Hemoglobin Optimization to Prevent Transfusion and Adverse Events in Perioperative Patients With Iron Restricted Anemia

Knee Arthropathy Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03528564
• Other study ID #: HOPE-Hb
• Status: Terminated
• Phase: Phase 2
• Start date: July 1, 2019
• Est. completion date: May 31, 2021

Study information

• Verified date: June 2021
• Source: Unity Health Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: May 31, 2021
• Est. primary completion date: May 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Anemia of Chronic Disease
• Anemia, Iron Deficiency
• Anemia, Iron-Deficiency
• Chronic Disease
• Hip Arthropathy
• Joint Diseases
• Knee Arthropathy

Intervention

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)
• Epoetin Alfa
Erythropoietin to be administered to half of study participants (40,000 IU x 1-2 subcutaneous injections)
• Placebo
Saline to be administered to half of study participants (equal volume to Eprex x 1-2 subcutaneous injections)

Locations

Country	Name	City	State
Canada	St. Michael's Hosptial	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Unity Health Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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%.	18 weeks from randomization
Primary	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.	6 weeks from randomization
Secondary	Post-Treatment Hemoglobin Concentration	Change in post-treatment hemoglobin concentration from baseline	12 weeks from randomization
Secondary	Change in Hemoglobin Concentration from Initiation of Treatment	Rate of hemoglobin change from initiation of treatment to final preoperative hemoglobin	6 weeks from randomization
Secondary	Postoperative Hemoglobin Concentration	Hemoglobin concentration on postoperative day 2 (prior to hospital discharge); and 4-6 weeks after surgery	0 weeks from surgery and 12 weeks from surgery
Secondary	Red Blood Cell Transfusions	Rate of RBC transfusion and number of units transfused during surgery and up to 6 weeks postoperatively	6 weeks from surgery
Secondary	Deep Vein Thrombosis	Incidence of DVT up to 12 weeks postoperatively	12 weeks from surgery
Secondary	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	3 months from surgery
Secondary	Surgical Wound Infection	Incidence of superficial and deep wound infection from treatment to 4-6 weeks post surgery	6 weeks from surgery
Secondary	Assessment of Iron Status	Hematological outcomes for treatment efficacy including: Hb, ferritin, hepcidin, and transferrin saturation (TSAT) pre-operatively and 4-6 weeks postoperatively	6 weeks from surgery
Secondary	Digit Span Test	Cognitive assessment of memory span	6 weeks from surgery
Secondary	California Verbal Learning Test	Cognitive assessment of word learning, recall and recognition, as well as episodic memory	6 weeks from surgery
Secondary	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.	6 weeks from surgery
Secondary	Trail Making Test	Cognitive assessment of processing speed	6 weeks from surgery
Secondary	Digit Symbol	Cognitive assessment of response speed, sustained attention, and visual spatial skills	6 weeks from surgery
Secondary	Montreal Cognitive Assessment	Cognitive assessment of global cognitive functioning	6 weeks from surgery
Secondary	Stroop Colour and Word Test	Cognitive assessment of processing speed	6 weeks from surgery
Secondary	Wisconsin Card Sorting Test	Cognitive assessment of a participant's ability to set-shift (display flexibility in the face of changing conditions)	6 weeks from surgery
Secondary	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	6 weeks from surgery
Secondary	Cost Analysis	Assessment of relative cost of treatment and cost savings associated with transfusion avoidance will be assessed (see projected cost analysis; appended)	12 weeks from randomization