<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/NCT03769441</url>
  </required_header>
  <id_info>
    <org_study_id>201800450</org_study_id>
    <nct_id>NCT03769441</nct_id>
  </id_info>
  <brief_title>Effect of Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation</brief_title>
  <acronym>EFFECT-KTx</acronym>
  <official_title>Effect of Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation: a Multicenter Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dutch Kidney Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vifor Fresenius Medical Care Renal Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Medical Center Groningen</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 is common in kidney transplant recipients and is associated with impaired&#xD;
      exercise tolerance and an unfavourable prognosis.&#xD;
&#xD;
      This multicentre double-blind, placebo-controlled randomized controlled clinical trial will&#xD;
      allow the investigators to analyse the effects of intravenous iron correction with&#xD;
      ferric(III) carboxymaltose on exercise tolerance and other parameters, in comparison to a&#xD;
      placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Iron deficiency is common in kidney transplant recipients. The presence of iron&#xD;
      deficiency is associated with an unfavourable prognosis in these patients. In patients with&#xD;
      heart failure and iron deficiency, treatment with intravenous iron improved exercise capacity&#xD;
      and quality of life. Whether such beneficial effects may also occur in kidney transplant&#xD;
      recipients is unknown.&#xD;
&#xD;
      Objective: Our main objective is to address whether correction of iron deficiency with&#xD;
      ferric(III) carboxymaltose improves exercise tolerance and quality of life in iron-deficient&#xD;
      kidney-transplant recipients.&#xD;
&#xD;
      Study design: A multicentre double-blind, placebo-controlled randomized controlled clinical&#xD;
      trial will be performed to compare the effects of ferric(III) carboxymaltose with placebo.&#xD;
&#xD;
      Study population: 158 iron-deficient kidney transplant recipients. The intervention arm will&#xD;
      receive 10 mL of ferric(III) carboxymaltose (50 mg Fe3/mL, intravenously) every six weeks,&#xD;
      with a total of four dosages. The control arm receives an intravenous placebo solution&#xD;
      (saline).&#xD;
&#xD;
      Main study parameters/endpoints: The primary endpoint is the distance walked in six minutes,&#xD;
      as quantified by the six-minute-walking-test at the end of follow-up.&#xD;
&#xD;
      The investigators expect that iron-deficient kidney transplant recipients will benefit from&#xD;
      ferric(III) carboxymaltose treatment as a result of an improvement in exercise tolerance and&#xD;
      general wellbeing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 2, 2019</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>The study is designed as a 24 week, multicentre, randomized placebo-controlled clinical trial with two parallel arms to investigate the effect of ferric(III) carboxymaltose on exercise tolerance, cardiac function, skeletal muscle function, quality of life, the gut microbiota and on the immune system, to be performed at the University Medical Center Groningen (UMCG) and the Erasmus MC, University Medical Center Rotterdam.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>All participants, care providers and researchers will be blinded, except for the nurse who will administer the medication.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Exercise tolerance</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in exercise tolerance quantified by the six-minute walk test (6MWT)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin level</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in hemoglobin level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Iron status</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in iron parameters (plasma iron, ferritin, transferrin saturation)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac function</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in cardiac structure, function and strain, analysed with a transthoracic echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle strength 1</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in muscle strength measured by the 'Five-Times-Sit-to-Stand-test (FTSTS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle strength 2</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in muscle strength measured by the timed-up-and-Go test (TUG)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle strength 3</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in muscle strength measured by handgrip dynamometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle mass</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in muscle mass assessed using 24-hour urinary creatinine excretion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phosphate level</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in phosphate level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calcium level</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in calcium level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vitamin D status</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in vitamin D level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parathyroid hormone</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in parathyroid hormone level level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FGF23</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in FGF23 level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intestinal microbiota</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in intestinal microbiota</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of any infection</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in incidence of infections</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of hospitalisation</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in incidence of hospitalisation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of cardiac events</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in incidence of cardiac events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of graft failure</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in incidence of graft failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lymphocyte production of cytokines</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in lymphocyte cytokine espression (measured with facs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lymphocyte production of immunoglobulins</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in lymphocyte IgG production (measured with ELISA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lymphocyte proliferation rate</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in lymphocyte proliferation rate (assessed with FACS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>B-lymphocyte differentiation rate</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in B-lymphocyte plasma cell formation (assessed with Facs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive performance (memory span)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in cognitive performance quantified with neuropsychological testing (Digit Span Forward Test, minimum value 0, maximum value 9, a higher score means a better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive performance (verbal memory)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in cognitive performance quantified with neuropsychological testing (15 word test, minimum value 0, maximum value 75, a higher score means a better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive performance (semantic memory)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in cognitive performance quantified with neuropsychological testing (Word Fluency Test, minimum value 0, no maximum value, a higher score means a better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive performance (processing speed)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in cognitive performance quantified with neuropsychological testing (symbol digit modalities test, minimum value 0, maximum value 110, a higher score means a better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive performance (visuomotor and mental speed)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in cognitive performance quantified with neuropsychological testing (Trail Making Test A, minimum value 1, no maximum value, a lower score means a better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive performance (cognitive flexibility)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in cognitive performance quantified with neuropsychological testing (Trail Making Test B, minimum value 1, no maximum value, a lower score means a better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive performance (executive control)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in cognitive performance quantified with neuropsychological testing (Controlled Oral Word Association Test, minimum score 1, no maximum score, a higher score means a better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive performance (working memory)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in cognitive performance quantified with neuropsychological testing (Digit Span Backward, minimum score 0, maximum score 8, a higher score means a better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma creatinine</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in plasma creatinine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (health)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in quality of life quantified with SF36 questionnaire. A higher score means a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (subjective fatigue)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in quality of life quantified with the Dutch Checklist individual Strength). A higher score means worse fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (long-lasting fatigue)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in quality of life quantified with the Dutch Multifactor Fatigue Scale). A higher score means worse fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (overall)</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in quality of life quantified with EuroQol-5D-5L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination IgG response</measure>
    <time_frame>12 months</time_frame>
    <description>The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific antibody titre after vaccination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination T-lymphocyte response</measure>
    <time_frame>12 months</time_frame>
    <description>The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specif T-lymphocyte response after vaccination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastro-intestinal symptoms</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in gastro-intestinal symptoms assessed with the gastrointestinal symptom rating scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hepatic injury</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in plasma hepatic enzyme levels (aspartate transaminase and alanine transaminase)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Restless legs</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in prevalence of restless legs symptoms before and after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney graft rejection and injury</measure>
    <time_frame>24 weeks</time_frame>
    <description>The between-group difference in change in urine kidney injury marker levels</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">158</enrollment>
  <condition>Iron-deficiency</condition>
  <condition>Transplant-Related Disorder</condition>
  <arm_group>
    <arm_group_label>Ferric(III) carboxymaltose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The intervention group will be treated with four dosages of 500 mg iron in the form of 10 mL ferric(III) carboxymaltose dissolved in 240 mL of NaCl 0.9%, with interval periods of six weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo-controlled group will receive four dosages of 250 mL of NaCl 0.9% solution with interval periods of six weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferric carboxymaltose</intervention_name>
    <description>Four intravenous dosages of ferric(III) carboxymaltose</description>
    <arm_group_label>Ferric(III) carboxymaltose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium chloride</intervention_name>
    <description>Four intravenous dosages of sodiumchloride</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Kidney transplant recipient&#xD;
&#xD;
          -  Iron deficiency, defined by a ferritin level of ≤100 ug/L, or 100-299 ug/L combined&#xD;
             with a transferrin saturation of ≤20%&#xD;
&#xD;
          -  At least six months after transplantation at baseline&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Ability to comply with the study protocol&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Intolerance to any intravenous iron solution&#xD;
&#xD;
          -  Severe anemia (Hb &lt;10.5 g/dL, &lt;6.5 mmol/L), microcytic anemia (MCV &lt;80 fl) or&#xD;
             progressive anemia (˃3.2 g/dL per month decline for two months or more)&#xD;
&#xD;
          -  A positive feces occult blood test or otherwise demonstrated gastrointestinal, or&#xD;
             urogenital, blood loss&#xD;
&#xD;
          -  Blood transfusion in the past six weeks&#xD;
&#xD;
          -  Polycythemia (Hb &gt;15.3 g/dL, 9.5 mmol/L)&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) of ≤ 30 ml/min per 1.73 m2&#xD;
&#xD;
          -  History of haemochromatosis&#xD;
&#xD;
          -  Unstable angina or myocardial infarction during the previous month&#xD;
&#xD;
          -  Disability to walk&#xD;
&#xD;
          -  Severe hypophosphatemia in the month before baseline (serum phosphate &lt;0.35 mmol/L)&#xD;
&#xD;
          -  Pregnancy or inability to take adequate contraceptive measures when at childbearing&#xD;
             age (women)&#xD;
&#xD;
          -  Any signs of an active systemic infection&#xD;
&#xD;
          -  Participation in another interventional study&#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>Martin de Borst, MD/PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Center Groningen</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anna-Sophie Vinke, MD</last_name>
    <phone>0031503611697</phone>
    <email>j.s.j.vinke@umcg.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Medical Center Groningen</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna-Sophie Vinke, MD</last_name>
      <phone>00315011697</phone>
      <email>j.s.j.vinke@umcg.nl</email>
    </contact>
    <investigator>
      <last_name>Martin de Borst, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Medical Center Utrecht</name>
      <address>
        <city>Utrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Arjan D van Zuilen, MD, PhD</last_name>
      <email>a.vanzuilen@umcutrecht.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>January 14, 2023</last_update_submitted>
  <last_update_submitted_qc>January 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Center Groningen</investigator_affiliation>
    <investigator_full_name>Martin H. de Borst</investigator_full_name>
    <investigator_title>Principal Investigator, Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Renal Transplantation</keyword>
  <keyword>Kidney Transplantation</keyword>
  <keyword>Iron Deficiency</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Iron-Deficiency</mesh_term>
    <mesh_term>Iron Deficiencies</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>To protect participant privacy, public access to the dataset or individual participant data will not be provided. However, after deidentification of these data and after publication of the main results, requests for the re-use of all pseudo-anonymised individual participant data by researchers who provide a methodologically sound proposal for a secondary analysis or meta-analysis will be evaluated by the Principal Investigator. Data may be shared if the research question falls within the scope of the informed consent. Proposals should be directed to m.h.de.borst@umcg.nl and requestors will need to sign a data access agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>The study protocol, including a statistical data analysis plan, will be published in a peer-reviewed journal.</ipd_time_frame>
  </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/NCT03769441
org study id: 201800450
nct id: NCT03769441
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Iron deficiency is common in kidney transplant recipients and is associated with impaired
      exercise tolerance and an unfavourable prognosis.

      This multicentre double-blind, placebo-controlled randomized controlled clinical trial will
      allow the investigators to analyse the effects of intravenous iron correction with
      ferric(III) carboxymaltose on exercise tolerance and other parameters, in comparison to a
      placebo.
Rationale: Iron deficiency is common in kidney transplant recipients. The presence of iron
      deficiency is associated with an unfavourable prognosis in these patients. In patients with
      heart failure and iron deficiency, treatment with intravenous iron improved exercise capacity
      and quality of life. Whether such beneficial effects may also occur in kidney transplant
      recipients is unknown.

      Objective: Our main objective is to address whether correction of iron deficiency with
      ferric(III) carboxymaltose improves exercise tolerance and quality of life in iron-deficient
      kidney-transplant recipients.

      Study design: A multicentre double-blind, placebo-controlled randomized controlled clinical
      trial will be performed to compare the effects of ferric(III) carboxymaltose with placebo.

      Study population: 158 iron-deficient kidney transplant recipients. The intervention arm will
      receive 10 mL of ferric(III) carboxymaltose (50 mg Fe3/mL, intravenously) every six weeks,
      with a total of four dosages. The control arm receives an intravenous placebo solution
      (saline).

      Main study parameters/endpoints: The primary endpoint is the distance walked in six minutes,
      as quantified by the six-minute-walking-test at the end of follow-up.

      The investigators expect that iron-deficient kidney transplant recipients will benefit from
      ferric(III) carboxymaltose treatment as a result of an improvement in exercise tolerance and
      general wellbeing.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study is designed as a 24 week, multicentre, randomized placebo-controlled clinical trial with two parallel arms to investigate the effect of ferric(III) carboxymaltose on exercise tolerance, cardiac function, skeletal muscle function, quality of life, the gut microbiota and on the immune system, to be performed at the University Medical Center Groningen (UMCG) and the Erasmus MC, University Medical Center Rotterdam.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: All participants, care providers and researchers will be blinded, except for the nurse who will administer the medication.
measure: Exercise tolerance
time frame: 24 weeks
description: The between-group difference in change in exercise tolerance quantified by the six-minute walk test (6MWT)
measure: Hemoglobin level
time frame: 24 weeks
description: The between-group difference in change in hemoglobin level
measure: Iron status
time frame: 24 weeks
description: The between-group difference in change in iron parameters (plasma iron, ferritin, transferrin saturation)
measure: Cardiac function
time frame: 24 weeks
description: The between-group difference in change in cardiac structure, function and strain, analysed with a transthoracic echocardiography
measure: Muscle strength 1
time frame: 24 weeks
description: The between-group difference in change in muscle strength measured by the 'Five-Times-Sit-to-Stand-test (FTSTS)
measure: Muscle strength 2
time frame: 24 weeks
description: The between-group difference in change in muscle strength measured by the timed-up-and-Go test (TUG)
measure: Muscle strength 3
time frame: 24 weeks
description: The between-group difference in change in muscle strength measured by handgrip dynamometry
measure: Muscle mass
time frame: 24 weeks
description: The between-group difference in change in muscle mass assessed using 24-hour urinary creatinine excretion
measure: Phosphate level
time frame: 24 weeks
description: The between-group difference in change in phosphate level
measure: Calcium level
time frame: 24 weeks
description: The between-group difference in change in calcium level
measure: Vitamin D status
time frame: 24 weeks
description: The between-group difference in change in vitamin D level
measure: Parathyroid hormone
time frame: 24 weeks
description: The between-group difference in change in parathyroid hormone level level
measure: FGF23
time frame: 24 weeks
description: The between-group difference in change in FGF23 level
measure: Intestinal microbiota
time frame: 24 weeks
description: The between-group difference in change in intestinal microbiota
measure: Incidence of any infection
time frame: 24 weeks
description: The between-group difference in incidence of infections
measure: Incidence of hospitalisation
time frame: 24 weeks
description: The between-group difference in incidence of hospitalisation
measure: Incidence of cardiac events
time frame: 24 weeks
description: The between-group difference in incidence of cardiac events
measure: Incidence of graft failure
time frame: 24 weeks
description: The between-group difference in incidence of graft failure
measure: Lymphocyte production of cytokines
time frame: 24 weeks
description: The between-group difference in lymphocyte cytokine espression (measured with facs)
measure: Lymphocyte production of immunoglobulins
time frame: 24 weeks
description: The between-group difference in lymphocyte IgG production (measured with ELISA)
measure: Lymphocyte proliferation rate
time frame: 24 weeks
description: The between-group difference in lymphocyte proliferation rate (assessed with FACS)
measure: B-lymphocyte differentiation rate
time frame: 24 weeks
description: The between-group difference in B-lymphocyte plasma cell formation (assessed with Facs)
measure: Cognitive performance (memory span)
time frame: 24 weeks
description: The between-group difference in change in cognitive performance quantified with neuropsychological testing (Digit Span Forward Test, minimum value 0, maximum value 9, a higher score means a better outcome)
measure: Cognitive performance (verbal memory)
time frame: 24 weeks
description: The between-group difference in change in cognitive performance quantified with neuropsychological testing (15 word test, minimum value 0, maximum value 75, a higher score means a better outcome)
measure: Cognitive performance (semantic memory)
time frame: 24 weeks
description: The between-group difference in change in cognitive performance quantified with neuropsychological testing (Word Fluency Test, minimum value 0, no maximum value, a higher score means a better outcome)
measure: Cognitive performance (processing speed)
time frame: 24 weeks
description: The between-group difference in change in cognitive performance quantified with neuropsychological testing (symbol digit modalities test, minimum value 0, maximum value 110, a higher score means a better outcome)
measure: Cognitive performance (visuomotor and mental speed)
time frame: 24 weeks
description: The between-group difference in change in cognitive performance quantified with neuropsychological testing (Trail Making Test A, minimum value 1, no maximum value, a lower score means a better outcome)
measure: Cognitive performance (cognitive flexibility)
time frame: 24 weeks
description: The between-group difference in change in cognitive performance quantified with neuropsychological testing (Trail Making Test B, minimum value 1, no maximum value, a lower score means a better outcome)
measure: Cognitive performance (executive control)
time frame: 24 weeks
description: The between-group difference in change in cognitive performance quantified with neuropsychological testing (Controlled Oral Word Association Test, minimum score 1, no maximum score, a higher score means a better outcome)
measure: Cognitive performance (working memory)
time frame: 24 weeks
description: The between-group difference in change in cognitive performance quantified with neuropsychological testing (Digit Span Backward, minimum score 0, maximum score 8, a higher score means a better outcome)
measure: Plasma creatinine
time frame: 24 weeks
description: The between-group difference in change in plasma creatinine
measure: Quality of Life (health)
time frame: 24 weeks
description: The between-group difference in change in quality of life quantified with SF36 questionnaire. A higher score means a better outcome.
measure: Quality of Life (subjective fatigue)
time frame: 24 weeks
description: The between-group difference in change in quality of life quantified with the Dutch Checklist individual Strength). A higher score means worse fatigue.
measure: Quality of Life (long-lasting fatigue)
time frame: 24 weeks
description: The between-group difference in change in quality of life quantified with the Dutch Multifactor Fatigue Scale). A higher score means worse fatigue.
measure: Quality of Life (overall)
time frame: 24 weeks
description: The between-group difference in change in quality of life quantified with EuroQol-5D-5L
measure: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination IgG response
time frame: 12 months
description: The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific antibody titre after vaccination.
measure: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination T-lymphocyte response
time frame: 12 months
description: The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specif T-lymphocyte response after vaccination.
measure: Gastro-intestinal symptoms
time frame: 24 weeks
description: The between-group difference in change in gastro-intestinal symptoms assessed with the gastrointestinal symptom rating scale.
measure: Hepatic injury
time frame: 24 weeks
description: The between-group difference in change in plasma hepatic enzyme levels (aspartate transaminase and alanine transaminase)
measure: Restless legs
time frame: 24 weeks
description: The between-group difference in prevalence of restless legs symptoms before and after treatment
measure: Kidney graft rejection and injury
time frame: 24 weeks
description: The between-group difference in change in urine kidney injury marker levels
arm group label: Ferric(III) carboxymaltose
arm group type: Active Comparator
description: The intervention group will be treated with four dosages of 500 mg iron in the form of 10 mL ferric(III) carboxymaltose dissolved in 240 mL of NaCl 0.9%, with interval periods of six weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: The placebo-controlled group will receive four dosages of 250 mL of NaCl 0.9% solution with interval periods of six weeks.
intervention type: Drug
intervention name: Ferric carboxymaltose
description: Four intravenous dosages of ferric(III) carboxymaltose
arm group label: Ferric(III) carboxymaltose
intervention type: Drug
intervention name: Sodium chloride
description: Four intravenous dosages of sodiumchloride
arm group label: Placebo
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Martin de Borst, MD/PhD
role: Principal Investigator
affiliation: University Medical Center Groningen
last name: Anna-Sophie Vinke, MD
phone: 0031503611697
email: j.s.j.vinke@umcg.nl
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: University Medical Center Groningen
investigator full name: Martin H. de Borst
investigator title: Principal Investigator, Clinical Professor
mesh term: Anemia, Iron-Deficiency
mesh term: Iron Deficiencies
sharing ipd: Yes
ipd description: To protect participant privacy, public access to the dataset or individual participant data will not be provided. However, after deidentification of these data and after publication of the main results, requests for the re-use of all pseudo-anonymised individual participant data by researchers who provide a methodologically sound proposal for a secondary analysis or meta-analysis will be evaluated by the Principal Investigator. Data may be shared if the research question falls within the scope of the informed consent. Proposals should be directed to m.h.de.borst@umcg.nl and requestors will need to sign a data access agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: The study protocol, including a statistical data analysis plan, will be published in a peer-reviewed journal.