<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/NCT03836742</url>
  </required_header>
  <id_info>
    <org_study_id>NKBBN/539/2016-17</org_study_id>
    <nct_id>NCT03836742</nct_id>
  </id_info>
  <brief_title>HEmoFiltration With Citric Acid Anticoagulation</brief_title>
  <acronym>HEFCAA</acronym>
  <official_title>Evaluation of Safety and Efficacy of a Regional Anticoagulation Protocol for Continuous Renal Replacement Therapies.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Gdansk</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Gdansk</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prospective observational study of all consecutive cardio-vascular surgical patients treated&#xD;
      with post-dilution hemofiltration with regional citrate anticoagulation as first-choice&#xD;
      anticoagulation method. The filter life-span was assessed in the context of postoperative&#xD;
      cardiac surgical antithrombotic prophylaxis. Reasons for termination of hemofiltration&#xD;
      sessions were assessed. The second aim of this study was to assess the influence ACD-A based&#xD;
      anticoagulation protocol on acid-base and ion homeostasis in cardiac surgical patients with&#xD;
      acute renal failure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All consecutive cardio-vascular surgery patients treated with post-dilution hemofiltration&#xD;
      with regional citrate anticoagulation (HF RCA) from August 2015 through November 2017 were&#xD;
      included to prospective audit. Indication to hemofiltration treatment was based on clinical&#xD;
      assessment of patients renal function and clinical status by attending physician and&#xD;
      conformed conventional indications to renal replacement therapy (RRT) in intensive care unit&#xD;
      (ICU). Severe chronic liver disease or acute liver injury with INR &gt; 2 and refractory shock&#xD;
      with lactate increasing above 8 mmol/L were considered as contraindication to RCA.&#xD;
&#xD;
      Initially set blood flow was 5 times higher than filtrate flow, which makes filtration&#xD;
      fraction of 20%. To reduce the risk of metabolic alkalosis, ACD-A citrate solution was&#xD;
      proposed instead of most commonly used trisodium citrate solution, and relatively low target&#xD;
      citrate concentration (2.8 mmol/L) was adopted. In case of pH increase above 7.5 or&#xD;
      bicarbonate concentration above 40 mmol/L filtrate flow was decreased from initial 35&#xD;
      ml/kg/hour down to 25 ml/kg/hour which should reduce bicarbonate synthesis by 25%. If&#xD;
      metabolic alkalosis persisted, the second step involved reduction of blood flow from initial&#xD;
      5 times down to 4 times filtrate flow, which reduced citrate flow by the same factor.&#xD;
&#xD;
      In order to avoid hypomagnesemia resulting from magnesium binding to citrate, and its removal&#xD;
      with ultrafiltrate not balanced with magnesium content in replacement fluid, the original&#xD;
      protocol was modified by connecting magnesium sulfate solution 2g/50 ml 0.9% NaCl at the flow&#xD;
      1 mL/hour.&#xD;
&#xD;
      All sessions stopped due to patients death before 48 hours of HF treatment were excluded from&#xD;
      the analysis. Similarly, all cases where hemofiltration session was stopped before 48 hours&#xD;
      of treatment due to organizational reasons, recovery of renal function, change of therapy,&#xD;
      and when patients were treated with heparin infusion due to surgical indications were&#xD;
      excluded from further circuit survival analysis.&#xD;
&#xD;
      Blood gas parameters together with pH, bicarbonate concentration, Na, Cl, K, Ca, hemoglobin&#xD;
      concentration, hematocrit, lactate, and anion gap were analyzed every 6 hours. Post filter&#xD;
      ionized calcium concentration was not assessed. Serum phosphate, magnesium and total calcium&#xD;
      was assessed every 24 hours during hemofiltration treatment with RCA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 11, 2015</start_date>
  <completion_date type="Actual">December 31, 2017</completion_date>
  <primary_completion_date type="Actual">November 10, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Hemofiltration circuit survival time</measure>
    <time_frame>up to 120 hours from the beginning of hemofiltration session</time_frame>
    <description>in hours</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of metabolic alkalosis</measure>
    <time_frame>From the beginning of hemofiltration session until 6 hours after its end</time_frame>
    <description>Arterial blood pH&gt;7.5 or BE &gt; 40 mmol/L</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of hypernatremia and hyponatremia</measure>
    <time_frame>From the beginning of hemofiltration session until 6 hours after its end</time_frame>
    <description>Incidence of hypernatremia&gt; 150 mmol/L and hyponatremia &lt; 130 mmol/L in arterial blood sample</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of citrate accumulation</measure>
    <time_frame>From the beginning of hemofiltration session until 24 hours after its end</time_frame>
    <description>Incidence of total to ionized calcium ratio &gt; 2,5 in arterial blood sample</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">54</enrollment>
  <condition>Acute Kidney Injury</condition>
  <condition>Acute Kidney Failure</condition>
  <condition>Renal Replacement Therapy</condition>
  <condition>Hemofiltration</condition>
  <arm_group>
    <arm_group_label>HF RCA</arm_group_label>
    <description>Cardiovascular surgery patients treated with hemofiltration with regional citrate anticoagulation</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Hemofiltration with regional citrate anticoagulation</intervention_name>
    <description>To reduce risk of metabolic alkalosis during hemofiltration treatment, ACD-A citrate solution was proposed instead of most commonly used trisodium citrate solution and relatively low target citrate concentration (2.8 mmol/L) was adopted. In case of pH increase above 7.5 or bicarbonate concentration above 40 mmol/L filtrate flow was decreased from initial 35 ml/kg/hour down to 25 ml/kg/hour which reduced bicarbonate delivery by 25%. If metabolic alkalosis persisted, the second step involved reduction of blood flow from initial 5 times down to 4 times filtrate flow, which reduced citrate flow by the same factor.</description>
    <arm_group_label>HF RCA</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All consecutive cardio-vascular surgery patients treated with post-dilution hemofiltration&#xD;
        with regional citrate anticoagulation from August 2015 through November 2017&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  cardiac and vascular surgery patients treated with continuous hemofiltration with&#xD;
             regional citrate anticoagulation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  severe chronic liver disease, acute liver injury with INR &gt; 2, and refractory shock&#xD;
             with lactate increasing above 8 mmol/L&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Romuald Lango</name>
      <address>
        <city>Gdańsk</city>
        <state>Polska</state>
        <zip>80-516</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <reference>
    <citation>Kirwan CJ, Hutchison R, Ghabina S, Schwarze S, Beane A, Ramsay S, Thompson E, Prowle JR. Implementation of a Simplified Regional Citrate Anticoagulation Protocol for Post-Dilution Continuous Hemofiltration Using a Bicarbonate Buffered, Calcium Containing Replacement Solution. Blood Purif. 2016;42(4):349-355. doi: 10.1159/000452755. Epub 2016 Nov 19. Erratum In: Blood Purif. 2017;43(1-3):144.</citation>
    <PMID>27866200</PMID>
  </reference>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>February 6, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>February 11, 2019</last_update_submitted>
  <last_update_submitted_qc>February 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Gdansk</investigator_affiliation>
    <investigator_full_name>Romuald Lango</investigator_full_name>
    <investigator_title>Prof. Romuald Lango</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>Renal Insufficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No IPD are to be shared with other researcher</ipd_description>
  </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/NCT03836742
org study id: NKBBN/539/2016-17
nct id: NCT03836742
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Prospective observational study of all consecutive cardio-vascular surgical patients treated
      with post-dilution hemofiltration with regional citrate anticoagulation as first-choice
      anticoagulation method. The filter life-span was assessed in the context of postoperative
      cardiac surgical antithrombotic prophylaxis. Reasons for termination of hemofiltration
      sessions were assessed. The second aim of this study was to assess the influence ACD-A based
      anticoagulation protocol on acid-base and ion homeostasis in cardiac surgical patients with
      acute renal failure.
All consecutive cardio-vascular surgery patients treated with post-dilution hemofiltration
      with regional citrate anticoagulation (HF RCA) from August 2015 through November 2017 were
      included to prospective audit. Indication to hemofiltration treatment was based on clinical
      assessment of patients renal function and clinical status by attending physician and
      conformed conventional indications to renal replacement therapy (RRT) in intensive care unit
      (ICU). Severe chronic liver disease or acute liver injury with INR > 2 and refractory shock
      with lactate increasing above 8 mmol/L were considered as contraindication to RCA.

      Initially set blood flow was 5 times higher than filtrate flow, which makes filtration
      fraction of 20%. To reduce the risk of metabolic alkalosis, ACD-A citrate solution was
      proposed instead of most commonly used trisodium citrate solution, and relatively low target
      citrate concentration (2.8 mmol/L) was adopted. In case of pH increase above 7.5 or
      bicarbonate concentration above 40 mmol/L filtrate flow was decreased from initial 35
      ml/kg/hour down to 25 ml/kg/hour which should reduce bicarbonate synthesis by 25%. If
      metabolic alkalosis persisted, the second step involved reduction of blood flow from initial
      5 times down to 4 times filtrate flow, which reduced citrate flow by the same factor.

      In order to avoid hypomagnesemia resulting from magnesium binding to citrate, and its removal
      with ultrafiltrate not balanced with magnesium content in replacement fluid, the original
      protocol was modified by connecting magnesium sulfate solution 2g/50 ml 0.9% NaCl at the flow
      1 mL/hour.

      All sessions stopped due to patients death before 48 hours of HF treatment were excluded from
      the analysis. Similarly, all cases where hemofiltration session was stopped before 48 hours
      of treatment due to organizational reasons, recovery of renal function, change of therapy,
      and when patients were treated with heparin infusion due to surgical indications were
      excluded from further circuit survival analysis.

      Blood gas parameters together with pH, bicarbonate concentration, Na, Cl, K, Ca, hemoglobin
      concentration, hematocrit, lactate, and anion gap were analyzed every 6 hours. Post filter
      ionized calcium concentration was not assessed. Serum phosphate, magnesium and total calcium
      was assessed every 24 hours during hemofiltration treatment with RCA.
observational model: Case-Only
time perspective: Prospective
measure: Hemofiltration circuit survival time
time frame: up to 120 hours from the beginning of hemofiltration session
description: in hours
measure: Incidence of metabolic alkalosis
time frame: From the beginning of hemofiltration session until 6 hours after its end
description: Arterial blood pH>7.5 or BE > 40 mmol/L
measure: Incidence of hypernatremia and hyponatremia
time frame: From the beginning of hemofiltration session until 6 hours after its end
description: Incidence of hypernatremia> 150 mmol/L and hyponatremia < 130 mmol/L in arterial blood sample
measure: Incidence of citrate accumulation
time frame: From the beginning of hemofiltration session until 24 hours after its end
description: Incidence of total to ionized calcium ratio > 2,5 in arterial blood sample
arm group label: HF RCA
description: Cardiovascular surgery patients treated with hemofiltration with regional citrate anticoagulation
intervention type: Procedure
intervention name: Hemofiltration with regional citrate anticoagulation
description: To reduce risk of metabolic alkalosis during hemofiltration treatment, ACD-A citrate solution was proposed instead of most commonly used trisodium citrate solution and relatively low target citrate concentration (2.8 mmol/L) was adopted. In case of pH increase above 7.5 or bicarbonate concentration above 40 mmol/L filtrate flow was decreased from initial 35 ml/kg/hour down to 25 ml/kg/hour which reduced bicarbonate delivery by 25%. If metabolic alkalosis persisted, the second step involved reduction of blood flow from initial 5 times down to 4 times filtrate flow, which reduced citrate flow by the same factor.
arm group label: HF RCA
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
facility: 
country: Poland
citation: Kirwan CJ, Hutchison R, Ghabina S, Schwarze S, Beane A, Ramsay S, Thompson E, Prowle JR. Implementation of a Simplified Regional Citrate Anticoagulation Protocol for Post-Dilution Continuous Hemofiltration Using a Bicarbonate Buffered, Calcium Containing Replacement Solution. Blood Purif. 2016;42(4):349-355. doi: 10.1159/000452755. Epub 2016 Nov 19. Erratum In: Blood Purif. 2017;43(1-3):144.
PMID: 27866200
responsible party type: Principal Investigator
investigator affiliation: Medical University of Gdansk
investigator full name: Romuald Lango
investigator title: Prof. Romuald Lango
mesh term: Acute Kidney Injury
mesh term: Renal Insufficiency
sharing ipd: No
ipd description: No IPD are to be shared with other researcher