Clinical trial NCT03528564: Hemoglobin Optimization to Prevent Transfusion and Adverse Events in Perioperative Patients With Iron Restricted Anemia
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Anemia, Iron Deficiency
Anemia of Chronic Disease
Hip Arthropathy
Knee Arthropathy
Keywords: Preoperative Anemia
Intravenous Iron
Erythropoietin
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
First posted: 2018-05-18
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Vanguard Phase (Initial 12 patients): Feasibility of using Erythropoietin + Intravenous Iron to Treat Preoperative Iron Restrictive Anemia
timeFrame: 18 weeks from randomization
measure: Full Study: Preoperative Hemoglobin Concentration
timeFrame: 6 weeks from randomization
Secondary outcomes:
measure: Post-Treatment Hemoglobin Concentration
timeFrame: 12 weeks from randomization
measure: Change in Hemoglobin Concentration from Initiation of Treatment
timeFrame: 6 weeks from randomization
measure: Postoperative Hemoglobin Concentration
timeFrame: 0 weeks from surgery and 12 weeks from surgery
measure: Red Blood Cell Transfusions
timeFrame: 6 weeks from surgery
measure: Deep Vein Thrombosis
timeFrame: 12 weeks from surgery
measure: Composite of Morbidity
timeFrame: 3 months from surgery
measure: Surgical Wound Infection
timeFrame: 6 weeks from surgery
measure: Assessment of Iron Status
timeFrame: 6 weeks from surgery
measure: Digit Span Test
timeFrame: 6 weeks from surgery
measure: California Verbal Learning Test
timeFrame: 6 weeks from surgery
measure: Neuropsychological Impairment Scale
timeFrame: 6 weeks from surgery
measure: Trail Making Test
timeFrame: 6 weeks from surgery
measure: Digit Symbol
timeFrame: 6 weeks from surgery
measure: Montreal Cognitive Assessment
timeFrame: 6 weeks from surgery
measure: Stroop Colour and Word Test
timeFrame: 6 weeks from surgery
measure: Wisconsin Card Sorting Test
timeFrame: 6 weeks from surgery
measure: Hospital Anxiety and Depression Scale
timeFrame: 6 weeks from surgery
measure: Cost Analysis
timeFrame: 12 weeks from randomization
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hosptial
state: Ontario
Study officials:
affiliation: St. Michael's Hospital; University of Toronto
name: Gregory MT Hare, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: