<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/NCT03817957</url>
  </required_header>
  <id_info>
    <org_study_id>TMP0916_03</org_study_id>
    <nct_id>NCT03817957</nct_id>
  </id_info>
  <brief_title>Postoperative i.v. Iron Substitution in Patients With Diagnosed Iron Deficiency</brief_title>
  <acronym>IDA-II</acronym>
  <official_title>Safety and Efficacy of Postoperative i.v. Iron Substitution With Polyglucoferron Compared to Ferric Carboxymaltose and Oral Iron in Patients With Diagnosed Iron Deficiency Who Develop Anaemia Peri- or Postoperatively (IDA II)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. Frank Behrens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital Frankfurt, Department of Anaesthesiology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>IRON4U</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Frankfurt Institute for Biostatistics &amp; Mathematical Modelling</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fraunhofer Institute for Molecular Biology and Applied Ecology</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>
      Iron deficiency anaemia (IDA) in postoperative patients with confirmed preoperative iron&#xD;
      deficiency (ID) in a population with planned major surgery who need fast replenishment of&#xD;
      iron as judged by the treating physician will be treated with i.v. iron using&#xD;
      Polyglucoferron, Ferric Carboxymaltose or oral iron&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, patients with confirmed and documented preoperative non-anaemic iron&#xD;
      deficiency (diagnosis up to 28 days before surgery in routine pre-surgery monitoring) who&#xD;
      develop anaemia within 12 to 72 hours after start of surgery (with additional confirmation at&#xD;
      Baseline) and for whom fast replenishment of iron stores is necessary, will be included and&#xD;
      substituted within 24h after Screening Visit/V1. Peri- or postoperative anaemia will be&#xD;
      assessed as soon as possible but earliest 12 h after surgery. For short term safety analysis&#xD;
      iron in urine will be measured in the first urine after the end of i.v. administration in the&#xD;
      first 35 patients who are eligible for analysis in each i.v. treatment group. Only those&#xD;
      patients are eligible for whom haematuria and/or proteinuria are excluded using dip stick&#xD;
      test. The Ferric Carboxymaltose treatment arm will be closed if a sufficient number of&#xD;
      patients is included for safety analysis.The study will then be continued for assessment of&#xD;
      co-primary efficacy endpoint: The effectiveness of postoperative i.v. iron substitution with&#xD;
      Polyglucoferron compared to conventional oral iron substitution with Ferrous sulfate&#xD;
      (treatment 28 - 35 days) to normalize Hb-values or to increase Hb-values by at least 1.5 g/dl&#xD;
      until visit 4 will be evaluated as well as patient related outcomes, such as the decreased&#xD;
      need for allogenic blood transfusions. In addition, the well-being of the patient will be&#xD;
      assumed to improve after treatment using the SF36 questionnaire.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 18, 2018</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 3</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>2:2:1 distribution Polyglucoferron, Ferric Carboxymaltose i.v., or oral iron substitution with Ferrous sulfate. After safety assessment of first 35 patients treated with Polyglucoferron or Ferric Carboxymaltose i.v. respectively, Ferric Carboxymaltose arm will be closed.&#xD;
Remaining patients will be distributed in an 2:1 mode to Polyglucoferron or oral iron</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients who achieve normalized Hb-levels or increased Hb of at least 1.5 g/dl</measure>
    <time_frame>Baseline to approximately 30 days post-baseline (visit 4)</time_frame>
    <description>Proportion of patients in the Polyglucoferron i.v. arm compared to oral iron substitution with Ferrous sulfate at visit 4 compared to Baseline (BL)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>pre post difference of volumen-corrected urine iron levels</measure>
    <time_frame>urine sampled prior to administration and approximately 1 to 8 hours post-baseline</time_frame>
    <description>Pre-post difference of volume-corrected urine iron levels measured before and in the first urine after the end of i.v. administration, defined as short term safety surrogate marker after administration of the i.v. treatments, compared between Polyglucoferron and Ferric Carboxymaltose (volume corrected iron urine is defined as the ratio between urine iron and urine creatinine).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with normalization of Hemoglobin (Hb) at visit 4</measure>
    <time_frame>30 days after baseline (Visit 4)</time_frame>
    <description>measurement of normalization of Hb defined in World Health Organization (WHO) classification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Hb until visit 4</measure>
    <time_frame>Baseline to 30 days after baseline (visit 4)</time_frame>
    <description>determination of levels of Hemoglobin (Hb) (comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Transferrin Saturation (TSAT) until visit 4</measure>
    <time_frame>Baseline to 30 days after baseline (visit 4)</time_frame>
    <description>determination of levels of Transferrin Saturation (TSAT) (mean values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of serum-iron until visit 4</measure>
    <time_frame>Baseline to 30 days after baseline (visit 4)</time_frame>
    <description>determination of levels of serum-iron (mean values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of serum-transferrin until visit 4</measure>
    <time_frame>Baseline to 30 days after baseline (visit 4)</time_frame>
    <description>determination of levels of serum-transferrin (mean values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of serum-ferritin until visit 4</measure>
    <time_frame>Baseline to 30 days after baseline (visit 4)</time_frame>
    <description>determination of levels of serum-ferritin (mean values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Value of serum-phosphate levels at visit 4 (i.v. groups only)</measure>
    <time_frame>baseline and 30 days after baseline (visit 4)</time_frame>
    <description>measurement of serum-phosphate levels (mean values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall tolerability and number, incidence, seriousness, severity, relationship of Adverse Events (AE) and serious adverse events (SAE) until 30 days after Investigational medicinal product (IMP) administration</measure>
    <time_frame>baseline to 30 days after last IMP administration</time_frame>
    <description>determination of number, incidence, seriousness, severity and causality of adverse events and serious adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of c-reactive protein on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of values of C reactive protein (description of changes in values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Values of ALT on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of values of ALT (description of changes in values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Values of AST on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of values of AST (description of changes in values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Values of gamma-glutamyltransferase on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of values of gamma-glutamyltransferase (description of changes in values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Values of urea nitrogen on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of values of urea nitrogen (description of changes in values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Values of serum creatinine on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of values of serum creatinine (description of changes in values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Values of white blood cells on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of values of white blood cells (description of changes in values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Values of thrombocytes on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of values of thrombocytes (description of changes in values in comparison to baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in systolic blood pressure on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of vital signs as systolic blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in body temperature on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of body temperature</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in pulse rate on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of pulse rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in diastolic blood pressure on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of vital signs as diastolic blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of general conditions on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of general condition will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of Skin on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of Skin will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of eyes on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of eyes will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of ears on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of ears will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of mouth on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of mouth will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of nose on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of nose will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of throat on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of throat will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of cardiovascular system on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of cardiovascular system will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of respiratory system on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of respiratory system,will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of abdomen on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of abdomen will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of gastrointestinal tract on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of gastrointestinal tract will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>clinical assessments of kidneys on each available visit</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of clinical assessments of kidneys will be made by investigator - changes to preceding visits and in comparison to baseline will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AEs related to injection/ infusion site reactions (i.v. treatment arms only) and hypersensitivity reactions</measure>
    <time_frame>baseline to 30 days after last IMP administration</time_frame>
    <description>Documentation of numbers of adverse events related to injection/infusion site reactions (i.v. treatment arms only) and hypersensitivity reactions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of deaths from any cause until visit 4</measure>
    <time_frame>baseline to 30 days after baseline (visit 4)</time_frame>
    <description>documentation of number of deaths</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of units of allogenic red blood cell transfusion from BL until visit 4</measure>
    <time_frame>Baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of number of units of allogenic red blood cell transfusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with need of allogenic red blood cell transfusion from BL until visit 4</measure>
    <time_frame>Baseline to 30 days after baseline (visit 4)</time_frame>
    <description>Documentation of the use of allogenic red blood cell transfusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>treatment effect on change in Quality of Life (SF36) at visit 4 compared to BL</measure>
    <time_frame>Baseline to 30 days after baseline (visit 4)</time_frame>
    <description>documentation of quality of life in the Short Form Health Survey (SF36) with 36 items relying upon patient self-reporting. It contains eight sections: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health. The SF-36 consists of eight scaled scores which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospital stay (days) until visit 4</measure>
    <time_frame>Baseline to 30 days after baseline (visit 4)</time_frame>
    <description>documentation of days in hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level ofl iron in plasma after end of iron administration (for the i.v. groups (safety analysis group) only)</measure>
    <time_frame>time points directly after administration of intravenous (i.v.) treatment (approximately 15 minutes post-baseline)</time_frame>
    <description>measurement of iron level in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of iron in plasma after urine sampling (for the i.v. groups (safety analysis group) only)</measure>
    <time_frame>time points after urine sampling (approximately 1 to 8 hours post-baseline)</time_frame>
    <description>measurement of iron level in plasma</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">407</enrollment>
  <condition>Iron Deficiency Anemia</condition>
  <arm_group>
    <arm_group_label>Polyglucoferron</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>once intravenously, dosing according to Hb-levels and body weight, 500 - 2000 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ferric Carboxymaltose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Once intravenously (a second administration is allowed), dosing according to Hb-levels and body weight (500 - 2000 mg, max. single dose of 1000 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ferrous sulfate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>capsules, orally, dosing 50 mg - 200 mg (50 mg: 1 capsule in total, 200 mg: 4 capsules in total, taken as 2 capsules twice daily), duration of treatment 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Polyglucoferron</intervention_name>
    <description>intravenous administration</description>
    <arm_group_label>Polyglucoferron</arm_group_label>
    <other_name>Feramyl</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferric carboxymaltose</intervention_name>
    <description>intravenous administration</description>
    <arm_group_label>Ferric Carboxymaltose</arm_group_label>
    <other_name>Ferinject</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferrous Sulfate</intervention_name>
    <description>oral administration</description>
    <arm_group_label>Ferrous sulfate</arm_group_label>
    <other_name>Ferro sanol duodenal</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males or female; aged ≥ 18 years&#xD;
&#xD;
          -  Patients after major surgery (e.g., orthopaedic/trauma, vascular, visceral, cardiac&#xD;
             surgery) with risk of Hb reduction and/or blood loss who develop anaemia defined as&#xD;
             haemoglobin of &lt;12 g/dL for female and &lt;13 g/dL for men within 12 to 72 h after start&#xD;
             of surgery and with confirmation at Baseline&#xD;
&#xD;
          -  Confirmed and documented preoperative iron deficiency defined as S-ferritin &lt;100 ng/mL&#xD;
             without anaemia (Hb ≥12 g/dL for female and ≥13 g/dL for male) within 28 days before&#xD;
             surgery&#xD;
&#xD;
          -  need for fast iron replenishment as judged by the treating physician&#xD;
&#xD;
          -  Written informed consent; willing/able to comply with the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy in female patients or breastfeeding women&#xD;
&#xD;
          -  Female patients not willing to use a safe method of contraception (PEARL index &lt;1) for&#xD;
             the full study period&#xD;
&#xD;
          -  Severe physical inability, e.g., American society of anesthesiologists (ASA) physical&#xD;
             status IV or V&#xD;
&#xD;
          -  Patients receiving blood transfusion 24 week prior surgery&#xD;
&#xD;
          -  Non-iron deficiency anaemia, e.g., known Vitamin B12 or folate deficiency,&#xD;
             haemoglobinopathy, or unexplained anaemia&#xD;
&#xD;
          -  Anticipated medical need for erythropoiesis-stimulating agents during the main study&#xD;
             period&#xD;
&#xD;
          -  Patients with hemodynamic instability due to any ongoing bleeding. Absence of ongoing&#xD;
             bleeding will be confirmed determined either by decision of two independent physicians&#xD;
             or by removal of drainage, whichever occurs earlier in routine care)&#xD;
&#xD;
          -  Patients with any contraindication to the investigational products, e.g.,&#xD;
&#xD;
               1. known sensitivity to iron or an ingredient of the investigational products&#xD;
&#xD;
               2. Significant history of systemic allergic reactions&#xD;
&#xD;
               3. Haemachromatosis, thalassemia or TSAT &gt;50% as indicator of iron overload&#xD;
&#xD;
               4. Acute or chronic intoxication&#xD;
&#xD;
               5. Infection (patient on non-prophylactic antibiotics)&#xD;
&#xD;
               6. Chronic liver disease and/or screening Alanine Aminotransferase (ALT) or&#xD;
                  Aspartate Aminotransferase (AST) above three times the upper limit of the normal&#xD;
                  range&#xD;
&#xD;
          -  Chronic kidney disease, defined as Glomerular Filtration Rate (GFR) &lt;30 mL/min&#xD;
&#xD;
          -  Active uncontrolled immune-mediated diseases such as rheumatoid arthritis or&#xD;
             inflammatory bowel disease&#xD;
&#xD;
          -  Primary haematologic disease&#xD;
&#xD;
          -  Drug or alcohol abuse according to WHO definition&#xD;
&#xD;
          -  Potentially unreliable patients, and those judged by the investigator to be unsuitable&#xD;
             for the study&#xD;
&#xD;
          -  Current or previous participation in another clinical trial during the last 90 days&#xD;
             before screening&#xD;
&#xD;
          -  Exclusion criteria related to Ferrous sulfate&#xD;
&#xD;
               1. according to Summary of product characteristics (SmPC)&#xD;
&#xD;
               2. hypersensitivity to any ingredient in the formulation&#xD;
&#xD;
               3. concomitant parenteral iron&#xD;
&#xD;
               4. haemochromatosis, and other iron overload syndromes&#xD;
&#xD;
          -  Exclusion criteria related to Ferric Carboxymaltose:&#xD;
&#xD;
               1. according to Summary of product characteristics (SmPC)&#xD;
&#xD;
               2. hypersensitivity to the active substance, to Ferric Carboxymaltose or any of its&#xD;
                  excipients&#xD;
&#xD;
               3. known serious hypersensitivity to other parenteral iron products&#xD;
&#xD;
               4. anaemia not attributed to iron deficiency&#xD;
&#xD;
               5. evidence of iron overload or disturbances in the utilisation of iron&#xD;
&#xD;
          -  Exclusion criteria related to Polyglucoferron&#xD;
&#xD;
               1. hypersensitivity to any ingredient in the formulation&#xD;
&#xD;
               2. known serious hypersensitivity to other parenteral iron products&#xD;
&#xD;
               3. anaemia not attributed to iron deficiency&#xD;
&#xD;
               4. evidence of iron overload or disturbances in the utilisation of iron&#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>Patrick Meybohm, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital of Goethe-University Frankfurt</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anita Bulczak-Schadendorf, Phd</last_name>
    <phone>0049696301</phone>
    <phone_ext>80221</phone_ext>
    <email>anita.bulczak-schadendorf@ime.fraunhofer.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tanja Rossmanith, Phd</last_name>
    <email>tanja.rossmanith@ime.fraunhofer.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Goethe-University</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessia</state>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Patrick Meybohm, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Kai Zacharowski, MD</last_name>
    </contact_backup>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>November 10, 2021</last_update_submitted>
  <last_update_submitted_qc>November 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Fraunhofer Institute for Molecular Biology and Applied Ecology</investigator_affiliation>
    <investigator_full_name>Dr. Frank Behrens</investigator_full_name>
    <investigator_title>Sponsor representative</investigator_title>
  </responsible_party>
  <keyword>post surgery anemia treatment,</keyword>
  <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>
  <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/NCT03817957
org study id: TMP0916_03
nct id: NCT03817957
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Iron deficiency anaemia (IDA) in postoperative patients with confirmed preoperative iron
      deficiency (ID) in a population with planned major surgery who need fast replenishment of
      iron as judged by the treating physician will be treated with i.v. iron using
      Polyglucoferron, Ferric Carboxymaltose or oral iron
In this study, patients with confirmed and documented preoperative non-anaemic iron
      deficiency (diagnosis up to 28 days before surgery in routine pre-surgery monitoring) who
      develop anaemia within 12 to 72 hours after start of surgery (with additional confirmation at
      Baseline) and for whom fast replenishment of iron stores is necessary, will be included and
      substituted within 24h after Screening Visit/V1. Peri- or postoperative anaemia will be
      assessed as soon as possible but earliest 12 h after surgery. For short term safety analysis
      iron in urine will be measured in the first urine after the end of i.v. administration in the
      first 35 patients who are eligible for analysis in each i.v. treatment group. Only those
      patients are eligible for whom haematuria and/or proteinuria are excluded using dip stick
      test. The Ferric Carboxymaltose treatment arm will be closed if a sufficient number of
      patients is included for safety analysis.The study will then be continued for assessment of
      co-primary efficacy endpoint: The effectiveness of postoperative i.v. iron substitution with
      Polyglucoferron compared to conventional oral iron substitution with Ferrous sulfate
      (treatment 28 - 35 days) to normalize Hb-values or to increase Hb-values by at least 1.5 g/dl
      until visit 4 will be evaluated as well as patient related outcomes, such as the decreased
      need for allogenic blood transfusions. In addition, the well-being of the patient will be
      assumed to improve after treatment using the SF36 questionnaire.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 2:2:1 distribution Polyglucoferron, Ferric Carboxymaltose i.v., or oral iron substitution with Ferrous sulfate. After safety assessment of first 35 patients treated with Polyglucoferron or Ferric Carboxymaltose i.v. respectively, Ferric Carboxymaltose arm will be closed.
Remaining patients will be distributed in an 2:1 mode to Polyglucoferron or oral iron
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients who achieve normalized Hb-levels or increased Hb of at least 1.5 g/dl
time frame: Baseline to approximately 30 days post-baseline (visit 4)
description: Proportion of patients in the Polyglucoferron i.v. arm compared to oral iron substitution with Ferrous sulfate at visit 4 compared to Baseline (BL)
measure: pre post difference of volumen-corrected urine iron levels
time frame: urine sampled prior to administration and approximately 1 to 8 hours post-baseline
description: Pre-post difference of volume-corrected urine iron levels measured before and in the first urine after the end of i.v. administration, defined as short term safety surrogate marker after administration of the i.v. treatments, compared between Polyglucoferron and Ferric Carboxymaltose (volume corrected iron urine is defined as the ratio between urine iron and urine creatinine).
measure: Proportion of patients with normalization of Hemoglobin (Hb) at visit 4
time frame: 30 days after baseline (Visit 4)
description: measurement of normalization of Hb defined in World Health Organization (WHO) classification
measure: Level of Hb until visit 4
time frame: Baseline to 30 days after baseline (visit 4)
description: determination of levels of Hemoglobin (Hb) (comparison to baseline)
measure: Level of Transferrin Saturation (TSAT) until visit 4
time frame: Baseline to 30 days after baseline (visit 4)
description: determination of levels of Transferrin Saturation (TSAT) (mean values in comparison to baseline)
measure: Level of serum-iron until visit 4
time frame: Baseline to 30 days after baseline (visit 4)
description: determination of levels of serum-iron (mean values in comparison to baseline)
measure: Level of serum-transferrin until visit 4
time frame: Baseline to 30 days after baseline (visit 4)
description: determination of levels of serum-transferrin (mean values in comparison to baseline)
measure: Level of serum-ferritin until visit 4
time frame: Baseline to 30 days after baseline (visit 4)
description: determination of levels of serum-ferritin (mean values in comparison to baseline)
measure: Value of serum-phosphate levels at visit 4 (i.v. groups only)
time frame: baseline and 30 days after baseline (visit 4)
description: measurement of serum-phosphate levels (mean values in comparison to baseline)
measure: Overall tolerability and number, incidence, seriousness, severity, relationship of Adverse Events (AE) and serious adverse events (SAE) until 30 days after Investigational medicinal product (IMP) administration
time frame: baseline to 30 days after last IMP administration
description: determination of number, incidence, seriousness, severity and causality of adverse events and serious adverse events
measure: Level of c-reactive protein on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of values of C reactive protein (description of changes in values in comparison to baseline)
measure: Values of ALT on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of values of ALT (description of changes in values in comparison to baseline)
measure: Values of AST on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of values of AST (description of changes in values in comparison to baseline)
measure: Values of gamma-glutamyltransferase on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of values of gamma-glutamyltransferase (description of changes in values in comparison to baseline)
measure: Values of urea nitrogen on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of values of urea nitrogen (description of changes in values in comparison to baseline)
measure: Values of serum creatinine on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of values of serum creatinine (description of changes in values in comparison to baseline)
measure: Values of white blood cells on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of values of white blood cells (description of changes in values in comparison to baseline)
measure: Values of thrombocytes on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of values of thrombocytes (description of changes in values in comparison to baseline)
measure: Changes in systolic blood pressure on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of vital signs as systolic blood pressure
measure: Changes in body temperature on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of body temperature
measure: Changes in pulse rate on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of pulse rate
measure: Changes in diastolic blood pressure on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of vital signs as diastolic blood pressure
measure: Assessment of general conditions on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of general condition will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of Skin on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of Skin will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of eyes on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of eyes will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of ears on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of ears will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of mouth on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of mouth will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of nose on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of nose will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of throat on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of throat will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of cardiovascular system on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of cardiovascular system will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of respiratory system on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of respiratory system,will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of abdomen on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of abdomen will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of gastrointestinal tract on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of gastrointestinal tract will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: clinical assessments of kidneys on each available visit
time frame: baseline to 30 days after baseline (visit 4)
description: Documentation of clinical assessments of kidneys will be made by investigator - changes to preceding visits and in comparison to baseline will be documented
measure: AEs related to injection/ infusion site reactions (i.v. treatment arms only) and hypersensitivity reactions
time frame: baseline to 30 days after last IMP administration
description: Documentation of numbers of adverse events related to injection/infusion site reactions (i.v. treatment arms only) and hypersensitivity reactions
measure: Number of deaths from any cause until visit 4
time frame: baseline to 30 days after baseline (visit 4)
description: documentation of number of deaths
measure: Proportion of units of allogenic red blood cell transfusion from BL until visit 4
time frame: Baseline to 30 days after baseline (visit 4)
description: Documentation of number of units of allogenic red blood cell transfusion
measure: Proportion of patients with need of allogenic red blood cell transfusion from BL until visit 4
time frame: Baseline to 30 days after baseline (visit 4)
description: Documentation of the use of allogenic red blood cell transfusion
measure: treatment effect on change in Quality of Life (SF36) at visit 4 compared to BL
time frame: Baseline to 30 days after baseline (visit 4)
description: documentation of quality of life in the Short Form Health Survey (SF36) with 36 items relying upon patient self-reporting. It contains eight sections: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health. The SF-36 consists of eight scaled scores which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
measure: Duration of hospital stay (days) until visit 4
time frame: Baseline to 30 days after baseline (visit 4)
description: documentation of days in hospital
measure: Level ofl iron in plasma after end of iron administration (for the i.v. groups (safety analysis group) only)
time frame: time points directly after administration of intravenous (i.v.) treatment (approximately 15 minutes post-baseline)
description: measurement of iron level in plasma
measure: Level of iron in plasma after urine sampling (for the i.v. groups (safety analysis group) only)
time frame: time points after urine sampling (approximately 1 to 8 hours post-baseline)
description: measurement of iron level in plasma
arm group label: Polyglucoferron
arm group type: Experimental
description: once intravenously, dosing according to Hb-levels and body weight, 500 - 2000 mg
arm group label: Ferric Carboxymaltose
arm group type: Active Comparator
description: Once intravenously (a second administration is allowed), dosing according to Hb-levels and body weight (500 - 2000 mg, max. single dose of 1000 mg)
arm group label: Ferrous sulfate
arm group type: Active Comparator
description: capsules, orally, dosing 50 mg - 200 mg (50 mg: 1 capsule in total, 200 mg: 4 capsules in total, taken as 2 capsules twice daily), duration of treatment 28 days
intervention type: Drug
intervention name: Polyglucoferron
description: intravenous administration
arm group label: Polyglucoferron
other name: Feramyl
intervention type: Drug
intervention name: Ferric carboxymaltose
description: intravenous administration
arm group label: Ferric Carboxymaltose
other name: Ferinject
intervention type: Drug
intervention name: Ferrous Sulfate
description: oral administration
arm group label: Ferrous sulfate
other name: Ferro sanol duodenal
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Patrick Meybohm, MD
role: Principal Investigator
affiliation: University Hospital of Goethe-University Frankfurt
last name: Anita Bulczak-Schadendorf, Phd
phone: 0049696301
phone ext: 80221
email: anita.bulczak-schadendorf@ime.fraunhofer.de
last name: Tanja Rossmanith, Phd
email: tanja.rossmanith@ime.fraunhofer.de
facility: 
status: Recruiting
contact: 
contact backup: 
country: Germany
responsible party type: Sponsor-Investigator
investigator affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology
investigator full name: Dr. Frank Behrens
investigator title: Sponsor representative
mesh term: Anemia
mesh term: Anemia, Iron-Deficiency
mesh term: Iron Deficiencies
sharing ipd: No