Short Term Spironolactone for Prevention of Acute Kidney Injury After Cardiac Surgery

Acute Renal Injury Clinical Trial

Official title:

Pilot Non Randomised Controlled Trial of Short Term Spironolactone Use for Prevention of Acute Kidney Injury After Cardiac Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02417896
• Other study ID #: SPIRO-110313
• Status: Recruiting
• Phase: N/A
• First received: April 13, 2015
• Last updated: April 15, 2015
• Start date: April 2013
• Est. completion date: July 2015

Study information

• Verified date: March 2013
• Source: Instituto Nacional de Cardiologia Ignacio Chavez
• Contact: Magdalena Madero, M.D.
• Phone: 55736902
• Email: madero.magdalena[@]gmail.com
• Is FDA regulated: No
• Health authority: Mexico: National Council of Science and Technology
• Study type: Interventional

Clinical Trial Summary

Our aim is to test whether short term perioperative administration of oral spironolactone could reduce incidence of postoperative acute kidney injury (AKI) in cardiac surgical patients.

Description:

Adult patients (>18 years old) were eligible for the study if they were undergoing elective or emergency cardiac surgery requiring CPB and aortic cross clamp. Exclusion criteria were patients with preoperative chronic renal insufficiency (Serum creatinine >1.6 mg/dl) or on dialysis, hyperkalemia (>5.0 mEq/L), AKI detected up to 24 hours before the procedure; patients receiving contrast agents 72 hours before surgery, planned off-pump cardiac surgery, hypersensitivity, allergy or known intolerance to spironolactone and pregnancy. Patients that died during the surgical procedure or 24 hours after surgery were eliminated from the analysis, as well as patients that did not receive spironolactone during the postoperative period. Criteria for stopping spironolactone were serum potassium >5.5 mEq/L, a serum creatinine level ≥2.5 mg/dL and urine output of <0.3 ml/k/hr during 8 hours.

One day prior to the procedure, patients that met the inclusion criteria were invited to participate in the trial, signing an informed consent. Spironolactone was administered orally by a study investigator (100 mg 12-24 hrs before surgery); subsequently three further doses of 25 mg were administered orally in postoperative days 1, 2 and 3. Thus, a total 1 x 100 mg and 3 x 25 mg doses of spironolactone in the intervention group were be given. If the patient had not been extubated, spironolactone was administered nasogastrically. Oral drugs were delayed by up to 4 hours if extubation had just occurred. The patients that decided not to receive spironolactone were followed during the study period and considered as controls. Preexisting ACE inhibitor, angiotensin receptor blocker, or MR antagonist were not suspended before surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Informed consent

• Elective and emergent cardiac surgery with cardiopulmonary bypass and aortic cross clamp

Exclusion Criteria:

• Patients with preoperative chronic renal insufficiency on dialysis

• Acute kidney injury detected up to 24 hours before the procedure a

• Patients receiving contrast agents 72 hours before surgery

• Planned off-pump cardiac surgery

• Hypersensitivity, allergy or known intolerance to spironolactone

• Pregnancy

• Hyperkalemia with potassium >5.0 mEq/L

Criteria for stopping study medication:

• Serum potassium >5.5 mEq/L

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Kidney Injuries
• Acute Kidney Injury
• Acute Renal Injuries
• Acute Renal Injury
• Kidney Injuries, Acute
• Kidney Injury, Acute

Intervention

Drug:
• Spironolactone
Spironolactone is administered orally to cardiac surgical patients by a study investigator (100 mg 12-24 hrs before surgery); subsequently three further doses of 25 mg are administered orally in the morning of postoperative days 1, 2 and 3. A total 1 x 100 mg and 3 x 25 mg doses of spironolactone in the intervention group will be given. If the patient has not been extubated, spironolactone is administered nasogastrically. Oral drugs will be delayed by up to 4 hours if extubation has just occurred.

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Cardiología Ignacio Chávez	Mexico City	Distrito Federal
Mexico	Instituto Nacional de la Nutrición Salvador Zubirán	Mexico City	Distrito Federal

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Nacional de Cardiologia Ignacio Chavez	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Country where clinical trial is conducted

Mexico, 

References & Publications (5)

Barrera-Chimal J, Pérez-Villalva R, Cortés-González C, Ojeda-Cervantes M, Gamba G, Morales-Buenrostro LE, Bobadilla NA. Hsp72 is an early and sensitive biomarker to detect acute kidney injury. EMBO Mol Med. 2011 Jan;3(1):5-20. doi: 10.1002/emmm.201000105. Epub 2010 Dec 14. — View Citation

Barrera-Chimal J, Pérez-Villalva R, Rodríguez-Romo R, Reyna J, Uribe N, Gamba G, Bobadilla NA. Spironolactone prevents chronic kidney disease caused by ischemic acute kidney injury. Kidney Int. 2013 Jan;83(1):93-103. doi: 10.1038/ki.2012.352. Epub 2012 Sep 26. — View Citation

Pretorius M, Murray KT, Yu C, Byrne JG, Billings FT 4th, Petracek MR, Greelish JP, Hoff SJ, Ball SK, Mishra V, Body SC, Brown NJ. Angiotensin-converting enzyme inhibition or mineralocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery. Crit Care Med. 2012 Oct;40(10):2805-12. — View Citation

Prowle JR, Calzavacca P, Licari E, Ligabo EV, Echeverri JE, Haase M, Haase-Fielitz A, Bagshaw SM, Devarajan P, Bellomo R. Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery. Nephrology (Carlton). 2012 Mar;17(3):215-24. doi: 10.1111/j.1440-1797.2011.01546.x. — View Citation

Sánchez-Pozos K, Barrera-Chimal J, Garzón-Muvdi J, Pérez-Villalva R, Rodríguez-Romo R, Cruz C, Gamba G, Bobadilla NA. Recovery from ischemic acute kidney injury by spironolactone administration. Nephrol Dial Transplant. 2012 Aug;27(8):3160-9. doi: 10.1093/ndt/gfs014. Epub 2012 Apr 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute kidney injury (AKI) defined by the AKIN criteria in patients submitted to cardiac surgery with spironolactone therapy.		First 10 days after cardiac surgery	Yes
Secondary	Change in urinary neutrophil gelatinase-associated lipocalin (NGAL) concentration.	Change in urinary neutrophil gelatinase-associated lipocalin (NGAL) concentration in patients submitted to cardiac surgery with or without previous spironolactone therapy.	First 10 days after cardiac surgery	Yes
Secondary	Mortality	Mortality in patients submitted to cardiac surgery with or without previous spironolactone therapy.	First 10 days after cardiac surgery	Yes
Secondary	Hyperkalemia	Hyperkalemia in patients submitted to cardiac surgery with or without previous spironolactone therapy.	First 10 days after cardiac surgery	Yes
Secondary	Renal replacement therapy	Renal replacement therapy in patients submitted to cardiac surgery with or without previous spironolactone therapy.	First 10 days after cardiac surgery	Yes
Secondary	Length of stay in intensive care unit	Length of stay in intensive care unit or patients submitted to cardiac surgery with or without previous spironolactone therapy.	First 20 days after cardiac surgery	Yes