Erythropoietin + Iron Therapy for Anemic Patients Undergoing Aortic Valve Replacement

Anemia Clinical Trial

— EPICURE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02390102
• Other study ID #: EPICURE
• Secondary ID: CER-20809
• Status: Completed
• Phase: Phase 3
• Start date: June 2012
• Est. completion date: June 2016

Study information

• Verified date: July 2018
• Source: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: June 2016
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

1. Patients =60-year old

2. Symptomatic aortic stenosis with a clinical indication for transcatheter aortic valve replacement, regardless of simultaneous percutaneous coronary intervention

3. Anemia defined according to the World Health Organization (WHO) definition 69:

1. Men: Hemoglobin<130 g/L

2. Women: <120 g/L

Exclusion Criteria:

1. Contraindication for transcatheter aortic valve replacement.

2. Erythropoietin treatment within last 30 days before Aortic Valve Replacement

3. Known anemia due to aplasia, other hemoglobinopathy or active bleeding requiring blood transfusion within last 30 days before Aortic Valve Replacement

4. Ferritin>800 µg/L

5. Uncontrolled hypertension (Blood pressure>175/95 )

6. Platelet count>450,000/L

7. Recent myocardial infarction requiring percutaneous coronary intervention or disabling stroke (within the last 30 days)

8. Dialysis patients

9. 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

10. Active cancer or very high risk of thromboembolic events

11. Known allergy or hypersensitivity to intravenous iron or Erythropoietin therapy

12. No written consent

Related Conditions & MeSH terms

• Anemia
• Aortic Stenosis
• Aortic Valve Stenosis
• Constriction, Pathologic

Intervention

Drug:
• Erythropoietin
Combinaison drug of darboepoetin 0.75µg/Kg + 200mg intravenous iron sucrose
• Placebo
Saline solution 0.9%

Locations

Country	Name	City	State
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Country where clinical trial is conducted

Canada, 

References & Publications (19)

Bagur R, Webb JG, Nietlispach F, Dumont E, De Larochellière R, Doyle D, Masson JB, Gutiérrez MJ, Clavel MA, Bertrand OF, Pibarot P, Rodés-Cabau J. Acute kidney injury following transcatheter aortic valve implantation: predictive factors, prognostic value, and comparison with surgical aortic valve replacement. Eur Heart J. 2010 Apr;31(7):865-74. doi: 10.1093/eurheartj/ehp552. Epub 2009 Dec 27. — View Citation

Bucerius J, Gummert JF, Borger MA, Walther T, Doll N, Onnasch JF, Metz S, Falk V, Mohr FW. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg. 2003 Feb;75(2):472-8. — View Citation

Gombotz H. Subcutaneous epoetin alfa as an adjunct to autologous blood donation before elective coronary artery bypass graft surgery. Semin Hematol. 1996 Apr;33(2 Suppl 2):69-70; discussion 71-2. — View Citation

Karkouti K, Djaiani G, Borger MA, Beattie WS, Fedorko L, Wijeysundera D, Ivanov J, Karski J. Low hematocrit during cardiopulmonary bypass is associated with increased risk of perioperative stroke in cardiac surgery. Ann Thorac Surg. 2005 Oct;80(4):1381-7. — View Citation

Karkouti K, Wijeysundera DN, Beattie WS; Reducing Bleeding in Cardiac Surgery (RBC) Investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study. Circulation. 2008 Jan 29;117(4):478-84. doi: 10.1161/CIRCULATIONAHA.107.718353. Epub 2008 Jan 2. — View Citation

Kiyama H, Ohshima N, Imazeki T, Yamada T. Autologous blood donation with recombinant human erythropoietin in anemic patients. Ann Thorac Surg. 1999 Nov;68(5):1652-6. — View Citation

Koch CG, Li L, Van Wagoner DR, Duncan AI, Gillinov AM, Blackstone EH. Red cell transfusion is associated with an increased risk for postoperative atrial fibrillation. Ann Thorac Surg. 2006 Nov;82(5):1747-56. — View Citation

Kulier A, Levin J, Moser R, Rumpold-Seitlinger G, Tudor IC, Snyder-Ramos SA, Moehnle P, Mangano DT; Investigators of the Multicenter Study of Perioperative Ischemia Research Group; Ischemia Research and Education Foundation. Impact of preoperative anemia on outcome in patients undergoing coronary artery bypass graft surgery. Circulation. 2007 Jul 31;116(5):471-9. Epub 2007 Jul 9. — View Citation

Kyo S, Omoto R, Hirashima K, Eguchi S, Fujita T. Effect of human recombinant erythropoietin on reduction of homologous blood transfusion in open-heart surgery. A Japanese Multicenter study. Circulation. 1992 Nov;86(5 Suppl):II413-8. — View Citation

Murphy GJ, Reeves BC, Rogers CA, Rizvi SI, Culliford L, Angelini GD. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation. 2007 Nov 27;116(22):2544-52. Epub 2007 Nov 12. — View Citation

Paone G, Brewer R, Theurer PF, Bell GF, Cogan CM, Prager RL; Michigan Society of Thoracic and Cardiovascular Surgeons. Preoperative predicted risk does not fully explain the association between red blood cell transfusion and mortality in coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2012 Jan;143(1):178-85. doi: 10.1016/j.jtcvs.2011.09.015. Epub 2011 Oct 19. — View Citation

Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, Song HK, Clough ER; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion, Shore-Lesserson LJ, Goodnough LT, Mazer CD, Shander A, Stafford-Smith M, Waters J; International Consortium for Evidence Based Perfusion, Baker RA, Dickinson TA, FitzGerald DJ, Likosky DS, Shann KG. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011 Mar;91(3):944-82. doi: 10.1016/j.athoracsur.2010.11.078. Review. — View Citation

Sowade O, Warnke H, Scigalla P, Sowade B, Franke W, Messinger D, Gross J. Avoidance of allogeneic blood transfusions by treatment with epoetin beta (recombinant human erythropoietin) in patients undergoing open-heart surgery. Blood. 1997 Jan 15;89(2):411-8. — View Citation

Surgenor SD, DeFoe GR, Fillinger MP, Likosky DS, Groom RC, Clark C, Helm RE, Kramer RS, Leavitt BJ, Klemperer JD, Krumholz CF, Westbrook BM, Galatis DJ, Frumiento C, Ross CS, Olmstead EM, O'Connor GT. Intraoperative red blood cell transfusion during coronary artery bypass graft surgery increases the risk of postoperative low-output heart failure. Circulation. 2006 Jul 4;114(1 Suppl):I43-8. — View Citation

Van Mieghem NM, Nuis RJ, Tzikas A, Piazza N, Schultz C, Serruys PW, de Jaegere PP. Prevalence and prognostic implications of baseline anaemia in patients undergoing transcatheter aortic valve implantation. EuroIntervention. 2011 Jun;7(2):184-91. doi: 10.4244/EIJV7I2A32. — View Citation

van Straten AH, Hamad MA, van Zundert AJ, Martens EJ, Schönberger JP, de Wolf AM. Preoperative hemoglobin level as a predictor of survival after coronary artery bypass grafting: a comparison with the matched general population. Circulation. 2009 Jul 14;120(2):118-25. doi: 10.1161/CIRCULATIONAHA.109.854216. Epub 2009 Jun 29. — View Citation

Weltert L, D'Alessandro S, Nardella S, Girola F, Bellisario A, Maselli D, De Paulis R. Preoperative very short-term, high-dose erythropoietin administration diminishes blood transfusion rate in off-pump coronary artery bypass: a randomized blind controlled study. J Thorac Cardiovasc Surg. 2010 Mar;139(3):621-6; discussion 626-7. doi: 10.1016/j.jtcvs.2009.10.012. Epub 2009 Dec 29. — View Citation

Yazicioglu L, Eryilmaz S, Sirlak M, Inan MB, Aral A, Tasöz R, Eren NT, Kaya B, Akalin H. Recombinant human erythropoietin administration in cardiac surgery. J Thorac Cardiovasc Surg. 2001 Oct;122(4):741-5. — View Citation

Yoo YC, Shim JK, Kim JC, Jo YY, Lee JH, Kwak YL. Effect of single recombinant human erythropoietin injection on transfusion requirements in preoperatively anemic patients undergoing valvular heart surgery. Anesthesiology. 2011 Nov;115(5):929-37. doi: 10.1097/ALN.0b013e318232004b. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

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