<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/NCT03251131</url>
  </required_header>
  <id_info>
    <org_study_id>HUS/1782/2017</org_study_id>
    <nct_id>NCT03251131</nct_id>
  </id_info>
  <brief_title>REVERSE-AKI Randomized Controlled Pilot Trial</brief_title>
  <acronym>REVERSE-AKI</acronym>
  <official_title>REstricted Fluid Therapy VERsus Standard trEatment in Acute Kidney Injury - REVERSE-AKI Randomized Controlled Pilot Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helsinki University Central Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Austin Hospital, Melbourne Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Ghent</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical University Innsbruck</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lausanne University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Helsinki University Central Hospital</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>
      Observational studies among patients with acute kidney injury (AKI) have shown an association&#xD;
      with fluid accumulation and increased mortality. Trials among other subgroups of critically&#xD;
      ill patients have demonstrated that restricting fluid input after the initial resuscitation&#xD;
      appears safe.&#xD;
&#xD;
      The objective if this study is to determine whether a fluid restrictive treatment regimen&#xD;
      will lead to a lower cumulative fluid balance at 72 hours from randomization in critically&#xD;
      ill patients with AKI and whether this approach is safe and feasible.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acute kidney injury (AKI) is common in the critically ill and associates with adverse&#xD;
      outcomes. Patients with AKI are frequently have low urine output and are at high risk of&#xD;
      developing fluid overload. Fluid overload has been associated with an increased risk for&#xD;
      mortality in such patients. Previous trials in critically ill patients found that a&#xD;
      'restrictive fluid therapy' after resuscitation was safe. Implementing a restrictive fluid&#xD;
      therapy approach in patients with AKI may also be of benefit. To date, however, no randomized&#xD;
      trial has been performed to evaluate the safety and feasibility of implementing a&#xD;
      'restrictive fluid therapy' approach compared to standard fluid therapy in patients with AKI.&#xD;
&#xD;
      In this pilot randomized controlled trial we will evaluate the implementation of a fluid&#xD;
      restrictive approach, compared to standard therapy, in adult critically ill patients with&#xD;
      acute kidney injury.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 8, 2017</start_date>
  <completion_date type="Actual">April 30, 2020</completion_date>
  <primary_completion_date type="Actual">January 31, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cumulative fluid balance</measure>
    <time_frame>72 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of acute kidney injury</measure>
    <time_frame>ICU discharge/14 days</time_frame>
    <description>Defined according to Kidney Disease: Improving Global Outcomes criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients requiring renal replacement therapy</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative fluid balance</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative fluid balance</measure>
    <time_frame>ICU discharge/ 7 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative dose of diuretics</measure>
    <time_frame>ICU discharge/ 7 days</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of patients with serious adverse events and reactions</measure>
    <time_frame>7 days</time_frame>
    <description>a Ventricular tachycardia/fibrillation b. New onset of atrial fibrillation requiring medication/defibrillation c. Ischemic events i. Acute myocardial infarction ii. Cerebral ischemia verified by CT or MRI scan.&#xD;
iii. Intestinal ischemia verified by endoscopy or open surgery.&#xD;
iv. Acute peripheral limb ischemia d. Radiologically diagnosed pulmonary edema e. Adverse events related to renal replacement therapy and diuretics use f. Frequency of hypokalaemia (serum K &lt;3.5mmol/L) g. Frequency of hypomagnesaemia (serum Mg &lt;0.8mmol/L) h. frequency of serum pH &gt;7.5 i. other</description>
  </other_outcome>
  <other_outcome>
    <measure>Mechanical ventilation free days alive</measure>
    <time_frame>14 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Vasopressor free days and alive</measure>
    <time_frame>14 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Renal replacement therapy free days and alive</measure>
    <time_frame>90 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Dialysis dependence</measure>
    <time_frame>90 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>90 days</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Acute Kidney Injury</condition>
  <condition>Critical Illness</condition>
  <arm_group>
    <arm_group_label>Restrictive fluid management</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Restrictive fluid management Targeting a negative or maximum 300ml positive daily fluid balance.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard therapy</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Randomized allocation of standard care at the clinician's discretion in accordance with current best practice.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Restrictive fluid management</intervention_name>
    <description>Daily fluid input is restricted to drugs and nutrition. Fluid boluses and blood products can be given if clinically indicated. Matching fluid output to fluid input whenever possible using diuretics if needed, and additionally, if clinically necessary and plausible, commencing renal replacement therapy. If renal replacement therapy is not deemed clinically desirable, acceptance of a less than targeted fluid balance.</description>
    <arm_group_label>Restrictive fluid management</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18-years or older and admitted to critical care with an arterial line in place&#xD;
&#xD;
          2. The patient has been in critical care for at least 12 hours but no more than 72 hours&#xD;
&#xD;
          3. The patient has AKI but is not receiving acute RRT:&#xD;
&#xD;
             For the purpose of the study AKI is defined the by the following criteria:&#xD;
&#xD;
               1. Increase in serum creatinine over 1.5-times above baseline without a decline of&#xD;
                  27umol/l or more from the last preceding measurement (at least 12 hours apart)&#xD;
                  AND/OR&#xD;
&#xD;
               2. Overall urine output less than 0.5ml/kg/h (or 6ml/kg) for the previous 12h (with&#xD;
                  urine catheter in place for the period)&#xD;
&#xD;
          4. The patient is judged by the treating clinician not to be intravascularly hypovolemic&#xD;
&#xD;
          5. The patient is likely to remain in critical care for 48 hours after randomization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Active bleeding necessitating transfusion&#xD;
&#xD;
          2. Maintenance fluid therapy is necessary due to diabetic ketoacidosis, non-ketotic coma,&#xD;
             severe burns or other clinical reason determined by the medical staff&#xD;
&#xD;
          3. Need for RRT due to intoxication of a dialyzable toxin&#xD;
&#xD;
          4. Commencement of RRT is expected in the next 6 hours&#xD;
&#xD;
          5. On chronic renal replacement therapy (maintenance dialysis or renal transplant)&#xD;
&#xD;
          6. Presence or a strong clinical suspicion of parenchymal AKI (for example&#xD;
             glomerulonephritis, vasculitis, acute interstitial nephritis), or post-renal&#xD;
             obstruction&#xD;
&#xD;
          7. Severe hyponatremia (Na &lt;125mmol/L) or hypernatremia (Na &gt;155mmol/L)&#xD;
&#xD;
          8. Need for extracorporeal membrane oxygenation or molecular absorbent recirculating&#xD;
             system (MARS-therapy)&#xD;
&#xD;
          9. Pregnant or lactating&#xD;
&#xD;
         10. Patients who are not to receive full active treatment&#xD;
&#xD;
         11. No baseline creatinine available&#xD;
&#xD;
         12. Lack of consent&#xD;
&#xD;
         13. The patient has been enrolled in another trial where co-enrollment is not feasible&#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>Suvi Vaara, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marlies Ostermann, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Critical Care and Nephrology, King's College London, Guy's and St Thomas Hospital, Foundation Hospital, London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Austin Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3048</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Canberra Hospital</name>
      <address>
        <city>Canberra</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ghent University Hospital</name>
      <address>
        <city>Ghent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helsinki University Hospital</name>
      <address>
        <city>Helsinki</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lausanne University Hospital</name>
      <address>
        <city>Lausanne</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's and St Thomas Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal London Hospital, Barts Health NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Finland</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Austria</country>
    <country>Germany</country>
  </removed_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>August 12, 2017</study_first_submitted>
  <study_first_submitted_qc>August 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>December 10, 2020</last_update_submitted>
  <last_update_submitted_qc>December 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Helsinki University Central Hospital</investigator_affiliation>
    <investigator_full_name>Suvi Vaara</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Kidney Injury</mesh_term>
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03251131
org study id: HUS/1782/2017
nct id: NCT03251131
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Observational studies among patients with acute kidney injury (AKI) have shown an association
      with fluid accumulation and increased mortality. Trials among other subgroups of critically
      ill patients have demonstrated that restricting fluid input after the initial resuscitation
      appears safe.

      The objective if this study is to determine whether a fluid restrictive treatment regimen
      will lead to a lower cumulative fluid balance at 72 hours from randomization in critically
      ill patients with AKI and whether this approach is safe and feasible.
Acute kidney injury (AKI) is common in the critically ill and associates with adverse
      outcomes. Patients with AKI are frequently have low urine output and are at high risk of
      developing fluid overload. Fluid overload has been associated with an increased risk for
      mortality in such patients. Previous trials in critically ill patients found that a
      'restrictive fluid therapy' after resuscitation was safe. Implementing a restrictive fluid
      therapy approach in patients with AKI may also be of benefit. To date, however, no randomized
      trial has been performed to evaluate the safety and feasibility of implementing a
      'restrictive fluid therapy' approach compared to standard fluid therapy in patients with AKI.

      In this pilot randomized controlled trial we will evaluate the implementation of a fluid
      restrictive approach, compared to standard therapy, in adult critically ill patients with
      acute kidney injury.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Cumulative fluid balance
time frame: 72 hours
measure: Duration of acute kidney injury
time frame: ICU discharge/14 days
description: Defined according to Kidney Disease: Improving Global Outcomes criteria
measure: Number of patients requiring renal replacement therapy
time frame: 14 days
measure: Cumulative fluid balance
time frame: 24 hours
measure: Cumulative fluid balance
time frame: ICU discharge/ 7 days
measure: Cumulative dose of diuretics
time frame: ICU discharge/ 7 days
measure: Number of patients with serious adverse events and reactions
time frame: 7 days
description: a Ventricular tachycardia/fibrillation b. New onset of atrial fibrillation requiring medication/defibrillation c. Ischemic events i. Acute myocardial infarction ii. Cerebral ischemia verified by CT or MRI scan.
iii. Intestinal ischemia verified by endoscopy or open surgery.
iv. Acute peripheral limb ischemia d. Radiologically diagnosed pulmonary edema e. Adverse events related to renal replacement therapy and diuretics use f. Frequency of hypokalaemia (serum K <3.5mmol/L) g. Frequency of hypomagnesaemia (serum Mg <0.8mmol/L) h. frequency of serum pH >7.5 i. other
measure: Mechanical ventilation free days alive
time frame: 14 days
measure: Vasopressor free days and alive
time frame: 14 days
measure: Renal replacement therapy free days and alive
time frame: 90 days
measure: Dialysis dependence
time frame: 90 days
measure: All-cause mortality
time frame: 90 days
arm group label: Restrictive fluid management
arm group type: Experimental
description: Restrictive fluid management Targeting a negative or maximum 300ml positive daily fluid balance.
arm group label: Standard therapy
arm group type: No Intervention
description: Randomized allocation of standard care at the clinician's discretion in accordance with current best practice.
intervention type: Other
intervention name: Restrictive fluid management
description: Daily fluid input is restricted to drugs and nutrition. Fluid boluses and blood products can be given if clinically indicated. Matching fluid output to fluid input whenever possible using diuretics if needed, and additionally, if clinically necessary and plausible, commencing renal replacement therapy. If renal replacement therapy is not deemed clinically desirable, acceptance of a less than targeted fluid balance.
arm group label: Restrictive fluid management
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Suvi Vaara, MD, PhD
role: Principal Investigator
affiliation: Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
last name: Marlies Ostermann, MD, PhD
role: Principal Investigator
affiliation: Department of Critical Care and Nephrology, King's College London, Guy's and St Thomas Hospital, Foundation Hospital, London
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Belgium
country: Finland
country: Switzerland
country: United Kingdom
country: Austria
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Helsinki University Central Hospital
investigator full name: Suvi Vaara
investigator title: MD, PhD
mesh term: Acute Kidney Injury
mesh term: Critical Illness