<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/NCT04506125</url>
  </required_header>
  <id_info>
    <org_study_id>29BRC20.0086</org_study_id>
    <nct_id>NCT04506125</nct_id>
  </id_info>
  <brief_title>Liberal Versus Restrictive Transfusion Threshold in Oncologic surgerY</brief_title>
  <acronym>LIBERTY1</acronym>
  <official_title>Liberal Versus Restrictive Transfusion Threshold in High-risk Oncologic surgerY: a Multicenter, Randomized, Controlled, Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Brest</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Brest</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>
      Anemia is common in oncology. Up to three-quarters of cancer patients are exposed to an&#xD;
      episode of anemia. In oncology surgery, perioperative bleeding is a major risk factor for&#xD;
      anemia. Indeed, 13 to 40% of patients are transfused in perioperative oncologic surgery.&#xD;
&#xD;
      There is an association between anemia and prognosis. Several epidemiological studies have&#xD;
      shown a strong association between anemia and altered quality of life. In oncology cohort&#xD;
      studies, anemic patients had a significantly lower quality of life compared to patients&#xD;
      without anemia. In non-cardiac surgery, preoperative anaemia was significantly associated&#xD;
      with post-operative mortality. There is also an association between preoperative anaemia and&#xD;
      the occurrence of post-operative complications. In oncology surgery, cohort studies conducted&#xD;
      in colorectal surgery and neurosurgery found an association between the occurrence of&#xD;
      perioperative anemia and post-operative morbidity and mortality.&#xD;
&#xD;
      The optimal transfusion strategy is unknown in oncology patients. Several multicentre&#xD;
      randomised trials, conducted in resuscitation patients or in perioperative settings, have&#xD;
      compared a &quot;restrictive&quot; to a &quot;liberal&quot; transfusion strategy. These studies did not show a&#xD;
      superiority of one strategy over another on patient outcomes but a lower exposure to red&#xD;
      blood cell concentrates in patients transfused with the restrictive transfusion strategy.&#xD;
      Thus, the French High Authority for Health (HAS) has adopted a haemoglobin level of 7 g/dl as&#xD;
      the transfusion threshold for any transfusion of red blood cell concentrate carried out in&#xD;
      the operating theatre and in intensive care in the absence of special cases such as the&#xD;
      presence of acute coronary syndrome. For oncology patients, no recommendation could be made&#xD;
      due to the lack of evidence-based literature and the optimal transfusion strategy for these&#xD;
      patients remains unknown. Only 2 monocentric trials performed in oncology (critical care and&#xD;
      perioperative) suggest a benefit of a liberal strategy (transfusion for a haemoglobin level &lt;&#xD;
      9 g/dl) on the short-term vital prognosis, but these studies suffer from numerous limitations&#xD;
      leaving the question unresolved.&#xD;
&#xD;
      Before conducting a large phase III trial, a pilot study is needed to validate the&#xD;
      methodology of this multicentre clinical trial and to assess its feasibility.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 18, 2021</start_date>
  <completion_date type="Actual">August 29, 2022</completion_date>
  <primary_completion_date type="Actual">August 29, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Pilot, multicentre, randomized, controlled, single-blind, pilot study comparing two strategies for transfusion of red blood cell concentrates</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Methodology of the pilot study</measure>
    <time_frame>up to 30 days</time_frame>
    <description>The difference in mean hemoglobin levels during the perioperative period up to 30 days postoperatively between the two groups will be assessed</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Epidemiological data of the pilot study</measure>
    <time_frame>up to 90 days</time_frame>
    <description>The percentage of patients with oncologic surgery admitted to intensive care unit requiring transfusion of red blood cell concentrates eerioperatively among aatients with oncologic surgery admitted to intensive care unit will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epidemiological data of the pilot study</measure>
    <time_frame>up to 90 days</time_frame>
    <description>Percentage of eligible patients included in the study will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epidemiological data of the pilot study</measure>
    <time_frame>up to 90 days</time_frame>
    <description>Delay between surgery and randomization will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epidemiological data of the pilot study</measure>
    <time_frame>up to 90 days</time_frame>
    <description>Percentage of protocol violations in each group will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epidemiological data of the pilot study</measure>
    <time_frame>up to 90 days</time_frame>
    <description>Average number of erythrocyte concentrates delivered to each group intraoperatively, in intensive care and during hospitalization will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epidemiological data of the pilot study</measure>
    <time_frame>up to 90 days</time_frame>
    <description>Post-operative complications, occurring between surgery and the 30th day after surgery or before discharge from hospital will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Reaction Monitoring</measure>
    <time_frame>up to 30 days</time_frame>
    <description>To compare the occurrence of transfusion-related adverse events in each group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the functional status</measure>
    <time_frame>up to 30 days</time_frame>
    <description>Test functional status assessment at 30 days postoperatively using the World Health Organization Disability Assessment Schedule (WHODAS) questionnaire.&#xD;
This questionnaire asks about difficulties due to health/mental health conditions. Health conditions include diseases or illnesses, other health problems that may be short or long lasting, injuries, mental or emotional problems, and problems with alcohol or drugs. The patient must think back over the past 30 days and answer the questions thinking about how much difficulty you had doing the following activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the functional status after surgery ans anesthesia</measure>
    <time_frame>up to 30 days</time_frame>
    <description>Test functional status assessment at 30 days postoperatively using the Quality of recovery questionnaire.&#xD;
The Quality of Recovery-15 (QoR-15) is a psychometrically tested and validated questionnaire.&#xD;
The QoR-15 was psychometrically evaluated using data collected from patients who responded at all four time intervals.This included: Acceptability and Feasibility; Validity; Reliability; Responsiveness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monitoring of the quality of the study's execution</measure>
    <time_frame>up to 30 days</time_frame>
    <description>Compare the percentage of protocol violations in the 2 groups</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Oncologic Complications</condition>
  <condition>Anemia</condition>
  <arm_group>
    <arm_group_label>Liberal Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>transfusion of an erythrocyte concentrate in case of haemoglobin below 9.5 g/dL</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Restrictive group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>transfusion of an erythrocyte concentrate in case of haemoglobin below 7.5 g/dL</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Haemoglobin 9.5 g/dL</intervention_name>
    <description>transfusion of red blood cell concentrate if the haemoglobin level is less than 9,5 g/dL</description>
    <arm_group_label>Liberal Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Haemoglobine 7.5g/dL</intervention_name>
    <description>transfusion of red blood cell concentrate if the haemoglobin level is less than 7,5 g/dL</description>
    <arm_group_label>Restrictive group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years old&#xD;
&#xD;
          -  Anticipated or proven admission to immediate postoperative resuscitation after&#xD;
             scheduled or emergency oncology surgery, for the removal of a neoplastic lesion among&#xD;
             the following surgical procedures:&#xD;
&#xD;
               -  Visceral surgery: Hepatectomy, duodenopancreatectomy, gastrectomy, esophagectomy,&#xD;
                  colectomy&#xD;
&#xD;
               -  Urological surgery: Radical prostatectomy, cystectomy, nephrectomy.&#xD;
&#xD;
               -  Gynaecological surgery: Ovariectomy, hysterectomy, mastectomy, pelvectomy&#xD;
&#xD;
               -  Thoracic surgery: Pneumonectomy, lobectomy&#xD;
&#xD;
               -  ENT Surgery: Total laryngectomy, pharyngectomy, glossectomy&#xD;
&#xD;
               -  Spinal surgery: corporectomy wherever it is performed.&#xD;
&#xD;
          -  Hemoglobin level &lt; 9.5 g/dl between the day before surgery (D-1) and discharge from&#xD;
             resuscitation at no more than 30 days postoperatively&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  - Myocardial infarction and/or unstable angina in the 4 weeks prior to surgery&#xD;
&#xD;
          -  Refusal to participate in the study&#xD;
&#xD;
          -  Minor patient (age &lt; 18 years)&#xD;
&#xD;
          -  Refusal to transfuse red blood cell concentrates (Jehovah's Witness)&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Patients under guardianship or curatorship&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CHU d'Angers</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU de Brest</name>
      <address>
        <city>Brest</city>
        <zip>29609</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>July 28, 2023</last_update_submitted>
  <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Transfusion</keyword>
  <keyword>Pilot study</keyword>
  <keyword>critically ill patients</keyword>
  <keyword>oncologic surgery</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chrysarobin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All collected data that underlie results in a publication</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Data will be available beginning two years and ending fifteen years following the final study report completion</ipd_time_frame>
    <ipd_access_criteria>Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement</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/NCT04506125
org study id: 29BRC20.0086
nct id: NCT04506125
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Anemia is common in oncology. Up to three-quarters of cancer patients are exposed to an
      episode of anemia. In oncology surgery, perioperative bleeding is a major risk factor for
      anemia. Indeed, 13 to 40% of patients are transfused in perioperative oncologic surgery.

      There is an association between anemia and prognosis. Several epidemiological studies have
      shown a strong association between anemia and altered quality of life. In oncology cohort
      studies, anemic patients had a significantly lower quality of life compared to patients
      without anemia. In non-cardiac surgery, preoperative anaemia was significantly associated
      with post-operative mortality. There is also an association between preoperative anaemia and
      the occurrence of post-operative complications. In oncology surgery, cohort studies conducted
      in colorectal surgery and neurosurgery found an association between the occurrence of
      perioperative anemia and post-operative morbidity and mortality.

      The optimal transfusion strategy is unknown in oncology patients. Several multicentre
      randomised trials, conducted in resuscitation patients or in perioperative settings, have
      compared a "restrictive" to a "liberal" transfusion strategy. These studies did not show a
      superiority of one strategy over another on patient outcomes but a lower exposure to red
      blood cell concentrates in patients transfused with the restrictive transfusion strategy.
      Thus, the French High Authority for Health (HAS) has adopted a haemoglobin level of 7 g/dl as
      the transfusion threshold for any transfusion of red blood cell concentrate carried out in
      the operating theatre and in intensive care in the absence of special cases such as the
      presence of acute coronary syndrome. For oncology patients, no recommendation could be made
      due to the lack of evidence-based literature and the optimal transfusion strategy for these
      patients remains unknown. Only 2 monocentric trials performed in oncology (critical care and
      perioperative) suggest a benefit of a liberal strategy (transfusion for a haemoglobin level <
      9 g/dl) on the short-term vital prognosis, but these studies suffer from numerous limitations
      leaving the question unresolved.

      Before conducting a large phase III trial, a pilot study is needed to validate the
      methodology of this multicentre clinical trial and to assess its feasibility.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Pilot, multicentre, randomized, controlled, single-blind, pilot study comparing two strategies for transfusion of red blood cell concentrates
primary purpose: Prevention
masking: None (Open Label)
measure: Methodology of the pilot study
time frame: up to 30 days
description: The difference in mean hemoglobin levels during the perioperative period up to 30 days postoperatively between the two groups will be assessed
measure: Epidemiological data of the pilot study
time frame: up to 90 days
description: The percentage of patients with oncologic surgery admitted to intensive care unit requiring transfusion of red blood cell concentrates eerioperatively among aatients with oncologic surgery admitted to intensive care unit will be assessed
measure: Epidemiological data of the pilot study
time frame: up to 90 days
description: Percentage of eligible patients included in the study will be assessed
measure: Epidemiological data of the pilot study
time frame: up to 90 days
description: Delay between surgery and randomization will be assessed
measure: Epidemiological data of the pilot study
time frame: up to 90 days
description: Percentage of protocol violations in each group will be assessed
measure: Epidemiological data of the pilot study
time frame: up to 90 days
description: Average number of erythrocyte concentrates delivered to each group intraoperatively, in intensive care and during hospitalization will be assessed
measure: Epidemiological data of the pilot study
time frame: up to 90 days
description: Post-operative complications, occurring between surgery and the 30th day after surgery or before discharge from hospital will be assessed
measure: Adverse Reaction Monitoring
time frame: up to 30 days
description: To compare the occurrence of transfusion-related adverse events in each group
measure: Evaluation of the functional status
time frame: up to 30 days
description: Test functional status assessment at 30 days postoperatively using the World Health Organization Disability Assessment Schedule (WHODAS) questionnaire.
This questionnaire asks about difficulties due to health/mental health conditions. Health conditions include diseases or illnesses, other health problems that may be short or long lasting, injuries, mental or emotional problems, and problems with alcohol or drugs. The patient must think back over the past 30 days and answer the questions thinking about how much difficulty you had doing the following activities.
measure: Evaluation of the functional status after surgery ans anesthesia
time frame: up to 30 days
description: Test functional status assessment at 30 days postoperatively using the Quality of recovery questionnaire.
The Quality of Recovery-15 (QoR-15) is a psychometrically tested and validated questionnaire.
The QoR-15 was psychometrically evaluated using data collected from patients who responded at all four time intervals.This included: Acceptability and Feasibility; Validity; Reliability; Responsiveness
measure: Monitoring of the quality of the study's execution
time frame: up to 30 days
description: Compare the percentage of protocol violations in the 2 groups
arm group label: Liberal Group
arm group type: Experimental
description: transfusion of an erythrocyte concentrate in case of haemoglobin below 9.5 g/dL
arm group label: Restrictive group
arm group type: Active Comparator
description: transfusion of an erythrocyte concentrate in case of haemoglobin below 7.5 g/dL
intervention type: Other
intervention name: Haemoglobin 9.5 g/dL
description: transfusion of red blood cell concentrate if the haemoglobin level is less than 9,5 g/dL
arm group label: Liberal Group
intervention type: Other
intervention name: Haemoglobine 7.5g/dL
description: transfusion of red blood cell concentrate if the haemoglobin level is less than 7,5 g/dL
arm group label: Restrictive group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Chrysarobin
sharing ipd: Yes
ipd description: All collected data that underlie results in a publication
ipd info type: Study Protocol
ipd time frame: Data will be available beginning two years and ending fifteen years following the final study report completion
ipd access criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement