Clinical trial NCT02417896: Short Term Spironolactone for Prevention of Acute Kidney Injury After Cardiac Surgery
Official title: Pilot Non Randomised Controlled Trial of Short Term Spironolactone Use for Prevention of Acute Kidney Injury After Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute Kidney Injuries
Kidney Injuries, Acute
Kidney Injury, Acute
Acute Renal Injury
Acute Renal Injuries
Keywords: Acute kidney injury
Spironolactone
Lead sponsor: Instituto Nacional de Cardiologia Ignacio Chavez
Sponsor class: OTHER
Collaborators: name: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
First posted: 2015-04-16
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Acute kidney injury (AKI) defined by the AKIN criteria in patients submitted to cardiac surgery with spironolactone therapy.
timeFrame: First 10 days after cardiac surgery
Secondary outcomes:
measure: Change in urinary neutrophil gelatinase-associated lipocalin (NGAL) concentration.
timeFrame: First 10 days after cardiac surgery
measure: Mortality
timeFrame: First 10 days after cardiac surgery
measure: Hyperkalemia
timeFrame: First 10 days after cardiac surgery
measure: Renal replacement therapy
timeFrame: First 10 days after cardiac surgery
measure: Length of stay in intensive care unit
timeFrame: First 20 days after cardiac surgery
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de la Nutrición Salvador Zubirán
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cardiología Ignacio Chávez
state: Distrito Federal
Study officials:
affiliation: Instituto Nacional de la Nutrición Salvador Zubiran
name: Gerardo Gamba, PhD
role: STUDY_DIRECTOR
References:
citation: Barrera-Chimal J, Perez-Villalva R, Rodriguez-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.
citation: Sanchez-Pozos K, Barrera-Chimal J, Garzon-Muvdi J, Perez-Villalva R, Rodriguez-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.
citation: Barrera-Chimal J, Perez-Villalva R, Cortes-Gonzalez 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.
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.
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. doi: 10.1097/CCM.0b013e31825b8be2.