Back to resultsHemoglobin Optimization to Prevent Transfusion and Adverse Events in Perioperative Patients With Iron Restricted Anemia (HOPE-Hb)
Primary Purpose
Anemia, Iron Deficiency, Anemia of Chronic Disease, Hip Arthropathy
Status
Terminated
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Iron sucrose
Epoetin Alfa
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Anemia, Iron Deficiency focused on measuring Preoperative Anemia, Intravenous Iron, Erythropoietin
Eligibility Criteria
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
Sites / Locations
- St. Michael's Hosptial
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Epoetin alfa
Intravenous Iron
Arm Description
Preoperative treatment of anemia with iron sucrose (Venofer) plus Epoetin Alfa (Eprex)
Preoperative treatment of anemia with iron sucrose (Venofer) plus placebo (saline)
Outcomes
Primary Outcome Measures
Vanguard Phase (Initial 12 patients): Feasibility of using Erythropoietin + Intravenous Iron to Treat Preoperative Iron Restrictive Anemia
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
The primary outcome of the full study is preoperative hemoglobin concentration, as measured on the day of surgery in patients with iron restricted anemia.
Secondary Outcome Measures
Post-Treatment Hemoglobin Concentration
Change in post-treatment hemoglobin concentration from baseline
Change in Hemoglobin Concentration from Initiation of Treatment
Rate of hemoglobin change from initiation of treatment to final preoperative hemoglobin
Postoperative Hemoglobin Concentration
Hemoglobin concentration on postoperative day 2 (prior to hospital discharge); and 4-6 weeks after surgery
Red Blood Cell Transfusions
Rate of RBC transfusion and number of units transfused during surgery and up to 6 weeks postoperatively
Deep Vein Thrombosis
Incidence of DVT up to 12 weeks postoperatively
Composite of Morbidity
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
Incidence of superficial and deep wound infection from treatment to 4-6 weeks post surgery
Assessment of Iron Status
Hematological outcomes for treatment efficacy including: Hb, ferritin, hepcidin, and transferrin saturation (TSAT) pre-operatively and 4-6 weeks postoperatively
Digit Span Test
Cognitive assessment of memory span
California Verbal Learning Test
Cognitive assessment of word learning, recall and recognition, as well as episodic memory
Neuropsychological Impairment Scale
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
Cognitive assessment of processing speed
Digit Symbol
Cognitive assessment of response speed, sustained attention, and visual spatial skills
Montreal Cognitive Assessment
Cognitive assessment of global cognitive functioning
Stroop Colour and Word Test
Cognitive assessment of processing speed
Wisconsin Card Sorting Test
Cognitive assessment of a participant's ability to set-shift (display flexibility in the face of changing conditions)
Hospital Anxiety and Depression Scale
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
Assessment of relative cost of treatment and cost savings associated with transfusion avoidance will be assessed (see projected cost analysis; appended)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03528564
Brief Title
Hemoglobin Optimization to Prevent Transfusion and Adverse Events in Perioperative Patients With Iron Restricted Anemia
Acronym
HOPE-Hb
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
The primary reasoning is that we were unable to demonstrate feasibility, prior to and because of the impact of COVID on our research programs.
Study Start Date
July 1, 2019 (Actual)
Primary Completion Date
May 31, 2021 (Actual)
Study Completion Date
May 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Unity Health Toronto
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Iron Deficiency, Anemia of Chronic Disease, Hip Arthropathy, Knee Arthropathy
Keywords
Preoperative Anemia, Intravenous Iron, Erythropoietin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Epoetin alfa
Arm Type
Experimental
Arm Description
Preoperative treatment of anemia with iron sucrose (Venofer) plus Epoetin Alfa (Eprex)
Arm Title
Intravenous Iron
Arm Type
Placebo Comparator
Arm Description
Preoperative treatment of anemia with iron sucrose (Venofer) plus placebo (saline)
Intervention Type
Drug
Intervention Name(s)
Iron sucrose
Other Intervention Name(s)
Venofer
Intervention Description
Intravenous iron to be administered to all patients (9 x 5 mL Single Dose Vials @ 20mg elemental iron/mL; 900 mg total)
Intervention Type
Drug
Intervention Name(s)
Epoetin Alfa
Other Intervention Name(s)
Eprex
Intervention Description
Erythropoietin to be administered to half of study participants (40,000 IU x 1-2 subcutaneous injections)
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline
Intervention Description
Saline to be administered to half of study participants (equal volume to Eprex x 1-2 subcutaneous injections)
Primary Outcome Measure Information:
Title
Vanguard Phase (Initial 12 patients): Feasibility of using Erythropoietin + Intravenous Iron to Treat Preoperative Iron Restrictive Anemia
Description
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%.
Time Frame
18 weeks from randomization
Title
Full Study: Preoperative Hemoglobin Concentration
Description
The primary outcome of the full study is preoperative hemoglobin concentration, as measured on the day of surgery in patients with iron restricted anemia.
Time Frame
6 weeks from randomization
Secondary Outcome Measure Information:
Title
Post-Treatment Hemoglobin Concentration
Description
Change in post-treatment hemoglobin concentration from baseline
Time Frame
12 weeks from randomization
Title
Change in Hemoglobin Concentration from Initiation of Treatment
Description
Rate of hemoglobin change from initiation of treatment to final preoperative hemoglobin
Time Frame
6 weeks from randomization
Title
Postoperative Hemoglobin Concentration
Description
Hemoglobin concentration on postoperative day 2 (prior to hospital discharge); and 4-6 weeks after surgery
Time Frame
0 weeks from surgery and 12 weeks from surgery
Title
Red Blood Cell Transfusions
Description
Rate of RBC transfusion and number of units transfused during surgery and up to 6 weeks postoperatively
Time Frame
6 weeks from surgery
Title
Deep Vein Thrombosis
Description
Incidence of DVT up to 12 weeks postoperatively
Time Frame
12 weeks from surgery
Title
Composite of Morbidity
Description
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
Time Frame
3 months from surgery
Title
Surgical Wound Infection
Description
Incidence of superficial and deep wound infection from treatment to 4-6 weeks post surgery
Time Frame
6 weeks from surgery
Title
Assessment of Iron Status
Description
Hematological outcomes for treatment efficacy including: Hb, ferritin, hepcidin, and transferrin saturation (TSAT) pre-operatively and 4-6 weeks postoperatively
Time Frame
6 weeks from surgery
Title
Digit Span Test
Description
Cognitive assessment of memory span
Time Frame
6 weeks from surgery
Title
California Verbal Learning Test
Description
Cognitive assessment of word learning, recall and recognition, as well as episodic memory
Time Frame
6 weeks from surgery
Title
Neuropsychological Impairment Scale
Description
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.
Time Frame
6 weeks from surgery
Title
Trail Making Test
Description
Cognitive assessment of processing speed
Time Frame
6 weeks from surgery
Title
Digit Symbol
Description
Cognitive assessment of response speed, sustained attention, and visual spatial skills
Time Frame
6 weeks from surgery
Title
Montreal Cognitive Assessment
Description
Cognitive assessment of global cognitive functioning
Time Frame
6 weeks from surgery
Title
Stroop Colour and Word Test
Description
Cognitive assessment of processing speed
Time Frame
6 weeks from surgery
Title
Wisconsin Card Sorting Test
Description
Cognitive assessment of a participant's ability to set-shift (display flexibility in the face of changing conditions)
Time Frame
6 weeks from surgery
Title
Hospital Anxiety and Depression Scale
Description
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
Time Frame
6 weeks from surgery
Title
Cost Analysis
Description
Assessment of relative cost of treatment and cost savings associated with transfusion avoidance will be assessed (see projected cost analysis; appended)
Time Frame
12 weeks from randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory MT Hare, MD PhD
Organizational Affiliation
St. Michael's Hospital; University of Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Michael's Hosptial
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B1W8
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Hemoglobin Optimization to Prevent Transfusion and Adverse Events in Perioperative Patients With Iron Restricted Anemia
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