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Hemoglobin Optimization to Prevent Transfusion and Adverse Events in Perioperative Patients With Iron Restricted Anemia (HOPE-Hb)

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ClinicalTrials.gov Identifier: NCT03528564
Recruitment Status : Recruiting
First Posted : May 18, 2018
Last Update Posted : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
St. Michael's Hospital, Toronto

Tracking Information
First Submitted Date  ICMJE April 9, 2018
First Posted Date  ICMJE May 18, 2018
Last Update Posted Date September 19, 2019
Actual Study Start Date  ICMJE July 1, 2019
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2018)
  • Vanguard Phase (Initial 12 patients): Feasibility of using Erythropoietin + Intravenous Iron to Treat Preoperative Iron Restrictive Anemia [ Time Frame: 18 weeks from randomization ]
    The primary outcome of the vanguard phase is to determine the feasibility of using erythropoietin + intravenous iron to treat preoperative iron restrictive anemia. Feasibility will be measured according to subject enrollment rates, with adherence to the treatment schedule of >80%.
  • Full Study: Preoperative Hemoglobin Concentration [ Time Frame: 6 weeks from randomization ]
    The primary outcome of the full study is preoperative hemoglobin concentration, as measured on the day of surgery in patients with iron restricted anemia.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2018)
  • Post-Treatment Hemoglobin Concentration [ Time Frame: 12 weeks from randomization ]
    Change in post-treatment hemoglobin concentration from baseline
  • Change in Hemoglobin Concentration from Initiation of Treatment [ Time Frame: 6 weeks from randomization ]
    Rate of hemoglobin change from initiation of treatment to final preoperative hemoglobin
  • Postoperative Hemoglobin Concentration [ Time Frame: 0 weeks from surgery and 12 weeks from surgery ]
    Hemoglobin concentration on postoperative day 2 (prior to hospital discharge); and 4-6 weeks after surgery
  • Red Blood Cell Transfusions [ Time Frame: 6 weeks from surgery ]
    Rate of RBC transfusion and number of units transfused during surgery and up to 6 weeks postoperatively
  • Deep Vein Thrombosis [ Time Frame: 12 weeks from surgery ]
    Incidence of DVT up to 12 weeks postoperatively
  • Composite of Morbidity [ Time Frame: 3 months from surgery ]
    Incidence of a composite clinical outcome including death, stroke, myocardial infarction, pulmonary embolism, infection, acute kidney injury, and deep vein thrombosis from treatment to up to 3 months post surgery
  • Surgical Wound Infection [ Time Frame: 6 weeks from surgery ]
    Incidence of superficial and deep wound infection from treatment to 4-6 weeks post surgery
  • Assessment of Iron Status [ Time Frame: 6 weeks from surgery ]
    Hematological outcomes for treatment efficacy including: Hb, ferritin, hepcidin, and transferrin saturation (TSAT) pre-operatively and 4-6 weeks postoperatively
  • Digit Span Test [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of memory span
  • California Verbal Learning Test [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of word learning, recall and recognition, as well as episodic memory
  • Neuropsychological Impairment Scale [ Time Frame: 6 weeks from surgery ]
    A subjective cognitive assessment of cognitive functioning. This is a 95-item questionnaire, with all items rated on a scale from 0 (not at all) to 5 (extremely). From the 95 total items, 80 items describe neurophysiological symptoms (Global measure of impairment; GMI), 10 items describe affective disturbance, and 5 items assess test-taking attitudes. A total GMI score can range from 0-320, with higher scores indicating an increased impairment index.
  • Trail Making Test [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of processing speed
  • Digit Symbol [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of response speed, sustained attention, and visual spatial skills
  • Montreal Cognitive Assessment [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of global cognitive functioning
  • Stroop Colour and Word Test [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of processing speed
  • Wisconsin Card Sorting Test [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of a participant's ability to set-shift (display flexibility in the face of changing conditions)
  • Hospital Anxiety and Depression Scale [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of anxiety and depression levels. A total score between 0-7 indicates normal levels of depression or anxiety; a total score between 8-10 indicates borderline abnormal levels of anxiety or depression; and a total score between 11-21 indicates abnormal levels of depression or anxiety
  • Cost Analysis [ Time Frame: 12 weeks from randomization ]
    Assessment of relative cost of treatment and cost savings associated with transfusion avoidance will be assessed (see projected cost analysis; appended)
Original Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2018)
  • Post-Treatment Hemoglobin Concentration [ Time Frame: 12 weeks from randomization ]
    Change in post-treatment hemoglobin concentration from baseline
  • Change in Hemoglobin Concentration from Initiation of Treatment [ Time Frame: 6 weeks from randomization ]
    Rate of hemoglobin change from initiation of treatment to final preoperative hemoglobin
  • Postoperative Hemoglobin Concentration [ Time Frame: 0 weeks from surgery and 12 weeks from surgery ]
    Hemoglobin concentration on postoperative day 2 (prior to hospital discharge); and 4-6 weeks after surgery
  • Red Blood Cell Transfusions [ Time Frame: 6 weeks from surgery ]
    Rate of RBC transfusion and number of units transfused during surgery and up to 6 weeks postoperatively
  • Deep Vein Thrombosis [ Time Frame: 12 weeks from surgery ]
    Incidence of DVT up to 12 weeks postoperatively
  • Composite of Morbidity [ Time Frame: 3 months from surgery ]
    Incidence of a composite clinical outcome including death, stroke, myocardial infarction, pulmonary embolism, infection, acute kidney injury, and deep vein thrombosis from treatment to up to 3 months post surgery
  • Surgical Wound Infection [ Time Frame: 6 weeks from surgery ]
    Incidence of superficial and deep wound infection from treatment to 4-6 weeks post surgery
  • Assessment of Iron Status [ Time Frame: 6 weeks from surgery ]
    Hematological outcomes for treatment efficacy including: Hb, ferritin, hepcidin, and transferrin saturation (TSAT) pre-operatively and 4-6 weeks postoperatively
  • Digit Span Test [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of memory span
  • California Verbal Learning Test [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of word learning, recall and recognition, as well as episodic memory
  • Neuropsychological Impairment Scale [ Time Frame: 6 weeks from surgery ]
    A subjective cognitive assessment of cognitive functioning
  • Trail Making Test [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of processing speed
  • Digit Symbol [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of response speed, sustained attention, and visual spatial skills
  • Montreal Cognitive Assessment [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of global cognitive functioning
  • Stroop Colour and Word Test [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of processing speed
  • Wisconsin Card Sorting Test [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of a participant's ability to set-shift (display flexibility in the face of changing conditions)
  • Hospital Anxiety and Depression Scale [ Time Frame: 6 weeks from surgery ]
    Cognitive assessment of anxiety and depression levels
  • Cost Analysis [ Time Frame: 12 weeks from randomization ]
    Assessment of relative cost of treatment and cost savings associated with transfusion avoidance will be assessed (see projected cost analysis; appended)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hemoglobin Optimization to Prevent Transfusion and Adverse Events in Perioperative Patients With Iron Restricted Anemia
Official Title  ICMJE A Randomized Double-Blinded Phase II Study to Determine Treatment Protocol for Hemoglobin Optimization to Prevent Transfusion and Adverse Events in Perioperative Patients With Iron Restricted Anemia
Brief Summary The HOPE-Hb trial is a phase II study to determine the feasibility and impact of a combination treatment (intravenous iron plus erythropoietin) versus intravenous iron treatment alone on preoperative hemoglobin concentration before hip or knee arthroplasty.
Detailed Description

The purpose of the HOPE-Hb trial is to determine the feasibility and efficacy of intravenous iron plus erythropoietin versus intravenous iron alone for the treatment of iron restrictive anemia (iron deficiency anemia and anemia of chronic inflammation) prior to unilateral total hip or knee arthroplasty surgery. Half of the study population will be randomly assigned to receive intravenous iron (Venofer; iron sucrose) and Eprex (subcutaneous epoetin alfa), while the other half will be randomized to receive Venofer (intravenous iron sucrose) and placebo (subcutaneous saline). This trial will be conducted in two phases. The vanguard phase will be conducted at a single site with a primary outcome of evaluating feasibility of the study. The full study phase will be conducted at four sites with a primary outcome of determining the impact of a combination treatment (intravenous iron plus erythropoietin) versus intravenous iron treatment alone on preoperative hemoglobin concentration. This study will also examine the RBC transfusion rate and clinical outcomes such as death, stroke, myocardial infarction, pulmonary embolism, infection, kidney injury, and deep vein thrombosis as secondary outcomes.

Preoperatively, patients will be administered a total of 900mg of intravenous iron (Venofer, iron sucrose) over three visits (3-6 weeks before surgery). Then patients will be randomized to receive either two administrations of 40,000 IU of Erythropoietin (Eprex; Epoeitin alfa) or an identical placebo (saline) over two study visits (2-3 weeks before surgery). Study participants will be followed-up for 12 weeks after surgery.

Study assessments and potential adverse events reporting will be undertaken at each study visit.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Anemia, Iron Deficiency
  • Anemia of Chronic Disease
  • Hip Arthropathy
  • Knee Arthropathy
Intervention  ICMJE
  • Drug: Iron sucrose
    Intravenous iron to be administered to all patients (9 x 5 mL Single Dose Vials @ 20mg elemental iron/mL; 900 mg total)
    Other Name: Venofer
  • Drug: Epoetin Alfa
    Erythropoietin to be administered to half of study participants (40,000 IU x 1-2 subcutaneous injections)
    Other Name: Eprex
  • Drug: Placebo
    Saline to be administered to half of study participants (equal volume to Eprex x 1-2 subcutaneous injections)
    Other Name: Saline
Study Arms  ICMJE
  • Experimental: Epoetin alfa
    Preoperative treatment of anemia with iron sucrose (Venofer) plus Epoetin Alfa (Eprex)
    Interventions:
    • Drug: Iron sucrose
    • Drug: Epoetin Alfa
  • Placebo Comparator: Intravenous Iron
    Preoperative treatment of anemia with iron sucrose (Venofer) plus placebo (saline)
    Interventions:
    • Drug: Iron sucrose
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 4, 2018)
74
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 18 years of age or older at the time of consent
  • Undergoing unilateral total hip or knee arthroplasty surgery (primary)
  • Hemoglobin concentration of less than 120g/L; but greater than 60g/L

Exclusion Criteria:

  • Anemia attributed to something other than iron deficiency anemo/ACI:
  • Any other diagnosed or suspected cause of anemia (e.g. macrocytic anemia , lead toxicity, myelodysplastic syndrome)
  • Suspected of having acute blood loss due to any diagnosed condition (e.g. malignancy or gastric ulcer)
  • Mean Cell Volume (MCV) > 97fL
  • Known deficiency of vitamin B12 and/or folate
  • A known history of acquired iron overload, haemochromatosis, thalassemia or other hereditary hemoglobinopathy.
  • Received an erythropoiesis stimulating agent, IV iron therapy, or red blood cell transfusion in the previous 12 weeks (from the time of consent), or planned use prior to operation
  • Blood pressure measured at >180mmHg systolic or >100mmHg diastolic
  • Known current or prior history of liver disease or elevation of alanine transaminase (ALT), or aspartate transaminase (AST) more than two times the upper limit of normal
  • A known hypersensitivity to IV iron or erythropoietin alfa (Eprex)
  • Renal dialysis (current or historical)
  • Active infection (currently receiving antibiotics)
  • Not eligible for venous thromboembolism prophylaxis
  • Prior history of seizures or medical conditions associated with a predisposition to seizure activity such as central nervous system infections and brain metastases
  • History of thromboembolic disease or active coronary artery disease
  • Women who are pregnant or lactating (women of childbearing potential must be surgically sterile, or more than 1 year postmenopausal, or else must have a negative pregnancy test prior to randomization)
  • Recipient of an investigational drug within the past 30 days
  • Inability to speak, read, or understand the English language (required for cognitive testing)
  • Participation in a preoperative autologous blood donation program for current operation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gregory MT Hare, MD PhD 416-864-5259 hareg@smh.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03528564
Other Study ID Numbers  ICMJE HOPE-Hb
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party St. Michael's Hospital, Toronto
Study Sponsor  ICMJE St. Michael's Hospital, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gregory MT Hare, MD PhD St. Michael's Hospital; University of Toronto
PRS Account St. Michael's Hospital, Toronto
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP