Oral and Intravenous Iron in Patients Postoperative Cardiovascular Surgery Under Extracorporeal Circulation

Anaemia Clinical Trial

Official title:

A Phase IV, Unicenter, Randomized, Double-Blind, Parallel-Group, Comparaty Study of Intravenous and Oral Iron vs Placebo in Patient Under Extracorporeal Circulation in Cardiovascular Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01078818
• Other study ID #: Tratamiento con hierro/2007
• Status: Completed
• Phase: Phase 4
• First received: March 1, 2010
• Last updated: March 2, 2010
• Start date: May 2007
• Est. completion date: May 2009

Study information

• Verified date: May 2007
• Source: Fundación Canaria Rafael Clavijo para la Investigación Biomédica
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

Anaemia is a common postoperative problem of cardiovascular surgery after cardiopulmonary bypass (CPB). Because of this the need for hemoderived blood transfusions is high. The purpose of this study was to compare the clinical efficacy of intravenous and oral iron in anaemia and the impact of the iron on the transfusion rate in postoperative cardiovascular surgery under extracorporeal circulation.

Description:

Prospective double dummy triple blind study of 159 patients undergoing CPB; randomised in 3 groups treated with iron intravenously (iv) (group I), with iron orally (group II) controlled with placebo (group III). Patients from group I were treated with iv Iron sucrose , three doses of 100 mg of iv iron every 24 hours during postoperative hospitalization and 1 pill/24 h of oral placebo during the first month after discharge. Group II was programmed to receive 1 iron pill orally every 24 hours pre and postoperatively and up to one month after discharge and a placebo while hospitalized. Group III was programmed to receive an oral and iv placebo pre and postoperatively.

Variables were collected preoperatively, at operation room and at Intensive Care Unit admission and discharge, at postoperative floor discharge and at one month after surgical discharge.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 78 Years

Eligibility

Inclusion Criteria:

• Men and women = 18 years of age

• Patients subject to elective cardiac surgery under extracorporeal circulation

• Patients without previous anaemia, susceptible of treatment

• Patients without need of blood transfusion preoperative

• Patients providing written informed consent

• Patients who are able to complete all study visits per protocol

Exclusion Criteria:

• Patients subject to elective cardiac surgery, but without extracorporeal circulation

• Patients who were treated with fibrinolytic therapy 48 hours before the surgery

• Patients with history of impaired renal function, (e.g., calculated creatinine clearance <50 mL/min/1.73 m2)

• Patients operated of active endocarditis

• Redo-surgery patients

• Women who are pregnant or lactating

• Patients with clinical of digestive bleeding

• Patients with vitamin B12 deficit

• Patients with ferropenic anaemia

• Patients with clinical history of asthma or allergy

• Patients with active infection

• Patients who are included in another clinical study

• Patients with hepatic disease

• Patients with history of allergy to iron

• Patients unlikely to adhere to protocol follow-up

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anaemia

Intervention

Drug:
• IV trivalent saccharose hydroxide ferrous
Preoperative Period 5-10 days 200 mg Iron iv (Venofer® )in 200cc physiologic solution /24-48h x 3 dosis +1 oral placebo /24h Postoperative Period 1-3weeks 200 mg Iron iv (Venofer® )in 200cc physiologic solution/24-48h x 3 dosis + 1 oral placebo /24h One month Follow-up 1 month 1 oral placebo /24h
• Oral ferrous fumarate
200cc physiologic solution iv placebo /24-48h x 3 dosis + 1 oral iron tablet/24h (Ferogradumet®) Postoperative Period: 200cc physiologic solution iv placebo /24-48h x 3 dosis + 1 oral iron tablet/24h (Ferogradumet®) One month Follow-up: 1 oral iron tablet/24h Ferogradumet
• Oral and intravenous Placebo
Preoperative Period:1oral placebo/24h Postoperative Period:200cc physiologic solution iv placebo /24-48h x 3 dosis + 1oral placebo/24h One month Follow-up:1 oral placebo/24h

Locations

Country	Name	City	State
Spain	Hospital Universitario de Canarias	Tenerife	Santa Cruz de Tenerife

Sponsors (1)

Lead Sponsor	Collaborator
Fundación Canaria Rafael Clavijo para la Investigación Biomédica

Country where clinical trial is conducted

Spain, 

References & Publications (14)

Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999 Dec 23;341(26):1986-95. Review. Erratum in: N Engl J Med 2000 Feb 3;342(5):364. — View Citation

Boyle EM Jr, Lille ST, Allaire E, Clowes AW, Verrier ED. Endothelial cell injury in cardiovascular surgery: atherosclerosis. Ann Thorac Surg. 1997 Mar;63(3):885-94. Review. — View Citation

Bracey AW, Radovancevic R, Riggs SA, Houston S, Cozart H, Vaughn WK, Radovancevic B, McAllister HA Jr, Cooley DA. Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome. Transfusion. 1999 Oct;39(10):1070-7. — View Citation

Butler J, Rocker GM, Westaby S. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg. 1993 Feb;55(2):552-9. Review. — View Citation

Chenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med. 1981 Feb 26;304(9):497-503. — View Citation

Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. N Engl J Med. 1987 Jul 23;317(4):249-51. — View Citation

Fishbane S, Kowalski EA. The comparative safety of intravenous iron dextran, iron saccharate, and sodium ferric gluconate. Semin Dial. 2000 Nov-Dec;13(6):381-4. Review. — View Citation

Fuhrer G, Gallimore MJ, Heller W, Hoffmeister HE. Aprotinin in cardiopulmonary bypass--effects on the Hageman factor (FXII)--Kallikrein system and blood loss. Blood Coagul Fibrinolysis. 1992 Feb;3(1):99-104. — View Citation

Goodnough LT, Skikne B, Brugnara C. Erythropoietin, iron, and erythropoiesis. Blood. 2000 Aug 1;96(3):823-33. Review. — View Citation

Huyzen RJ, van Oeveren W, Wei F, Stellingwerf P, Boonstra PW, Gu YJ. In vitro effect of hemodilution on activated clotting time and high-dose thrombin time during cardiopulmonary bypass. Ann Thorac Surg. 1996 Aug;62(2):533-7. — View Citation

Kirklin JW. Open-heart surgery at the Mayo Clinic. The 25th anniversary. Mayo Clin Proc. 1980 May;55(5):339-41. — View Citation

Madi-Jebara SN, Sleilaty GS, Achouh PE, Yazigi AG, Haddad FA, Hayek GM, Antakly MC, Jebara VA. Postoperative intravenous iron used alone or in combination with low-dose erythropoietin is not effective for correction of anemia after cardiac surgery. J Cardiothorac Vasc Anesth. 2004 Feb;18(1):59-63. — View Citation

Reuler JB. Hypothermia: pathophysiology, clinical settings, and management. Ann Intern Med. 1978 Oct;89(4):519-27. Review. — View Citation

Rohling RG, Zimmermann AP, Breymann C. Intravenous versus oral iron supplementation for preoperative stimulation of hemoglobin synthesis using recombinant human erythropoietin. J Hematother Stem Cell Res. 2000 Aug;9(4):497-500. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Haemoglobin and Hematocrit values	The objective was to compare the clinical efficacy of intravenous and oral iron in anaemia and the impact on the transfusion rate needing in Cardiovascular surgery under cardiopulmonary bypass	2 years	Yes
Secondary	need for hemoderived blood transfusions, postoperative stay and hospital costs	The objective was to compare the clinical efficacy of intravenous and oral iron in anaemia and the impact on the transfusion rate needing in Cardiovascular surgery under cardiopulmonary bypass	2 years	No