Erythropoietin + Iron Therapy for Anemic Patients Undergoing Aortic Valve Replacement

Study Overview
=================
Brief Summary
-----------------
The objective of the study is to evaluate the efficacy of Erythropoietin (EPO) (+ iron) in reducing the rate of red blood cell transfusion requirements in patients with aortic stenosis undergoing transcatheter aortic valve replacement.

Detailed Description
-----------------
STUDY DESIGN Prospective randomized double blind study including patients diagnosed with severe symptomatic aortic stenosis and anemia undergoing aortic valve replacement. The patients will be identified in the cardiac surgery / aortic stenosis outpatient clinic or in the hospitalization department of the Institut Universitaire de Cardiologie et de Pneumologie de Quebec. SAMPLE SIZE 100 patients (50 patients per group).

Official Title
-----------------
Combined ErythroPoietin and Iron Therapy for AnemiC Patients With Severe Symptomatic Aortic Stenosis Undergoing Transcatheter Aortic Valve REplacement- The EPICURE Trial A Prospective Double Blind Randomized Trial

Conditions
-----------------
Anemia, Aortic Stenosis

Intervention / Treatment
-----------------
* Drug: Erythropoietin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ≥60-year old Symptomatic aortic stenosis with a clinical indication for transcatheter aortic valve replacement, regardless of simultaneous percutaneous coronary intervention Anemia defined according to the World Health Organization (WHO) definition 69: Men: Hemoglobin<130 g/L Women: <120 g/L Exclusion Criteria: Contraindication for transcatheter aortic valve replacement. Erythropoietin treatment within last 30 days before Aortic Valve Replacement Known anemia due to aplasia, other hemoglobinopathy or active bleeding requiring blood transfusion within last 30 days before Aortic Valve Replacement Ferritin>800 µg/L Uncontrolled hypertension (Blood pressure>175/95 ) Platelet count>450,000/L Recent myocardial infarction requiring percutaneous coronary intervention or disabling stroke (within the last 30 days) Dialysis patients Hemodynamic instability as defined as the need of hemodynamic support with inotropic drugs, intraortic balloon pump counter-pulsation or left ventricular assist device before index procedure Active cancer or very high risk of thromboembolic events Known allergy or hypersensitivity to intravenous iron or Erythropoietin therapy No written consent

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Erythropoietin<br>Dose: darboepoetin 0.75µg/Kg + 200mg intravenous iron sucrose Administered at days 10 (±4) and 1 (±1) before the index procedure. | Drug: Erythropoietin<br>* Combinaison drug of darboepoetin 0.75µg/Kg + 200mg intravenous iron sucrose<br>* Other names: Darboepoetin;|
| Placebo Comparator: Placebo<br>Dosage: Saline solution 0.9% Administered at days 10 (±4) and 1 (±1) before the index procedure. | Drug: Placebo<br>* Saline solution 0.9%<br>* Other names: Saline solution;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of red blood cell transfusion |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of packets of red cells |  | 30 days | 
| Hemoglobin value | Analysis g/L | One day before index procedure | 
| Hemoglobin value |  | For the duration of hospital stay, an expected average of 1 week | 
| Peak of troponin and creatinine kinase |  | For the duration of hospital stay, an expected average of 1 week | 
| Incidence of acute kidney injury | Acute kidney injury defined as >25% decrease of estimated glomerular filtration rate (eGFR) | At 48 hours following procedure | 
| Need of hemodialysis |  | For the duration of hospital stay, an expected average of 1 week | 
| Rate of new onset atrial fibrillation |  | For the duration of hospital stay, an expected average of 1 week | 
| Days of hospital stay |  | For the duration of hospital stay, an expected average of 1 week | 
| Days of intensive unit care stay |  | For the duration of hospital stay, an expected average of 1 week | 
| Mortality |  | At 30-day, 1-year | 
| Quality of life | Questionnaire, Visual scale | At 30-day, 6-month, 1-year | 
| Cost-effectiveness analysis of Erythropoietin-therapy |  | For the duration of hospital stay, an expected average of 1 week | 
| Stroke rate |  | At 30-day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anemia, Severe aortic stenosis, Red blood cell transfusion, Erythropoietin