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
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Unity Health Toronto
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Vanguard Phase (Initial 12 patients): Feasibility of using Erythropoietin + Intravenous Iron to Treat Preoperative Iron Restrictive Anemia
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Intravenous Iron
Preoperative treatment of anemia with iron sucrose (Venofer) plus placebo (saline)
Intervention: Placebo (Drug)
Intravenous Iron
Preoperative treatment of anemia with iron sucrose (Venofer) plus placebo (saline)
Intervention: Iron sucrose (Drug)
Epoetin alfa
Preoperative treatment of anemia with iron sucrose (Venofer) plus Epoetin Alfa (Eprex)
Intervention: Epoetin Alfa (Drug)
Epoetin alfa
Preoperative treatment of anemia with iron sucrose (Venofer) plus Epoetin Alfa (Eprex)
Intervention: Iron sucrose (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Deep Vein Thrombosis(12 weeks from surgery)
- Postoperative Hemoglobin Concentration(0 weeks from surgery and 12 weeks from surgery)
- Change in Hemoglobin Concentration from Initiation of Treatment(6 weeks from randomization)
- Digit Span Test(6 weeks from surgery)
- California Verbal Learning Test(6 weeks from surgery)
- Stroop Colour and Word Test(6 weeks from surgery)
- Surgical Wound Infection(6 weeks from surgery)
- Cost Analysis(12 weeks from randomization)
- Post-Treatment Hemoglobin Concentration(12 weeks from randomization)
- Assessment of Iron Status(6 weeks from surgery)
- Neuropsychological Impairment Scale(6 weeks from surgery)
- Red Blood Cell Transfusions(6 weeks from surgery)
- Composite of Morbidity(3 months from surgery)
- Trail Making Test(6 weeks from surgery)
- Digit Symbol(6 weeks from surgery)
- Montreal Cognitive Assessment(6 weeks from surgery)
- Hospital Anxiety and Depression Scale(6 weeks from surgery)
- Wisconsin Card Sorting Test(6 weeks from surgery)