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

Study Overview
=================
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.

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

Conditions
-----------------
Acute Kidney Injuries, Kidney Injuries, Acute, Kidney Injury, Acute, Acute Renal Injury, Acute Renal Injuries

Intervention / Treatment
-----------------
* Drug: Spironolactone


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spironolactone<br>The intervention group will receive spironolactone. The drug will be 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. | Drug: Spironolactone<br>* 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.<br>* Other names: Vivitar;|
| No Intervention: No spironolactone<br>Cardiac surgical patients requiring cardiopulmonary bypass and aortic cross clamp, randomised not to receive spironolactone will be followed for 10 days after surgery. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute kidney injury (AKI) defined by the AKIN criteria in patients submitted to cardiac surgery with spironolactone therapy. |  | First 10 days after cardiac surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Mortality | Mortality in patients submitted to cardiac surgery with or without previous spironolactone therapy. | First 10 days after cardiac surgery | 
| Hyperkalemia | Hyperkalemia in patients submitted to cardiac surgery with or without previous spironolactone therapy. | First 10 days after cardiac surgery | 
| Renal replacement therapy | Renal replacement therapy in patients submitted to cardiac surgery with or without previous spironolactone therapy. | First 10 days after cardiac surgery | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute kidney injury, Spironolactone