<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/NCT02253082</url>
  </required_header>
  <id_info>
    <org_study_id>VIPER-OCTA</org_study_id>
    <secondary_id>H-3-2014-018</secondary_id>
    <nct_id>NCT02253082</nct_id>
  </id_info>
  <brief_title>Vasculopathic Injury and Plasma as Endothelial Rescue - OCTAplas Trial (EudraCT no. 2014-000452-28)</brief_title>
  <acronym>VIPER-OCTA</acronym>
  <official_title>Effects of OctaplasLG® on Endothelial Integrity in Patients Undergoing Emergency Surgery for Thoracic Aortic Dissections - a Randomized, Controlled, Single-blinded Investigator-initiated Pilot Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Octapharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Effects of OctaplasLG® on endothelial integrity in patients undergoing emergency surgery for&#xD;
      thoracic aortic dissections - a randomized, controlled, single-blinded investigator-initiated&#xD;
      pilot trial&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Trial Name: VIPER-OCTA trial - Vasculopathic Injury and Plasma as Endothelial Rescue -&#xD;
      OCTAplas trial&#xD;
&#xD;
      Background&#xD;
&#xD;
        -  Patients operated for thoracic aortic dissections in deep hypothermic circulatory arrest&#xD;
           are prone to develop postoperative renal failure secondary to severe endothelial&#xD;
           dysfunction and capillary leakage, and currently no therapy addressing this complication&#xD;
           has proven successful&#xD;
&#xD;
        -  Data from animal models of shock and massively bleeding patients indicate that plasma&#xD;
           may be beneficial for re-establishing endothelial integrity&#xD;
&#xD;
        -  Patients operated for thoracic aortic dissections generally develop requirement for&#xD;
           massive transfusion during surgery&#xD;
&#xD;
        -  Current guidelines, however, recommend against plasma transfusion to patients not&#xD;
           needing coagulation factor replacement due to the inherent risk of transfusion&#xD;
           complications&#xD;
&#xD;
        -  OctaplasLG® is an immune complex-free and cell-free, pathogen inactivated standardized&#xD;
           plasma product that has been shown not to be related to the transfusion complications&#xD;
           seen secondary to standard fresh frozen plasma (FFP), thus, OctaplasLG® may be a&#xD;
           beneficial, alternative resuscitation fluid in patients with severe endothelial&#xD;
           dysfunction/damage&#xD;
&#xD;
        -  The purpose is to bridge the knowledge gap regarding the effect of OctaplasLG® on&#xD;
           endothelial integrity and safety&#xD;
&#xD;
      Design Single-centre randomised, single-blinded, controlled, investigator-initiated pilot&#xD;
      trial of 42 patients undergoing emergency surgery for thoracic aortic dissections randomized&#xD;
      to administration of OctaplasLG®, as compared to standard FFP, as coagulation factor&#xD;
      replacement related to bleeding, when need for coagulation factor replacement is deemed&#xD;
      necessary by the clinician according to local protocol.&#xD;
&#xD;
      Inclusion criteria&#xD;
&#xD;
        -  Patient eligible for emergency surgery on cardiopulmonary bypass pump for a thoracic&#xD;
           aortic dissections AND&#xD;
&#xD;
        -  Age &gt; 18 years AND&#xD;
&#xD;
        -  Consent obtainable from patient or by proxy (independent physicians and/or next of kin)&#xD;
&#xD;
      Exclusion criteria&#xD;
&#xD;
        -  Documented refusal of blood transfusion OR&#xD;
&#xD;
        -  FFP transfusion before randomization OR&#xD;
&#xD;
        -  Aortic dissection due to trauma OR&#xD;
&#xD;
        -  Treatment with GPIIb/IIIa inhibitors &lt; 24h from screening OR&#xD;
&#xD;
        -  Withdrawal from active therapy OR&#xD;
&#xD;
        -  Expected to die &lt; 24h OR&#xD;
&#xD;
        -  Previously within 30 days included in a randomized trial, if known at the time of&#xD;
           enrolment.&#xD;
&#xD;
        -  Known immunoglobulin A (IgA) deficiency with documented antibodies against IgA&#xD;
&#xD;
        -  Known hypersensitivity to OctaplasLG®: the active substance, any of the excipients&#xD;
           (Sodium citrate dihydrate, Sodium dihydrogenphosphate dihydrate or Glycine) or residues&#xD;
           from the manufacturing process (Tri (N-Butyl) Phosphate (TNBP) and Octoxynol (Triton&#xD;
           X-100))&#xD;
&#xD;
        -  Known severe deficiencies of protein S&#xD;
&#xD;
        -  Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a negative&#xD;
           serum-hCG).&#xD;
&#xD;
      Randomization Blood Bank staff will perform 24 hour on-site randomisation by envelope-opening&#xD;
      to allow for immediate allocation to either receiving OctaplasLG® (intervention) or standard&#xD;
      FFP (control) as coagulation factor replacement.&#xD;
&#xD;
      Outcome measures&#xD;
&#xD;
      Primary outcome measure:&#xD;
&#xD;
      • Plasma levels of endothelial markers (Syndecan-1, soluble thrombomodulin (sTM),&#xD;
      sE-selectin, sVE-cadherin) at 24 hours after arrival in ICU for postoperative care, as&#xD;
      compared to baseline&#xD;
&#xD;
      Secondary outcome measures:&#xD;
&#xD;
        -  Plasma levels of endothelial markers (Syndecan-1, sTM, sE-selectin, sVE-cadherin) at 48&#xD;
           hours postoperatively, as compared to baseline&#xD;
&#xD;
        -  Acute Kidney Injury (AKI) according to RIFLE Criteria in the first 7 postoperative days,&#xD;
           see appendix 1&#xD;
&#xD;
        -  Renal replacement therapy&#xD;
&#xD;
        -  Sepsis-Related Organ Failure Assessment (SOFA), worst score during ICU stay, see&#xD;
           appendix 2&#xD;
&#xD;
        -  30-day and 90-day mortality&#xD;
&#xD;
        -  P-CRP, IL-6, P-Catecholamines at 24 hours and 48 hours&#xD;
&#xD;
        -  Length of stay in ICU and hospital&#xD;
&#xD;
        -  Severe adverse reactions&#xD;
&#xD;
      Tertiary outcome measures&#xD;
&#xD;
        -  TRALI&#xD;
&#xD;
        -  TACO&#xD;
&#xD;
      Trial size The calculation is based in part by data collected in a quality control&#xD;
      investigation of the effect of OctaplasLG® vs. FFP. The power calculation is based on the&#xD;
      finding of a significantly higher relative level of sTM in the FFP compared to the&#xD;
      OctaplasLG® group (p=0.025). The relative values of sTM post-CPB: FFP group: mean 3.35 (SD&#xD;
      2.12); OctaplasLG® group: mean 1.70 (SD 0.49); SD across the entire group of patients: 1.574.&#xD;
      To detect the above difference with a power of 0.90 (1-β) and alpha of 0.05 requires n=21&#xD;
      patients in each group. The investigators have chosen to include 42 patients, 21 evaluable&#xD;
      patients in each randomization group in case of attrition, in the present trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma levels of endothelial markers (Syndecan-1, sTM, sE-selectin, sVE-cadherin)</measure>
    <time_frame>At 24 hours after arrival in ICU for postoperative care, as compared to baseline</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma levels of endothelial markers (Syndecan-1, soluble thrombomodulin (sTM), sE-selectin, sVE-cadherin)</measure>
    <time_frame>At 48 hours postoperatively, as compared to baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Kidney Injury (AKI) according to RIFLE Criteria</measure>
    <time_frame>In the first 7 postoperative days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal replacement therapy</measure>
    <time_frame>In the first 7 postoperative days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sepsis-Related Organ Failure Assessment (SOFA)</measure>
    <time_frame>Worst score In the first 7 postoperative days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>30-day and 90-day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P-Creactive protein (CRP), Interleukin-6 (IL-6), P-Catecholamines</measure>
    <time_frame>At 24 hours and 48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay in ICU and hospital</measure>
    <time_frame>Days, assessed at 30-days and 90-days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe adverse reactions</measure>
    <time_frame>In the first 30 postoperative days</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Transfusion associated acute lung injury (TRALI)</measure>
    <time_frame>In the first 30 postoperative days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Transfusion associated circulatory overload (TACO)</measure>
    <time_frame>In the first 30 postoperative days</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Aortic Aneurysm, Thoracic</condition>
  <condition>Endothelial Dysfunction</condition>
  <arm_group>
    <arm_group_label>OctaplasLG®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>replacement to bleeding</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard fresh frozen plasma</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>replacement to bleeding</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OctaplasLG®</intervention_name>
    <description>OctaplasLG® is an industrial donor plasma product pooled from approximately 400 single donor units. It possess' unique features when compared to standard FFP, such as having standardized concentrations of natural pro- and anti-coagulation factors, standardized volume and as being pathogen free. Very importantly, the manufacturing method of OctaplasLG® removes immune complexes and cells in several steps of microfiltration in addition to viral, bacterial and prion pathogen inactivation.</description>
    <arm_group_label>OctaplasLG®</arm_group_label>
    <other_name>Octaplas</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fresh frozen plasma</intervention_name>
    <description>Standard FFP from the Blood Bank</description>
    <arm_group_label>Standard fresh frozen plasma</arm_group_label>
    <other_name>FFP</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient eligible for emergency surgery on cardiopulmonary bypass pump for a thoracic&#xD;
             aortic dissections AND&#xD;
&#xD;
          -  Age &gt; 18 years AND&#xD;
&#xD;
          -  Consent obtainable from patient or by proxy (independent physicians and/or next of&#xD;
             kin)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Documented refusal of blood transfusion OR&#xD;
&#xD;
          -  FFP transfusion before randomization OR&#xD;
&#xD;
          -  Aortic dissection due to trauma OR&#xD;
&#xD;
          -  Treatment with GPIIb/IIIa inhibitors &lt; 24h from screening OR&#xD;
&#xD;
          -  Withdrawal from active therapy OR&#xD;
&#xD;
          -  Expected to die &lt; 24h OR&#xD;
&#xD;
          -  Previously within 30 days included in a randomized trial, if known at the time of&#xD;
             enrolment&#xD;
&#xD;
          -  Known IgA deficiency with documented antibodies against IgA&#xD;
&#xD;
          -  Known hypersensitivity to OctaplasLG®: the active substance, any of the excipients&#xD;
             (Sodium citrate dihydrate, Sodium dihydrogenphosphate dihydrate or Glycine) or&#xD;
             residues from the manufacturing process (Tri (N-Butyl) Phosphate (TNBP) and Octoxynol&#xD;
             (Triton X-100))&#xD;
&#xD;
          -  Known severe deficiencies of protein S&#xD;
&#xD;
          -  Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a&#xD;
             negative serum-hCG)&#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>Jakob Stensballe, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rigshospitalet, Copenhagen University Hospital</name>
      <address>
        <city>Copenhagen</city>
        <zip>DK-2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>December 19, 2016</last_update_submitted>
  <last_update_submitted_qc>December 19, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 20, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Jakob Stensballe, MD, PhD</investigator_full_name>
    <investigator_title>MD, PhD, Consultant</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aneurysm</mesh_term>
    <mesh_term>Aortic Aneurysm</mesh_term>
    <mesh_term>Aortic Aneurysm, Thoracic</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/NCT02253082
org study id: VIPER-OCTA
secondary id: H-3-2014-018
nct id: NCT02253082
lead sponsor: 
collaborator: 
has dmc: Yes
Effects of OctaplasLG® on endothelial integrity in patients undergoing emergency surgery for
      thoracic aortic dissections - a randomized, controlled, single-blinded investigator-initiated
      pilot trial
Trial Name: VIPER-OCTA trial - Vasculopathic Injury and Plasma as Endothelial Rescue -
      OCTAplas trial

      Background

        -  Patients operated for thoracic aortic dissections in deep hypothermic circulatory arrest
           are prone to develop postoperative renal failure secondary to severe endothelial
           dysfunction and capillary leakage, and currently no therapy addressing this complication
           has proven successful

        -  Data from animal models of shock and massively bleeding patients indicate that plasma
           may be beneficial for re-establishing endothelial integrity

        -  Patients operated for thoracic aortic dissections generally develop requirement for
           massive transfusion during surgery

        -  Current guidelines, however, recommend against plasma transfusion to patients not
           needing coagulation factor replacement due to the inherent risk of transfusion
           complications

        -  OctaplasLG® is an immune complex-free and cell-free, pathogen inactivated standardized
           plasma product that has been shown not to be related to the transfusion complications
           seen secondary to standard fresh frozen plasma (FFP), thus, OctaplasLG® may be a
           beneficial, alternative resuscitation fluid in patients with severe endothelial
           dysfunction/damage

        -  The purpose is to bridge the knowledge gap regarding the effect of OctaplasLG® on
           endothelial integrity and safety

      Design Single-centre randomised, single-blinded, controlled, investigator-initiated pilot
      trial of 42 patients undergoing emergency surgery for thoracic aortic dissections randomized
      to administration of OctaplasLG®, as compared to standard FFP, as coagulation factor
      replacement related to bleeding, when need for coagulation factor replacement is deemed
      necessary by the clinician according to local protocol.

      Inclusion criteria

        -  Patient eligible for emergency surgery on cardiopulmonary bypass pump for a thoracic
           aortic dissections AND

        -  Age > 18 years AND

        -  Consent obtainable from patient or by proxy (independent physicians and/or next of kin)

      Exclusion criteria

        -  Documented refusal of blood transfusion OR

        -  FFP transfusion before randomization OR

        -  Aortic dissection due to trauma OR

        -  Treatment with GPIIb/IIIa inhibitors < 24h from screening OR

        -  Withdrawal from active therapy OR

        -  Expected to die < 24h OR

        -  Previously within 30 days included in a randomized trial, if known at the time of
           enrolment.

        -  Known immunoglobulin A (IgA) deficiency with documented antibodies against IgA

        -  Known hypersensitivity to OctaplasLG®: the active substance, any of the excipients
           (Sodium citrate dihydrate, Sodium dihydrogenphosphate dihydrate or Glycine) or residues
           from the manufacturing process (Tri (N-Butyl) Phosphate (TNBP) and Octoxynol (Triton
           X-100))

        -  Known severe deficiencies of protein S

        -  Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a negative
           serum-hCG).

      Randomization Blood Bank staff will perform 24 hour on-site randomisation by envelope-opening
      to allow for immediate allocation to either receiving OctaplasLG® (intervention) or standard
      FFP (control) as coagulation factor replacement.

      Outcome measures

      Primary outcome measure:

      • Plasma levels of endothelial markers (Syndecan-1, soluble thrombomodulin (sTM),
      sE-selectin, sVE-cadherin) at 24 hours after arrival in ICU for postoperative care, as
      compared to baseline

      Secondary outcome measures:

        -  Plasma levels of endothelial markers (Syndecan-1, sTM, sE-selectin, sVE-cadherin) at 48
           hours postoperatively, as compared to baseline

        -  Acute Kidney Injury (AKI) according to RIFLE Criteria in the first 7 postoperative days,
           see appendix 1

        -  Renal replacement therapy

        -  Sepsis-Related Organ Failure Assessment (SOFA), worst score during ICU stay, see
           appendix 2

        -  30-day and 90-day mortality

        -  P-CRP, IL-6, P-Catecholamines at 24 hours and 48 hours

        -  Length of stay in ICU and hospital

        -  Severe adverse reactions

      Tertiary outcome measures

        -  TRALI

        -  TACO

      Trial size The calculation is based in part by data collected in a quality control
      investigation of the effect of OctaplasLG® vs. FFP. The power calculation is based on the
      finding of a significantly higher relative level of sTM in the FFP compared to the
      OctaplasLG® group (p=0.025). The relative values of sTM post-CPB: FFP group: mean 3.35 (SD
      2.12); OctaplasLG® group: mean 1.70 (SD 0.49); SD across the entire group of patients: 1.574.
      To detect the above difference with a power of 0.90 (1-β) and alpha of 0.05 requires n=21
      patients in each group. The investigators have chosen to include 42 patients, 21 evaluable
      patients in each randomization group in case of attrition, in the present trial.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Plasma levels of endothelial markers (Syndecan-1, sTM, sE-selectin, sVE-cadherin)
time frame: At 24 hours after arrival in ICU for postoperative care, as compared to baseline
measure: Plasma levels of endothelial markers (Syndecan-1, soluble thrombomodulin (sTM), sE-selectin, sVE-cadherin)
time frame: At 48 hours postoperatively, as compared to baseline
measure: Acute Kidney Injury (AKI) according to RIFLE Criteria
time frame: In the first 7 postoperative days
measure: Renal replacement therapy
time frame: In the first 7 postoperative days
measure: Sepsis-Related Organ Failure Assessment (SOFA)
time frame: Worst score In the first 7 postoperative days
measure: Mortality
time frame: 30-day and 90-day
measure: P-Creactive protein (CRP), Interleukin-6 (IL-6), P-Catecholamines
time frame: At 24 hours and 48 hours
measure: Length of stay in ICU and hospital
time frame: Days, assessed at 30-days and 90-days
measure: Severe adverse reactions
time frame: In the first 30 postoperative days
measure: Transfusion associated acute lung injury (TRALI)
time frame: In the first 30 postoperative days
measure: Transfusion associated circulatory overload (TACO)
time frame: In the first 30 postoperative days
arm group label: OctaplasLG®
arm group type: Active Comparator
description: replacement to bleeding
arm group label: Standard fresh frozen plasma
arm group type: Placebo Comparator
description: replacement to bleeding
intervention type: Drug
intervention name: OctaplasLG®
description: OctaplasLG® is an industrial donor plasma product pooled from approximately 400 single donor units. It possess' unique features when compared to standard FFP, such as having standardized concentrations of natural pro- and anti-coagulation factors, standardized volume and as being pathogen free. Very importantly, the manufacturing method of OctaplasLG® removes immune complexes and cells in several steps of microfiltration in addition to viral, bacterial and prion pathogen inactivation.
arm group label: OctaplasLG®
other name: Octaplas
intervention type: Biological
intervention name: Fresh frozen plasma
description: Standard FFP from the Blood Bank
arm group label: Standard fresh frozen plasma
other name: FFP
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jakob Stensballe, MD, PhD
role: Principal Investigator
affiliation: Rigshospitalet, Denmark
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Jakob Stensballe, MD, PhD
investigator title: MD, PhD, Consultant
mesh term: Aneurysm
mesh term: Aortic Aneurysm
mesh term: Aortic Aneurysm, Thoracic
sharing ipd: No