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

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

Sponsors

Lead Sponsor: St. Michael's Hospital, Toronto

Source St. Michael's Hospital, Toronto
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.

Overall Status Recruiting
Start Date July 1, 2019
Completion Date December 31, 2021
Primary Completion Date June 30, 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Vanguard Phase (Initial 12 patients): Feasibility of using Erythropoietin + Intravenous Iron to Treat Preoperative Iron Restrictive Anemia 18 weeks from randomization
Full Study: Preoperative Hemoglobin Concentration 6 weeks from randomization
Secondary Outcome
Measure Time Frame
Post-Treatment Hemoglobin Concentration 12 weeks from randomization
Change in Hemoglobin Concentration from Initiation of Treatment 6 weeks from randomization
Postoperative Hemoglobin Concentration 0 weeks from surgery and 12 weeks from surgery
Red Blood Cell Transfusions 6 weeks from surgery
Deep Vein Thrombosis 12 weeks from surgery
Composite of Morbidity 3 months from surgery
Surgical Wound Infection 6 weeks from surgery
Assessment of Iron Status 6 weeks from surgery
Digit Span Test 6 weeks from surgery
California Verbal Learning Test 6 weeks from surgery
Neuropsychological Impairment Scale 6 weeks from surgery
Trail Making Test 6 weeks from surgery
Digit Symbol 6 weeks from surgery
Montreal Cognitive Assessment 6 weeks from surgery
Stroop Colour and Word Test 6 weeks from surgery
Wisconsin Card Sorting Test 6 weeks from surgery
Hospital Anxiety and Depression Scale 6 weeks from surgery
Cost Analysis 12 weeks from randomization
Enrollment 74
Condition
Intervention

Intervention Type: Drug

Intervention Name: Iron sucrose

Description: 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

Intervention Type: Drug

Intervention Name: Epoetin Alfa

Description: Erythropoietin to be administered to half of study participants (40,000 IU x 1-2 subcutaneous injections)

Arm Group Label: Epoetin alfa

Other Name: Eprex

Intervention Type: Drug

Intervention Name: Placebo

Description: Saline to be administered to half of study participants (equal volume to Eprex x 1-2 subcutaneous injections)

Arm Group Label: Intravenous Iron

Other Name: Saline

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Gregory MT Hare, MD PhD Principal Investigator St. Michael's Hospital; University of Toronto
Overall Contact

Last Name: Gregory MT Hare, MD PhD

Phone: 416-864-5259

Email: [email protected]

Location
Facility: Status: Contact: St. Michael's Hosptial Gregory MT Hare, MD, PhD 416-864-5259 [email protected]
Location Countries

Canada

Verification Date

September 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Epoetin alfa

Type: Experimental

Description: Preoperative treatment of anemia with iron sucrose (Venofer) plus Epoetin Alfa (Eprex)

Label: Intravenous Iron

Type: Placebo Comparator

Description: Preoperative treatment of anemia with iron sucrose (Venofer) plus placebo (saline)

Acronym HOPE-Hb
Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov