Intravenous sildenafil citrate and post-cardiac surgery acute kidney injury: a double-blind, randomised, placebo-controlled trial

Abstract

Background: This study assessed whether i.v. sildenafil citrate prevented acute kidney injury in at-risk patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: In a double-blind RCT, adults at increased risk of acute kidney injury undergoing cardiac surgery in a single UK tertiary centre were randomised to receive sildenafil citrate 12.5 mg kg À1 i.v. over 150 min or dextrose 5% at the commencement of surgery. The primary outcome was serum creatinine measured at six post-randomisation time points. The primary analysis used a linear mixed-effects model adjusted for the stratification variables, baseline estimated glomerular filtration rate, and surgical procedure. Secondary outcomes considered clinical events and potential disease mechanisms. Effect estimates were expressed as mean differences (MDs) or odds ratios with 95% confidence intervals. Results: The analysis population comprised eligible randomised patients that underwent valve surgery or combined coronary artery bypass graft and valve surgery, with cardiopulmonary bypass, between May 2015 and June 2018. There were 60 subjects in the sildenafil group and 69 in the placebo control group. The difference between groups in creatinine concentration was not statistically significant (MD: 0.88 mmol L À1 [e5.82, 7.59]). There was a statistically significant increase in multiple organ dysfunction scores in the sildenafil group (MD: 0.54 [0.02, 1.07]; P¼0.044). Secondary outcomes, and biomarkers of kidney injury, endothelial function, and inflammatory cell activation, were not significantly different between the groups. Conclusions: These results do not support the use of i.v. sildenafil citrate for kidney protection in adult cardiac surgery. Clinical trial registration: ISRCTN18386427.

Activation of the innate immune response and organ injury after cardiac surgery: a systematic review and meta-analysis of randomised trials and analysis of individual patient data from randomised and non-randomised studies

“…21 REVAKI-2: the effect of sildenafil (REVatio®), a phosphodiesterase type 5 inhibitor, on postcardiac surgery acute kidney injury: a randomised, placebo-controlled Phase IIb clinical trial. 22 REDWASH: a randomised controlled trial of red cell washing for the attenuation of transfusion-associated organ injury in cardiac surgery. 23 MaRACAS: an observational caseecontrol study to identify the role of microvesicles and microvesicle-derived micro-RNA in post-cardiac surgery acute kidney injury (MaRACAS).…”

Urinary extracellular vesicles and micro-RNA as markers of acute kidney injury after cardiac surgery

“…Between September 2015 and September 2018, 1,062 patients undergoing cardiovascular surgery were screened for participation in the REVAKI-2 trial 11 . Three hundred nine were eligible, out of which 180 declined consent, resulting in 125 included patients.…”

“…Predictive accuracy biomarker study performed in the cohort of the REVAKI-2 trial (registration ISRCTN18386427) that tested the effect of sildenafil (REVATIO®) on post-cardiac surgery acute kidney injury. The trial was a single centre parallel-group randomized clinical trial that has been published previously 11 . All participants in REVAKI-2 provided written informed consent to participate in the trial before their operation.…”

Urinary extracellular vesicles and micro-RNA as markers of acute kidney injury after cardiac surgery

“…Between September 2015 and September 2018, 1062 patients undergoing cardiovascular surgery were screened for participation in the REVAKI-2 trial [11]. Three hundred nine were eligible, out of which 180 declined consent, resulting in 125 included patients.…”

“…The trial was a single center parallel-group randomized clinical trial that has been published previously. [11] All participants in REVAKI-2 provided written informed consent to participate in the trial before their operation. The trial complied with the Declaration of Helsinki.…”