PMID>
  </reference>
  <reference>
    <citation>Barnett TD, Rubins J. Placement of a permanent tunneled peritoneal drainage catheter for palliation of malignant ascites: a simplified percutaneous approach. J Vasc Interv Radiol. 2002 Apr;13(4):379-83. doi: 10.1016/s1051-0443(07)61740-0.</citation>
    <PMID>11932368</PMID>
  </reference>
  <reference>
    <citation>Belfort MA, Stevens PJ, DeHaek K, Soeters R, Krige JE. A new approach to the management of malignant ascites; a permanently implanted abdominal drain. Eur J Surg Oncol. 1990 Feb;16(1):47-53.</citation>
    <PMID>1689678</PMID>
  </reference>
  <reference>
    <citation>Monsky WL, Yoneda KY, MacMillan J, Deutsch LS, Dong P, Hourigan H, Schwartz Y, Magee S, Duffield C, Boak T, Cernilia J. Peritoneal and pleural ports for management of refractory ascites and pleural effusions: assessment of impact on patient quality of life and hospice/home nursing care. J Palliat Med. 2009 Sep;12(9):811-7. doi: 10.1089/jpm.2009.0061.</citation>
    <PMID>19622018</PMID>
  </reference>
  <reference>
    <citation>Fleming ND, Alvarez-Secord A, Von Gruenigen V, Miller MJ, Abernethy AP. Indwelling catheters for the management of refractory malignant ascites: a systematic literature overview and retrospective chart review. J Pain Symptom Manage. 2009 Sep;38(3):341-9. doi: 10.1016/j.jpainsymman.2008.09.008. Epub 2009 Mar 28.</citation>
    <PMID>19328648</PMID>
  </reference>
  <reference>
    <citation>Nessim SJ, Bargman JM, Jassal SV, Oliver MJ, Na Y, Perl J. The impact of transfer from hemodialysis on peritoneal dialysis technique survival. Perit Dial Int. 2015 May-Jun;35(3):297-305. doi: 10.3747/pdi.2013.00147. Epub 2013 Dec 1.</citation>
    <PMID>24293665</PMID>
  </reference>
  <reference>
    <citation>Wong F. Management of ascites in cirrhosis. J Gastroenterol Hepatol. 2012 Jan;27(1):11-20. doi: 10.1111/j.1440-1746.2011.06925.x.</citation>
    <PMID>21916992</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>April 19, 2021</last_update_submitted>
  <last_update_submitted_qc>April 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Manitoba</investigator_affiliation>
    <investigator_full_name>Dr. Paul Komenda</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Liver Cirrhosis</keyword>
  <keyword>Refractory ascites</keyword>
  <keyword>PD catheter</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
    <mesh_term>Ascites</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02975726
org study id: B2014:066
nct id: NCT02975726
lead sponsor: 
has dmc: Yes
One complication of liver disease is the buildup of fluid within the belly. This is known as
      ascites. Patients who have ascites have a decreased appetite, pain, nausea and shortness of
      breath. Ascites is typically treated with medications, however when that does not work,
      patients need a procedure where a needle is inserted in the belly every few weeks to drain
      the excess fluid. About 2 in 5 patients with ascites from liver failure can get kidney
      disease from their worsening liver function or from the drainage of fluid with needles. Once
      patients have both advanced liver disease and kidney disease, their chance of dying largely
      increases.

      The present study will be the first of its kind to study a new technique to treat ascites.
      Investigators are planning to place a tube in a patient's belly to drain the excessive
      amounts of fluid. This technique is similar to how one type of dialysis is done to treat
      patients with kidney failure. This study is set as a pilot investigation in order to
      determine the feasibility of doing a larger, randomized clinical trial investigating the use
      of this novel technique. Importantly, advanced liver disease patients are at high risk to
      develop kidney disease, and therefore are an important group to focus on. Investigators
      believe that this technique will prevent or slow the development of kidney disease in liver
      failure patients, and improve their quality of life, far more than the current available
      treatments.
Refractory ascites is when fluid recurrently accumulates in the peritoneal cavity, as an end
      result of multiple mechanisms, including liver cirrhosis, peritoneal infiltration by tumor,
      portal hypertension, lymphangitic carcinomatosis, congestive heart failure, or lymphatic
      obstruction. It is associated with increased mortality and morbidity, including complications
      of abdominal wall hernias, spontaneous bacterial peritonitis, kidney dysfunction, and pleural
      effusions. The development of ascites also leads to multiple symptoms including anorexia,
      early satiety, nausea and vomiting, shortness of breath, and limited mobility.

      The management of ascites associated with liver dysfunction usually follows a stepwise
      escalation in treatments. The initial management typically involves sodium restriction and
      diuretic therapy up to a daily maximum of 160 mg of furosemide and 400 mg of spironolactone.
      When ascites no longer can be controlled by these measures, one option is to decrease portal
      hypertension, a main pathogenic factor in ascites development, by undergoing a procedure
      called transjugular intrahepatic portosystemic shunt (TIPS). This procedure requires certain
      patient criteria to be fulfilled and is associated with complications and increased risk of
      hepatic encephalopathy, and therefore is confined to a small subgroup of patients with
      ascites. Consequently, abdominal large volume paracentesis (LVP) is the treatment of choice
      in many patients. This procedure involves insertion of a needle into the peritoneal cavity
      where ascites accumulates, then attaching the needle to a collection system that drains the
      ascites by gravity. The definitive treatment for ascites in patients with cirrhosis is a
      liver transplant, but due to limited supply of organs, and contraindications to
      transplantation, patients often undergo repeated LVP while waiting on the wait list or until
      death. Paracentesis is associated with risks including post paracentesis circulatory
      dysfunction leading to hyponatremia, kidney dysfunction, viscus puncture, and peritonitis. It
      also is a costly, resource intense, and at times an uncomfortable treatment for patients due
      to the procedure itself and the need for repeated treatments.

      A potential alternative to LVP is the placement of an intraperitoneal catheter, in the same
      manner that a peritoneal dialysis (PD) catheter, to drain ascites. The procedure has a high
      technical insertion success rate with minimal complications and is routinely done at the
      bedside by nephrologist under local anesthesia. PD catheter placement for ascites drainage
      has many potential advantages, including the ability for it to be done at home by the patient
      and avoid visits to clinics or hospitals; the frequency of drainage can be timed to patient
      symptoms, and perhaps have less complication rates than LVP. However, the efficacy and safety
      of this approach in decompensated cirrhosis when compared to periodic LVP (current standard
      of care) has not been tested in a randomized trial. Investigators propose a single center,
      multi-site randomized control trial comparing bedside PD catheter placement versus usual
      standard of serial LVP for treatment of refractory ascites. The primary outcomes will be
      improvement of 10 points in the physical component score (PCS) of the Short Form-36 (SF-36)
      at two months. Investigators plan to randomize 50 patients (25 per arm) based on a power
      calculation to achieve an 10 point improvement in the PCS-SF-36 (SE = 5). Secondary outcomes
      will include incidence of mechanical and infectious complications, emergency department
      utilization, hospitalization and mortality, all other domains of the SF-36, Euroquol-5D
      (EQ-5D), the Newcastle Patient Reported Ascites Measure and overall health care costs.

      Primary Hypothesis: Drainage of ascites associated with liver failure via PD catheter is
      superior to serial LVP in improving the physical component of quality of life as measured by
      SF-36.

      This trial will be pivotal in possibly changing the standard of care for the management of
      refractory ascites from cirrhosis. If the primary hypothesis is confirmed, investigators will
      design and conduct subsequent trials to address potential morbidity and mortality benefits
      associated with this technique for ascites management.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in the physical component of Quality of Life
time frame: 2 months post intervention
description: Change in the physical component summary score of the SF 36 questionnaire.
measure: Catheter Insertion Technical Success Rate
time frame: Day of insertion of PD catheter
description: Technical success rate of tunneled PD catheters: Defined as successful positioning of the catheter in the intraperitoneal space with initial drainage of ascites
measure: PD Catheter Survival
time frame: Number of days between catheter insertion and possible complication, up to 6 months
description: Defined as days from insertion to date of a PD catheter related complication if they occur, assessed during the study timeframe.
measure: PD Catheter Related Complications Frequency
time frame: through study completion, up to 6 months
description: The number of participants with following complications: 1) Infection at the exit site or tunnel (as defined by the International Society of peritoneal Dialysis 2010 guidelines). 2) Peritonitis 3) intra-luminal/extra-luminal obstruction 4) catheter mal positioning (migration, omental wrapping) 5) Catheter leakage
measure: Large Volume Paracentesis Complications Frequency
time frame: through study completion, up to 6 months
description: The number of participants with following complications: 1) Peritonitis 2) leakage at puncture site 3) visceral puncture
measure: Participant Self-Reported Health Status
time frame: 0,2,4 and 6 months
description: Measured by the number of points as a result of participants' answers to SF-36 questionnaire
measure: Participant Health State Description and Evaluation
time frame: 0,2,4 and 6 months
description: Measured by the number of points as a result of participants' answers to EQ-5D questionnaire
measure: The Impact of Ascites on Health Related Quality of Life
time frame: 0,2,4 and 6 months
description: Measured by the number of points as a result of participants' answers to Newcastle Patient Reported Ascites Measure questionnaire
measure: Renal Dysfunction Assessment
time frame: Monthly, up to 6 months
description: Measured by blood work: serum creatinine, serum sodium, potassium, chloride, bicarbonate, urea, glucose, eGFR (estimated glomerular filtration rate).
measure: Renal Function Assessment
time frame: at 0 and 6 months
description: Measured by 24 hour urine collection: creatinine clearance, urine volume and urine sodium.
measure: Serum Albumin and PD Fluid Albumin Assesment
time frame: At 0, 2, and 6 months
description: PD catheter arm: Assessment of serum albumin and measurement of albumin in PD fluid at 0, 2, and 6 months
measure: Patient Heart Rate
time frame: At regular clinic appointments, through study completion, up to 6 months
description: Patient heart rate taken as part of regular physical assessment
measure: Patient Blood Pressure
time frame: At regular clinic appointments, through study completion, up to 6 months
description: Patient blood pressure taken as part of regular physical assessment
measure: Patient Weight
time frame: At regular clinic appointments, through study completion, up to 6 months
description: Patient weight taken as part of regular physical assessment
measure: Hospital Visits
time frame: through study completion, up to 6 months
description: The number of hospital admissions or emergency department visits from complications related to cirrhosis (encephalopathy, gastrointestinal bleed) or peritonitis.
measure: Total Health Care Costs
time frame: through study completion, up to 6 months
description: Direct health care costs will be estimated for both groups of patients taking a health care payor perspective.
measure: Cost Effectiveness
time frame: through study completion, up to 6 months
description: A decision analysis, Markov model will be constructed between the two intervention arms with outcomes expressed as cost per quality adjusted live year (cost per QALY) and expressed as incremental cost effectiveness ratios (ICER's).
arm group label: Peritoneal Dialysis Catheter Insertion
arm group type: Experimental
description: Catheters will be inserted at the bedside in a special procedure room.Argyle PD catheter kits will be used:2 cuffed curled catheters at 57cm or 62cm lengths. At time of PD catheter insertion,most patients will be drained of 5-10L of ascites or more to decrease the chance of catheter leaks.The volume removed will be at sole discretion of physician doing the procedure.Patients will be administered 25% Human Serum Albumin injection: 100cc after the 5-10L drainage,and 200cc if 10-15L is removed.Patients will undergo an initial drain and training with a specialized nurse.Patients in this arm will be instructed to drain a maximum of 2L per day after the initial drain.Monthly bloodwork will be performed.
arm group label: Large Volume Paracentesis
arm group type: Active Comparator
description: Patients in this arm of the study will continue their usual practice of LVP as required. They will continue to undergo their LVP procedures through their regular means.Monthly bloodwork will be performed.
intervention type: Device
intervention name: Peritoneal Dialysis Catheter
description: Peritoneal dialysis catheter insertion in order to drain access fluid within the belly for patients with liver cirrhosis and refractory ascites.
arm group label: Peritoneal Dialysis Catheter Insertion
intervention type: Procedure
intervention name: Large Volume Paracentesis
description: Insertion of a needle into the peritoneal cavity where ascites accumulates, then attaching the needle to a collection system that drains the ascites by gravity. This procedure is part of the standard care for the treatment of refractory ascites.
arm group label: Large Volume Paracentesis
intervention type: Biological
intervention name: 25% Human Serum Albumin injection
description: Patients will be given Human Serum Albumin after the initial drain of ascites fluid: 100cc for 5-10L drainage, 200cc for 10-15L drainage.
arm group label: Peritoneal Dialysis Catheter Insertion
intervention type: Procedure
intervention name: Bloodwork
description: Monthly bloodwork will be done as part of usual standard of care.
arm group label: Large Volume Paracentesis
arm group label: Peritoneal Dialysis Catheter Insertion
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paul Komenda, MD
role: Principal Investigator
affiliation: University of Manitoba
facility: 
country: Canada
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PMID: 21735084
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PMID: 21916992
responsible party type: Principal Investigator
investigator affiliation: University of Manitoba
investigator full name: Dr. Paul Komenda
investigator title: Associate Professor
mesh term: Liver Cirrhosis
mesh term: Fibrosis
mesh term: Ascites
sharing ipd: No