Erythropoietin + Iron Therapy for Anemic Patients Undergoing Aortic Valve Replacement

NCT02390102 | Completed Phase 3

• 2 other identifiers: EPICURECER-20809
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

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.

Conditions

Anemia; Aortic Stenosis

Keywords

Anemia; Severe aortic stenosis; Red blood cell transfusion; Erythropoietin

Outcome Measures

Primary Outcomes (1)

• Rate of red blood cell transfusion

  30 days

Secondary Outcomes (13)

• Number of packets of red cells

  30 days

• Hemoglobin value

  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

  At 48 hours following procedure

Study Arms (2)

Erythropoietin

ACTIVE COMPARATOR

Dose: darboepoetin 0.75µg/Kg + 200mg intravenous iron sucrose Administered at days 10 (±4) and 1 (±1) before the index procedure.

Drug: Erythropoietin

Placebo

PLACEBO COMPARATOR

Dosage: Saline solution 0.9% Administered at days 10 (±4) and 1 (±1) before the index procedure.

Drug: Placebo

Interventions

Erythropoietin DRUG

Combinaison drug of darboepoetin 0.75µg/Kg + 200mg intravenous iron sucrose

Also known as: Darboepoetin

Erythropoietin

Placebo DRUG

Saline solution 0.9%

Also known as: Saline solution

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec: lead

Study Sites (1)

Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Québec, G1V 4G5, Canada

Location

Related Publications (20)

• 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.

  PMID: 18172032 BACKGROUND

• 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. doi: 10.1161/CIRCULATIONAHA.106.653501. Epub 2007 Jul 9.

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• 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. doi: 10.1016/j.athoracsur.2005.03.137.

  PMID: 16181875 BACKGROUND

• 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.

  PMID: 21646060 BACKGROUND

• van Straten AH, Hamad MA, van Zundert AJ, Martens EJ, Schonberger 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.

  PMID: 19564556 BACKGROUND

• 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.

  PMID: 21353044 BACKGROUND

• 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. doi: 10.1161/CIRCULATIONAHA.107.698977. Epub 2007 Nov 12.

  PMID: 17998460 BACKGROUND

• 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. doi: 10.1016/s0003-4975(02)04370-9.

  PMID: 12607656 BACKGROUND

• 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.

  PMID: 22014719 BACKGROUND

• 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. doi: 10.1016/j.athoracsur.2006.05.045.

  PMID: 17062241 BACKGROUND

• 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. doi: 10.1161/CIRCULATIONAHA.105.001271.

  PMID: 16820613 BACKGROUND

• Bagur R, Webb JG, Nietlispach F, Dumont E, De Larochelliere R, Doyle D, Masson JB, Gutierrez MJ, Clavel MA, Bertrand OF, Pibarot P, Rodes-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.

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• 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.

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• 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. doi: 10.1016/s0003-4975(99)00755-9.

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• 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.

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• 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.

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  PMID: 1424032 BACKGROUND

• Nishiwaki H, Abe Y, Suzuki T, Hasegawa T, Levack WM, Noma H, Ota E. Erythropoiesis-stimulating agents for preventing acute kidney injury. Cochrane Database Syst Rev. 2024 Sep 20;9(9):CD014820. doi: 10.1002/14651858.CD014820.pub2.

  PMID: 39301879 DERIVED

MeSH Terms

Conditions

Anemia; Aortic Valve Stenosis

Interventions

Erythropoietin; Saline Solution

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Josep Rodes Cabau, MD

  Institut Universitaire de Cardiologie et de Pneumologie de Quebec

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 21, 2013
• First Posted: March 17, 2015
• Study Start: June 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2016
• Last Updated: July 17, 2018

Record last verified: 2018-07

Locations

CA (1)