xml: <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/NCT06012760</url>
    </required_header>
    <id_info>
      <org_study_id>A2023519</org_study_id>
      <nct_id>NCT06012760</nct_id>
    </id_info>
    <brief_title>The Effect of Combined Iron Protocols on Perioperative Allogeneic Transfusion</brief_title>
    <acronym>CIPAT</acronym>
    <official_title>Effect of Iron Sucrose Combined With Human Erythropoietin and Vitamin C on Perioperative Allogeneic Red Blood Cell Infusion in Major Cardiac Surgery</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Second Affiliated Hospital, School of Medicine, Zhejiang University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Second Affiliated Hospital, School of Medicine, Zhejiang University</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>
        Previous studies have shown that perioperative intravenous iron has a beneficial effect on&#xD;
        patients with perioperative anaemia. To assess whether a combined iron supplementation&#xD;
        regimen can reduce perioperative allogeneic blood transfusions in patients with iron&#xD;
        deficiency anaemia undergoing major cardiac surgery under haemodynamic anaesthesia, a&#xD;
        multicentre randomised clinical trial (CIPAT study) will be conducted. In the CIPAT study,&#xD;
        patients undergoing elective major cardiac surgery under general anaesthesia will be randomly&#xD;
        allocated to a control group and a combined iron supplementation group. Patients in the&#xD;
        combined iron supplementation group will receive a combination iron supplementation regimen&#xD;
        of iron sucrose in combination with Human Erythropoietin and vitamin C three times in the&#xD;
        week prior to surgery, while patients in the control group will receive the same dose of&#xD;
        placebo three times in the week prior to surgery. The primary endpoint is the volume of&#xD;
        allogeneic erythrocyte infusion from the start of surgery to 5 days postoperatively. It is&#xD;
        hypothesised that patients in the combined iron supplementation group will have fewer&#xD;
        perioperative allogeneic red blood cell transfusions than those in the control group.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The objective of this study is to examine the potential of iron sucrose in conjunction with&#xD;
        human erythropoietin and vitamin C to mitigate the need for perioperative allo-erythrocyte&#xD;
        infusion in patients undergoing their initial elective major cardiac surgery. This will be&#xD;
        achieved by assessing outcome measures including the quantity of perioperative&#xD;
        allo-erythrocyte transfusion and the alteration in perioperative haemoglobin levels.&#xD;
  &#xD;
        The sample size calculation for this study involved a randomised controlled trial with a&#xD;
        parallel design. The intervention group consisted of individuals receiving combination&#xD;
        therapy, while the control group received a placebo. The primary outcome indicator observed&#xD;
        in the study population was perioperative blood transfusion. Our centre's pre-trial data&#xD;
        survey indicated a perioperative blood transfusion rate of 1.8 U in the control group. It was&#xD;
        hypothesized that the combination therapy would result in a reduction of blood transfusion by&#xD;
        at least 0.5 U.The blood transfusion in the combination therapy group was 1.3. Setting α=0.05&#xD;
        (bilaterally) with a degree of certainty=0.90. Using the bilaterally Mann-Whitney U or the&#xD;
        Wilcoxon Rank-Sum test at the 0.05 level of significance (α ), when the mean difference of&#xD;
        the null hypothesis was 0. Based on Poisson distribution, the sample size N1 = 188 for the&#xD;
        combination treatment group and N2 = 188 cases for the placebo control group was calculated&#xD;
        using PASS 21 software. Assuming a 20% loss-to-follow-up rate of study participants, a sample&#xD;
        size of at least N1 = 188 ÷ 0.8 = 235 cases and N2 = 188 ÷ 0.8 = 235 cases would be required.&#xD;
        In the end, 240 study subjects were included in the combination treatment group and 240 in&#xD;
        the placebo control group, for a total of 480 cases.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">August 30, 2023</start_date>
    <completion_date type="Anticipated">March 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">January 31, 2025</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Perioperative allogeneic red blood cell transfusion volume</measure>
      <time_frame>From the initiation of the surgical procedure until five days post-surgery.</time_frame>
      <description>The volume of allogeneic red blood cell transfusions during the perioperative period.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>The quantity and percentage of allogeneic blood products utilized during the perioperative period.</measure>
      <time_frame>From the initiation of the surgical procedure until the patient's release from the hospital or the 30th day following the operation, whichever occurs earlier.</time_frame>
      <description>This encompasses blood components such as plasma and platelets, erythrocytes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The alterations in perioperative haemoglobin levels.</measure>
      <time_frame>From the point of randomisation until 90± 7 days following the surgical procedure.</time_frame>
      <description>Haemoglobin levels were assessed at various time intervals.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The alterations in ferritin levels and serum total iron binding capacity during the perioperative period.</measure>
      <time_frame>From the point of randomisation until 90± 7 days following the surgical procedure.</time_frame>
      <description>Ferritin and serum total iron binding capacity values were assessed at various time intervals.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The alterations in reticulocyte levels during the perioperative period.</measure>
      <time_frame>From the point of randomisation until 90± 7 days following the surgical procedure.</time_frame>
      <description>Reticulocyte levels were measured at various time intervals.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>NYHA classification of cardiac function</measure>
      <time_frame>From the point of randomisation until 90± 7 days following the surgical procedure.</time_frame>
      <description>NYHA classification of cardiac function values were assessed at various time intervals.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The score measuring the quality of life after surgery.</measure>
      <time_frame>The time intervals of 30±7 days and 90±7 days were observed following the surgical procedure.</time_frame>
      <description>The findings are presented based on the EQ VAS score (0-100), which reflects the overall self-assessed health status. A higher score indicates a better health status. Additionally, the results are reported using the EQ-5D-3L Effectiveness Index (EQ-5D-3L) values (5-15), where a lower EQ-5D-3L value signifies a better state of health.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of perioperative complication within 90 days after major cardiac surgery</measure>
      <time_frame>Within 90 days after surgery</time_frame>
      <description>The potential postoperative complications within a 90-day timeframe encompass myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), serious adverse events (SAE), congestive heart failure, respiratory failure, and various infections.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The mortality rate within a 90-day postoperative period.</measure>
      <time_frame>Within 90 days after surgery</time_frame>
      <description>The mortality rate within a 90-day postoperative period.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>length of stay in hospital</measure>
      <time_frame>through study completion, an average of 14 days</time_frame>
      <description>he time period from admission to the hospital to discharge</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Length of stay in ICU</measure>
      <time_frame>through study completion, an average of 4 days</time_frame>
      <description>The time period from admission to ICU after surgery to move out from ICU to normal ward</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">480</enrollment>
    <condition>Anemia</condition>
    <condition>Iron Deficiency Anemia</condition>
    <condition>Perioperative</condition>
    <condition>Transfusion</condition>
    <condition>Cardiac Surgery</condition>
    <arm_group>
      <arm_group_label>Intervention group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Preoperative randomization was conducted, followed by a three-day regimen in the week preceding surgery, involving the administration of intravenous iron sucrose at a dosage of 200 mg per day, vitamin C at a dosage of 2 g per day, and subcutaneous administration of Human Erythropoietin Injection at a dosage of 150 IU per kilogram.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Preoperative randomization was conducted, followed by the administration of 200 ml of saline via intravenous infusion and 1 ml of saline via subcutaneous injection for three consecutive days in the week preceding the surgery.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Iron sucrose, Human Erythropoietin Injection, Vitamin C</intervention_name>
      <description>The participants were administered a combined iron supplementation regimen consisting of iron sucrose,Human Erythropoietin Injection, and vitamin C, three times throughout the preoperative week.</description>
      <arm_group_label>Intervention group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Saline</intervention_name>
      <description>The participants were administered a placebo regimen consisting of saline three times in the week preceding the surgical procedure.</description>
      <arm_group_label>Control group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Participants must be at least 18 years of age.&#xD;
  &#xD;
            2. The initial elective major cardiac surgery should encompass procedures such as&#xD;
               coronary artery bypass grafting (CABG), valve surgery, or a combination of both.&#xD;
  &#xD;
            3. Iron deficiency anemia is defined as having a ferritin level below 100 μg/L or a&#xD;
               ferritin level below 300 μg/L accompanied by a transferrin saturation below 25%.&#xD;
               Additionally, hemoglobin levels should range between 90 and 130 g/L for men or between&#xD;
               90 and 120 g/L for women.&#xD;
  &#xD;
            4. The American Society of Anesthesiologists (ASA) classification should fall within&#xD;
               Grade 1-3.&#xD;
  &#xD;
            5. Prior to participation, the patient or their legal representative must provide&#xD;
               informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Contraindications for the administration of iron sucrose, ascorbic acid, or rHuEPO.&#xD;
  &#xD;
            2. Presence of a temperature exceeding 37.5 °C or the utilization of non-prophylactic&#xD;
               antibiotics.&#xD;
  &#xD;
            3. Individuals with a weight equal to or less than 50kg.&#xD;
  &#xD;
            4. Individuals with a family history of haemochromatosis or thalassaemia, or those with a&#xD;
               transferrin saturation level exceeding 50% or a documented history of iron overload.&#xD;
  &#xD;
            5. Presence of other known haematological disorders such as folic acid or vitamin B12&#xD;
               deficiency, haemolytic anaemia, haemoglobinopathies, iron granulocytic anaemia, G6PD&#xD;
               deficiency, etc.&#xD;
  &#xD;
            6. Requirement for emergency surgical intervention.&#xD;
  &#xD;
            7. Severe hepatic or renal impairment, ALT &gt;3 times the upper limit of normal value or&#xD;
               AST &gt;3 times the upper limit of normal value, creatinine &gt;1.5 times the upper limit of&#xD;
               normal value&#xD;
  &#xD;
            8. Pregnant or lactating women&#xD;
  &#xD;
            9. history of blood transfusion, intravenous iron or ascorbic acid use within 12 weeks&#xD;
               prior to surgery&#xD;
  &#xD;
           10. Acute blood loss, gastrointestinal bleeding, etc. in the preoperative period.&#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>The Second Affiliated Hospital of Zhejiang University anesthesiology department</name>
        <address>
          <city>Hangzhou</city>
          <state>Zhejiang</state>
          <zip>310000</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Min Yan, Doctor</last_name>
        <phone>15888210247</phone>
        <email>zryanmin@zju.edu.cn</email>
      </contact>
      <investigator>
        <last_name>Min Yan, Doctor</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</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>Anemia</mesh_term>
      <mesh_term>Anemia, Iron-Deficiency</mesh_term>
      <mesh_term>Iron Deficiencies</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Epoetin Alfa</mesh_term>
      <mesh_term>Ferric Oxide, Saccharated</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>Other researchers could email us to ask the data information.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06012760
  org study id: A2023519
  nct id: NCT06012760
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Previous studies have shown that perioperative intravenous iron has a beneficial effect on
        patients with perioperative anaemia. To assess whether a combined iron supplementation
        regimen can reduce perioperative allogeneic blood transfusions in patients with iron
        deficiency anaemia undergoing major cardiac surgery under haemodynamic anaesthesia, a
        multicentre randomised clinical trial (CIPAT study) will be conducted. In the CIPAT study,
        patients undergoing elective major cardiac surgery under general anaesthesia will be randomly
        allocated to a control group and a combined iron supplementation group. Patients in the
        combined iron supplementation group will receive a combination iron supplementation regimen
        of iron sucrose in combination with Human Erythropoietin and vitamin C three times in the
        week prior to surgery, while patients in the control group will receive the same dose of
        placebo three times in the week prior to surgery. The primary endpoint is the volume of
        allogeneic erythrocyte infusion from the start of surgery to 5 days postoperatively. It is
        hypothesised that patients in the combined iron supplementation group will have fewer
        perioperative allogeneic red blood cell transfusions than those in the control group.
  The objective of this study is to examine the potential of iron sucrose in conjunction with
        human erythropoietin and vitamin C to mitigate the need for perioperative allo-erythrocyte
        infusion in patients undergoing their initial elective major cardiac surgery. This will be
        achieved by assessing outcome measures including the quantity of perioperative
        allo-erythrocyte transfusion and the alteration in perioperative haemoglobin levels.
  
        The sample size calculation for this study involved a randomised controlled trial with a
        parallel design. The intervention group consisted of individuals receiving combination
        therapy, while the control group received a placebo. The primary outcome indicator observed
        in the study population was perioperative blood transfusion. Our centre's pre-trial data
        survey indicated a perioperative blood transfusion rate of 1.8 U in the control group. It was
        hypothesized that the combination therapy would result in a reduction of blood transfusion by
        at least 0.5 U.The blood transfusion in the combination therapy group was 1.3. Setting α=0.05
        (bilaterally) with a degree of certainty=0.90. Using the bilaterally Mann-Whitney U or the
        Wilcoxon Rank-Sum test at the 0.05 level of significance (α ), when the mean difference of
        the null hypothesis was 0. Based on Poisson distribution, the sample size N1 = 188 for the
        combination treatment group and N2 = 188 cases for the placebo control group was calculated
        using PASS 21 software. Assuming a 20% loss-to-follow-up rate of study participants, a sample
        size of at least N1 = 188 ÷ 0.8 = 235 cases and N2 = 188 ÷ 0.8 = 235 cases would be required.
        In the end, 240 study subjects were included in the combination treatment group and 240 in
        the placebo control group, for a total of 480 cases.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Outcomes Assessor)
  measure: Perioperative allogeneic red blood cell transfusion volume
  time frame: From the initiation of the surgical procedure until five days post-surgery.
  description: The volume of allogeneic red blood cell transfusions during the perioperative period.
  measure: The quantity and percentage of allogeneic blood products utilized during the perioperative period.
  time frame: From the initiation of the surgical procedure until the patient's release from the hospital or the 30th day following the operation, whichever occurs earlier.
  description: This encompasses blood components such as plasma and platelets, erythrocytes.
  measure: The alterations in perioperative haemoglobin levels.
  time frame: From the point of randomisation until 90± 7 days following the surgical procedure.
  description: Haemoglobin levels were assessed at various time intervals.
  measure: The alterations in ferritin levels and serum total iron binding capacity during the perioperative period.
  time frame: From the point of randomisation until 90± 7 days following the surgical procedure.
  description: Ferritin and serum total iron binding capacity values were assessed at various time intervals.
  measure: The alterations in reticulocyte levels during the perioperative period.
  time frame: From the point of randomisation until 90± 7 days following the surgical procedure.
  description: Reticulocyte levels were measured at various time intervals.
  measure: NYHA classification of cardiac function
  time frame: From the point of randomisation until 90± 7 days following the surgical procedure.
  description: NYHA classification of cardiac function values were assessed at various time intervals.
  measure: The score measuring the quality of life after surgery.
  time frame: The time intervals of 30±7 days and 90±7 days were observed following the surgical procedure.
  description: The findings are presented based on the EQ VAS score (0-100), which reflects the overall self-assessed health status. A higher score indicates a better health status. Additionally, the results are reported using the EQ-5D-3L Effectiveness Index (EQ-5D-3L) values (5-15), where a lower EQ-5D-3L value signifies a better state of health.
  measure: Incidence of perioperative complication within 90 days after major cardiac surgery
  time frame: Within 90 days after surgery
  description: The potential postoperative complications within a 90-day timeframe encompass myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), serious adverse events (SAE), congestive heart failure, respiratory failure, and various infections.
  measure: The mortality rate within a 90-day postoperative period.
  time frame: Within 90 days after surgery
  description: The mortality rate within a 90-day postoperative period.
  measure: length of stay in hospital
  time frame: through study completion, an average of 14 days
  description: he time period from admission to the hospital to discharge
  measure: Length of stay in ICU
  time frame: through study completion, an average of 4 days
  description: The time period from admission to ICU after surgery to move out from ICU to normal ward
  arm group label: Intervention group
  arm group type: Experimental
  description: Preoperative randomization was conducted, followed by a three-day regimen in the week preceding surgery, involving the administration of intravenous iron sucrose at a dosage of 200 mg per day, vitamin C at a dosage of 2 g per day, and subcutaneous administration of Human Erythropoietin Injection at a dosage of 150 IU per kilogram.
  arm group label: Control group
  arm group type: Placebo Comparator
  description: Preoperative randomization was conducted, followed by the administration of 200 ml of saline via intravenous infusion and 1 ml of saline via subcutaneous injection for three consecutive days in the week preceding the surgery.
  intervention type: Drug
  intervention name: Iron sucrose, Human Erythropoietin Injection, Vitamin C
  description: The participants were administered a combined iron supplementation regimen consisting of iron sucrose,Human Erythropoietin Injection, and vitamin C, three times throughout the preoperative week.
  arm group label: Intervention group
  intervention type: Drug
  intervention name: Saline
  description: The participants were administered a placebo regimen consisting of saline three times in the week preceding the surgical procedure.
  arm group label: Control group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Anemia
  mesh term: Anemia, Iron-Deficiency
  mesh term: Iron Deficiencies
  mesh term: Epoetin Alfa
  mesh term: Ferric Oxide, Saccharated
  sharing ipd: Undecided
  ipd description: Other researchers could email us to ask the data information.