<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/NCT03829488</url>
  </required_header>
  <id_info>
    <org_study_id>15.02</org_study_id>
    <secondary_id>ACTRN12617000358347</secondary_id>
    <nct_id>NCT03829488</nct_id>
  </id_info>
  <brief_title>Better Evidence for Selecting Transplant Fluids</brief_title>
  <acronym>BEST-Fluids</acronym>
  <official_title>An Investigator-initiated, Pragmatic, Registry-based, Multi-centre, Double-blind, Randomised Controlled Trial Evaluating the Effect of Plasmalyte Versus 0.9% Saline on Early Kidney Transplant Function in Deceased Donor Kidney Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Queensland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Australian Government Department of Health and Ageing</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Health Research Council, New Zealand</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Baxter Healthcare Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Queensland</source>
  <oversight_info>
    <has_dmc>Yes</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>
      End-stage kidney disease (ESKD) is a significant, expensive health problem. Kidney&#xD;
      transplantation improves survival, quality of life, and is much cheaper than dialysis&#xD;
      treatment for ESKD. However sometimes kidney transplants from a deceased donor function&#xD;
      poorly after surgery, and a period of continued dialysis is needed, a condition known as&#xD;
      delayed graft function (DGF). In addition to complicating recovery, DGF can adversely affect&#xD;
      long-term kidney function and the health of the recipient.&#xD;
&#xD;
      Intravenous fluids given during and after transplantation (usually 0.9% sodium chloride or&#xD;
      saline) are critical to preserve kidney transplant function, but there is evidence that 0.9%&#xD;
      saline may not be the safest fluid to use due to its high chloride content.&#xD;
&#xD;
      BEST Fluids is a randomised controlled trial that aims to find out whether using a balanced&#xD;
      low-chloride solution - Plasma-Lyte 148® - as an alternative to normal saline in deceased&#xD;
      donor kidney transplantation, will improve kidney transplant function, reduce the impact of&#xD;
      DGF, and improve long-term outcomes for patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      End-stage kidney disease is a significant public health problem worldwide, and its treatment&#xD;
      imposes a high healthcare burden and cost. Kidney transplantation is considered the best&#xD;
      treatment for ESKD, offering improved survival and quality of life at significantly lower&#xD;
      cost that dialysis. However, many kidney transplants fail prematurely due in part due to&#xD;
      injury sustained at the time of transplantation. Delayed graft function (DGF), i.e. the&#xD;
      requirement for dialysis early after transplantation, affects approximately 30% of deceased&#xD;
      donor kidney transplants, and increases the risk of graft failure and mortality.&#xD;
&#xD;
      Intravenous fluids are a critical, albeit inexpensive, aspect of care that impacts early&#xD;
      transplant function with normal (0.9%) saline the current standard care at most centres.&#xD;
      However, normal saline may in fact be harmful in the setting of kidney transplantation due to&#xD;
      its high chloride content relative to plasma, causing metabolic acidosis, acute kidney injury&#xD;
      and thus potentially increasing the risk of DGF. Utilising a balanced low-chloride&#xD;
      crystalloid solution such as Plasma-Lyte 148® (Plasmalyte) as an alternative to 0.9% saline&#xD;
      may therefore improve outcomes after kidney transplantation.&#xD;
&#xD;
      The BEST-Fluids study is an investigator-initiated, pragmatic, registry-based, multi-centre,&#xD;
      double -blind randomised, controlled trial. The primary objective of the study is to evaluate&#xD;
      the effect in deceased donor kidney transplant recipients of intravenous therapy with&#xD;
      Plasmalyte versus 0.9% saline, commencing pre-operatively and continuing until intravenous&#xD;
      fluids are no longer required or 48 hours post-transplant (whichever is earliest), on DGF,&#xD;
      defined as the requirement for dialysis in the first seven days post-transplant.&#xD;
&#xD;
      Patients admitted for a deceased donor kidney transplant at participating centres will be&#xD;
      invited to participate in the study prior to transplant surgery. Following informed consent,&#xD;
      participants will be randomised to receive either blinded Plasmalyte or blinded 0.9% saline&#xD;
      for all intravenous fluid therapy purposes until 48 hours post-transplant. The volume and&#xD;
      rate of fluid therapy will be determined by treating clinicians; all other treatments will be&#xD;
      as per local standard of care. Participants will be enrolled, randomised and followed up&#xD;
      using ANZDATA, the Australia &amp; New Zealand Dialysis &amp; Transplant Registry.&#xD;
&#xD;
      The trial was prospectively registered with Australia New Zealand Clinical Trials Registry&#xD;
      (ANZCTR) on 08/03/2017 (ACTRN12617000358347).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 26, 2018</start_date>
  <completion_date type="Actual">May 3, 2022</completion_date>
  <primary_completion_date type="Actual">July 29, 2021</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of participants with Delayed Graft Function</measure>
    <time_frame>7 Days</time_frame>
    <description>Delayed Graft Function defined as receiving treatment with any form of dialysis in the first seven days after transplant</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Early Kidney Transplant Function</measure>
    <time_frame>a. Duration of Delayed Graft Function - 12 Weeks; b. Rate of recovery of kidney transplant graft function - 2 Days</time_frame>
    <description>Early Kidney Transplant Function, a ranked composite of&#xD;
Duration of Delayed Graft Function Description: Participants who require dialysis within seven days post-transplant, the time from transplant to the final dialysis treatment in days (up to 84 days/12 weeks) will be ranked from best to worst (longer times are worse).&#xD;
Rate of recovery of kidney transplant graft function Description: for participants who do not require dialysis, graft function assessed using the creatinine reduction ratio on post-transplant day two (CRR2) will be ranked from best to worst (smaller reductions are worse).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of dialysis sessions</measure>
    <time_frame>First 28 days post-transplant</time_frame>
    <description>The number of dialysis sessions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total duration of dialysis</measure>
    <time_frame>12 Weeks</time_frame>
    <description>The total duration of dialysis in days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Creatinine reduction ratio from day 1 to day 2 post-transplant</measure>
    <time_frame>Day 1 to Day 2 post-transplant</time_frame>
    <description>Creatinine reduction ratio from day one to day two measured using serum assay, for those who do not require dialysis within the first 7 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in serum creatinine of greater than or equal to 10%</measure>
    <time_frame>First 7 days post-transplant</time_frame>
    <description>The proportion of subjects with a reduction in serum creatinine of greater than or equal to 10% on three consecutive days in the first 7 days post-transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum creatinine trends over 52 weeks</measure>
    <time_frame>12 months</time_frame>
    <description>Serum creatinine trends measured over 52 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of serum potassium greater than or equal to 5.5 mmol/L</measure>
    <time_frame>First 48 hours post-transplant</time_frame>
    <description>Serum potassium greater than or equal to 5.5 mmol/L measured by serum assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak potassium level</measure>
    <time_frame>First 48 hours post-transplant</time_frame>
    <description>Peak potassium level, measured by serum assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment for hyperkalaemia</measure>
    <time_frame>First 48 hours post-transplant</time_frame>
    <description>Treatment for hyperkalaemia with dialysis, Ca2+-gluconate, insulin, beta-agonists, sodium bicarbonate or ion exchange resins in the first 48 hours post-transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of significant fluid overload</measure>
    <time_frame>Baseline to day 2</time_frame>
    <description>Incidence of significant fluid overload defined as &gt;5% weight gain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aggregate urine output</measure>
    <time_frame>Until day 2 post-transplant</time_frame>
    <description>Aggregate urine output until day 2 post-transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Requirement for inotropic support (use of vasopressors or other drugs to maintain adequate blood pressure)</measure>
    <time_frame>Intra- and post-operatively to Day 2</time_frame>
    <description>Requirement for inotropic support both intra- and post-operatively to Day 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of acute rejection episodes</measure>
    <time_frame>12 months</time_frame>
    <description>Number of acute rejection episodes in the first 52 weeks as reported by ANZDATA routine data capture and as assessed by treating physicians</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of renal transplant biopsies</measure>
    <time_frame>First 28 days post-transplant</time_frame>
    <description>Number of renal transplant biopsies performed in the first 28 days post-transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death from all causes</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Death from all causes up to 52 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft survival</measure>
    <time_frame>12 months</time_frame>
    <description>Graft survival and death-censored graft survival as reported by ANZDATA and assessed by treating physician</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft function</measure>
    <time_frame>4, 12, 26 and 52 weeks</time_frame>
    <description>Graft function (estimated glomerular filtration rate; eGFR) at 4, 12, 26 and 52 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life</measure>
    <time_frame>Baseline, day 7, day 28, week 12, week 26, and week 52</time_frame>
    <description>Health-related quality of life measured using EuroQol EQ-5D-5L for adults, and EQ-5D-Y in children under 18 years. EQ-5D has descriptive and visual analogue scale (VAS). Descriptive system consists of five dimensions mobility, self-care, usual activities, pain/discomfort and anxiety/depression. VAS records patient's self-rated health on vertical visual analogue scale with endpoints best to worst health with 0 being worst and 100 being best health.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>12 months</time_frame>
    <description>Length of hospital stay over 12 months using linked data state and country based health data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Healthcare resource use</measure>
    <time_frame>12 months</time_frame>
    <description>Healthcare resource use over 12 months using linked data state and country based health data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost-effectiveness</measure>
    <time_frame>12 months</time_frame>
    <description>Cost-effectiveness over 12 months using linked data state and country based health data</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">808</enrollment>
  <condition>End Stage Kidney Disease</condition>
  <condition>Delayed Graft Function</condition>
  <condition>Kidney Transplant; Complications</condition>
  <arm_group>
    <arm_group_label>Plasma-Lyte 148 (approx. pH 7.4) IV Infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Plasma-Lyte 148 (approx. pH 7.4) IV Infusion intravenous fluid therapy will be used for all maintenance, replacement and resuscitation purposes from randomization onwards until 48 hours post-transplant, or until fluid therapy is no longer required, if earlier.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.9% SODIUM CHLORIDE 9g/L injection BP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>0.9% saline intravenous fluid therapy will be used for all maintenance, replacement and resuscitation purposes from randomization onwards until 48 hours post-transplant, or until fluid therapy is no longer required, if earlier.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Plasma-Lyte 148 (approx. pH 7.4) IV Infusion</intervention_name>
    <description>Plasma-Lyte 148 (approx. pH 7.4) IV Infusion is a sterile, clear, non-pyrogenic isotonic solution and when administered intravenously is a source of water, electrolytes and calories. Plasma-Lyte 148 intravenous infusion is indicated as a source of water &amp; electrolytes or as an alkalinising agent.</description>
    <arm_group_label>Plasma-Lyte 148 (approx. pH 7.4) IV Infusion</arm_group_label>
    <other_name>Plasma-Lyte 148®</other_name>
    <other_name>Plasmalyte</other_name>
    <other_name>Balanced crystalloid solution</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.9% SODIUM CHLORIDE 9g/L injection BP</intervention_name>
    <description>Sodium chloride (0.9% saline) infusion is a sterile, non-pyrogenic solution of sodium chloride in Water for Injections. The concentration of sodium chloride is 154mmol/L. Sodium chloride (0.9%) intravenous infusion is indicated for extra-cellular fluid replacement and in the management of metabolic alkalosis in the presence of fluid loss, and for restoring or maintaining the concentration of sodium and chloride ions.</description>
    <arm_group_label>0.9% SODIUM CHLORIDE 9g/L injection BP</arm_group_label>
    <other_name>0.9% saline</other_name>
    <other_name>Normal saline</other_name>
    <other_name>Isotonic saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult or child with End-Stage Kidney Disease, of any cause, on maintenance dialysis,&#xD;
             or who has pre-dialysis stage 5 chronic kidney disease with an estimated Glomerular&#xD;
             Filtration Rate of &lt;15 mL/min/1.73m2, AND&#xD;
&#xD;
          2. Planned deceased donor kidney transplant from a brain-death (DBD) or circulatory-death&#xD;
             (DCD) organ donor within 24 hours, AND&#xD;
&#xD;
          3. Written informed consent, or consent given by their parent or guardian (if age &lt;18),&#xD;
             or other authorised person&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Planned live donor kidney transplant (except where this is cancelled in favour or&#xD;
             transplantation from a deceased donor)&#xD;
&#xD;
          2. Planned multi-organ transplant (dual or en-bloc kidney transplants are not excluded)&#xD;
&#xD;
          3. Children of weight &lt;20 kg, or a child that the treating physician believes should not&#xD;
             be included in a study of blinded fluids due to their small body size&#xD;
&#xD;
          4. Known hypersensitivity to the trial fluid preparations or packaging&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Collins, MBChB,FRACP,PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Auckland District Health Board &amp; The University of Auckland</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steven Chadban, BMed(hons),FRACP,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sydney Local Health District &amp; The University of Sydney</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sydney Children's Hospital</name>
      <address>
        <city>Randwick</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Prince Alfred Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital at Westmead</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westmead Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queensland Children's Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's Hospital (Melbourne) Ltd</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Health</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Children's Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Medical Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fiona Stanley Hospital</name>
      <address>
        <city>Murdoch</city>
        <state>Western Australia</state>
        <zip>6150</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sir Charles Gairdner Hospital</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland City Hospital</name>
      <address>
        <city>Auckland</city>
        <zip>1142</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Starship Children's Hospital</name>
      <address>
        <city>Auckland</city>
        <zip>1142</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christchurch Hospital</name>
      <address>
        <city>Christchurch</city>
        <zip>8011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellington Hospital</name>
      <address>
        <city>Wellington</city>
        <zip>6021</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>New Zealand</country>
  </location_countries>
  <link>
    <url>http://aktn.org.au/best-fluids</url>
    <description>Australasian Kidney Trials Network Website</description>
  </link>
  <link>
    <url>https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-020-04359-2</url>
    <description>Study protocol paper</description>
  </link>
  <link>
    <url>https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05989-w#change-history</url>
    <description>Statistical Analysis Plan paper</description>
  </link>
  <link>
    <url>https://journals.lww.com/transplantationdirect/Fulltext/2022/12000/Baseline_Characteristics_and_Representativeness_of.5.aspx?context=LatestArticles</url>
    <description>Baseline characteristics and representativeness paper</description>
  </link>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>January 21, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>December 12, 2022</last_update_submitted>
  <last_update_submitted_qc>December 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Kidney Failure, Chronic</mesh_term>
    <mesh_term>Delayed Graft Function</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Plasma-lyte 148</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Yes Individual participant data that underlie the results reported in the primary publication, after de-identification (text, tables, figures and appendices) will be available for individual participant data meta-analysis.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Beginning 2 years and ending 5 years following main publication. Proposals may be submitted up to 5 years following article publication. After 5 years, the data will be available in our University's data warehouse but without investigator support other than deposited metadata.</ipd_time_frame>
    <ipd_access_criteria>An independent review board will assess proposals based on the following criteria: sound science, benefit-risk balancing and research team expertise.</ipd_access_criteria>
  </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/NCT03829488
org study id: 15.02
secondary id: ACTRN12617000358347
nct id: NCT03829488
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
End-stage kidney disease (ESKD) is a significant, expensive health problem. Kidney
      transplantation improves survival, quality of life, and is much cheaper than dialysis
      treatment for ESKD. However sometimes kidney transplants from a deceased donor function
      poorly after surgery, and a period of continued dialysis is needed, a condition known as
      delayed graft function (DGF). In addition to complicating recovery, DGF can adversely affect
      long-term kidney function and the health of the recipient.

      Intravenous fluids given during and after transplantation (usually 0.9% sodium chloride or
      saline) are critical to preserve kidney transplant function, but there is evidence that 0.9%
      saline may not be the safest fluid to use due to its high chloride content.

      BEST Fluids is a randomised controlled trial that aims to find out whether using a balanced
      low-chloride solution - Plasma-Lyte 148® - as an alternative to normal saline in deceased
      donor kidney transplantation, will improve kidney transplant function, reduce the impact of
      DGF, and improve long-term outcomes for patients.
End-stage kidney disease is a significant public health problem worldwide, and its treatment
      imposes a high healthcare burden and cost. Kidney transplantation is considered the best
      treatment for ESKD, offering improved survival and quality of life at significantly lower
      cost that dialysis. However, many kidney transplants fail prematurely due in part due to
      injury sustained at the time of transplantation. Delayed graft function (DGF), i.e. the
      requirement for dialysis early after transplantation, affects approximately 30% of deceased
      donor kidney transplants, and increases the risk of graft failure and mortality.

      Intravenous fluids are a critical, albeit inexpensive, aspect of care that impacts early
      transplant function with normal (0.9%) saline the current standard care at most centres.
      However, normal saline may in fact be harmful in the setting of kidney transplantation due to
      its high chloride content relative to plasma, causing metabolic acidosis, acute kidney injury
      and thus potentially increasing the risk of DGF. Utilising a balanced low-chloride
      crystalloid solution such as Plasma-Lyte 148® (Plasmalyte) as an alternative to 0.9% saline
      may therefore improve outcomes after kidney transplantation.

      The BEST-Fluids study is an investigator-initiated, pragmatic, registry-based, multi-centre,
      double -blind randomised, controlled trial. The primary objective of the study is to evaluate
      the effect in deceased donor kidney transplant recipients of intravenous therapy with
      Plasmalyte versus 0.9% saline, commencing pre-operatively and continuing until intravenous
      fluids are no longer required or 48 hours post-transplant (whichever is earliest), on DGF,
      defined as the requirement for dialysis in the first seven days post-transplant.

      Patients admitted for a deceased donor kidney transplant at participating centres will be
      invited to participate in the study prior to transplant surgery. Following informed consent,
      participants will be randomised to receive either blinded Plasmalyte or blinded 0.9% saline
      for all intravenous fluid therapy purposes until 48 hours post-transplant. The volume and
      rate of fluid therapy will be determined by treating clinicians; all other treatments will be
      as per local standard of care. Participants will be enrolled, randomised and followed up
      using ANZDATA, the Australia & New Zealand Dialysis & Transplant Registry.

      The trial was prospectively registered with Australia New Zealand Clinical Trials Registry
      (ANZCTR) on 08/03/2017 (ACTRN12617000358347).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The proportion of participants with Delayed Graft Function
time frame: 7 Days
description: Delayed Graft Function defined as receiving treatment with any form of dialysis in the first seven days after transplant
measure: Early Kidney Transplant Function
time frame: a. Duration of Delayed Graft Function - 12 Weeks; b. Rate of recovery of kidney transplant graft function - 2 Days
description: Early Kidney Transplant Function, a ranked composite of
Duration of Delayed Graft Function Description: Participants who require dialysis within seven days post-transplant, the time from transplant to the final dialysis treatment in days (up to 84 days/12 weeks) will be ranked from best to worst (longer times are worse).
Rate of recovery of kidney transplant graft function Description: for participants who do not require dialysis, graft function assessed using the creatinine reduction ratio on post-transplant day two (CRR2) will be ranked from best to worst (smaller reductions are worse).
measure: Number of dialysis sessions
time frame: First 28 days post-transplant
description: The number of dialysis sessions
measure: Total duration of dialysis
time frame: 12 Weeks
description: The total duration of dialysis in days
measure: Creatinine reduction ratio from day 1 to day 2 post-transplant
time frame: Day 1 to Day 2 post-transplant
description: Creatinine reduction ratio from day one to day two measured using serum assay, for those who do not require dialysis within the first 7 days
measure: Reduction in serum creatinine of greater than or equal to 10%
time frame: First 7 days post-transplant
description: The proportion of subjects with a reduction in serum creatinine of greater than or equal to 10% on three consecutive days in the first 7 days post-transplant
measure: Serum creatinine trends over 52 weeks
time frame: 12 months
description: Serum creatinine trends measured over 52 weeks
measure: Incidence of serum potassium greater than or equal to 5.5 mmol/L
time frame: First 48 hours post-transplant
description: Serum potassium greater than or equal to 5.5 mmol/L measured by serum assay
measure: Peak potassium level
time frame: First 48 hours post-transplant
description: Peak potassium level, measured by serum assay
measure: Treatment for hyperkalaemia
time frame: First 48 hours post-transplant
description: Treatment for hyperkalaemia with dialysis, Ca2+-gluconate, insulin, beta-agonists, sodium bicarbonate or ion exchange resins in the first 48 hours post-transplant
measure: Incidence of significant fluid overload
time frame: Baseline to day 2
description: Incidence of significant fluid overload defined as >5% weight gain
measure: Aggregate urine output
time frame: Until day 2 post-transplant
description: Aggregate urine output until day 2 post-transplant
measure: Requirement for inotropic support (use of vasopressors or other drugs to maintain adequate blood pressure)
time frame: Intra- and post-operatively to Day 2
description: Requirement for inotropic support both intra- and post-operatively to Day 2
measure: Number of acute rejection episodes
time frame: 12 months
description: Number of acute rejection episodes in the first 52 weeks as reported by ANZDATA routine data capture and as assessed by treating physicians
measure: Number of renal transplant biopsies
time frame: First 28 days post-transplant
description: Number of renal transplant biopsies performed in the first 28 days post-transplant
measure: Death from all causes
time frame: Up to 52 weeks
description: Death from all causes up to 52 weeks
measure: Graft survival
time frame: 12 months
description: Graft survival and death-censored graft survival as reported by ANZDATA and assessed by treating physician
measure: Graft function
time frame: 4, 12, 26 and 52 weeks
description: Graft function (estimated glomerular filtration rate; eGFR) at 4, 12, 26 and 52 weeks
measure: Health-related quality of life
time frame: Baseline, day 7, day 28, week 12, week 26, and week 52
description: Health-related quality of life measured using EuroQol EQ-5D-5L for adults, and EQ-5D-Y in children under 18 years. EQ-5D has descriptive and visual analogue scale (VAS). Descriptive system consists of five dimensions mobility, self-care, usual activities, pain/discomfort and anxiety/depression. VAS records patient's self-rated health on vertical visual analogue scale with endpoints best to worst health with 0 being worst and 100 being best health.
measure: Length of hospital stay
time frame: 12 months
description: Length of hospital stay over 12 months using linked data state and country based health data
measure: Healthcare resource use
time frame: 12 months
description: Healthcare resource use over 12 months using linked data state and country based health data
measure: Cost-effectiveness
time frame: 12 months
description: Cost-effectiveness over 12 months using linked data state and country based health data
arm group label: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion
arm group type: Experimental
description: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion intravenous fluid therapy will be used for all maintenance, replacement and resuscitation purposes from randomization onwards until 48 hours post-transplant, or until fluid therapy is no longer required, if earlier.
arm group label: 0.9% SODIUM CHLORIDE 9g/L injection BP
arm group type: Active Comparator
description: 0.9% saline intravenous fluid therapy will be used for all maintenance, replacement and resuscitation purposes from randomization onwards until 48 hours post-transplant, or until fluid therapy is no longer required, if earlier.
intervention type: Drug
intervention name: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion
description: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion is a sterile, clear, non-pyrogenic isotonic solution and when administered intravenously is a source of water, electrolytes and calories. Plasma-Lyte 148 intravenous infusion is indicated as a source of water & electrolytes or as an alkalinising agent.
arm group label: Plasma-Lyte 148 (approx. pH 7.4) IV Infusion
other name: Plasma-Lyte 148®
other name: Plasmalyte
other name: Balanced crystalloid solution
intervention type: Drug
intervention name: 0.9% SODIUM CHLORIDE 9g/L injection BP
description: Sodium chloride (0.9% saline) infusion is a sterile, non-pyrogenic solution of sodium chloride in Water for Injections. The concentration of sodium chloride is 154mmol/L. Sodium chloride (0.9%) intravenous infusion is indicated for extra-cellular fluid replacement and in the management of metabolic alkalosis in the presence of fluid loss, and for restoring or maintaining the concentration of sodium and chloride ions.
arm group label: 0.9% SODIUM CHLORIDE 9g/L injection BP
other name: 0.9% saline
other name: Normal saline
other name: Isotonic saline
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Michael Collins, MBChB,FRACP,PhD
role: Study Chair
affiliation: Auckland District Health Board & The University of Auckland
last name: Steven Chadban, BMed(hons),FRACP,PhD
role: Principal Investigator
affiliation: Sydney Local Health District & The University of Sydney
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country: Australia
country: New Zealand
url: http://aktn.org.au/best-fluids
description: Australasian Kidney Trials Network Website
url: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-020-04359-2
description: Study protocol paper
url: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05989-w#change-history
description: Statistical Analysis Plan paper
url: https://journals.lww.com/transplantationdirect/Fulltext/2022/12000/Baseline_Characteristics_and_Representativeness_of.5.aspx?context=LatestArticles
description: Baseline characteristics and representativeness paper
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Kidney Failure, Chronic
mesh term: Delayed Graft Function
mesh term: Plasma-lyte 148
sharing ipd: Yes
ipd description: Yes Individual participant data that underlie the results reported in the primary publication, after de-identification (text, tables, figures and appendices) will be available for individual participant data meta-analysis.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Beginning 2 years and ending 5 years following main publication. Proposals may be submitted up to 5 years following article publication. After 5 years, the data will be available in our University's data warehouse but without investigator support other than deposited metadata.
ipd access criteria: An independent review board will assess proposals based on the following criteria: sound science, benefit-risk balancing and research team expertise.