Perioperative morbidity of clamp vs off‐clamp robotic partial nephrectomy: preliminary results from a multicentre randomized clinical trial (the clock study): mp49‐02

INTRODUCTION AND OBJECTIVES: To assess the significance of mannitol used as renal protective agent during nephronsparing surgery (NSS) on renal functional outcomes after NSS. METHODS: A prospective, randomized, placebo-controlled, double-blind, phase 3 trial (ClinicalTrials.gov identifier NCT01606787) designed to detect a 5% difference between treatment arms with a power of 90%. Patients were randomized 1:1 to receive mannitol (12.5 g) or normal saline solution placebo intravenously within 30 min prior to renal vascular clamping. Eligibility criteria included age >18 yr, renal artery clamping during NSS, and preoperative estimated glomerular filtration rate (eGFR) >45 mL/min/1.73m. Intraoperatively, a standardized fluid management algorithm was used to maintain hemodynamic stability and urine output 0.5 mL/kg/h. Postoperatively, eGFR was obtained at 6 wk and 6 mo. A renal scan was obtained pre operatively and at the 6-mo endpoint. An ANCOVA model was used to assess the differences in eGFR at 6 wk and 6 mo, and in renal scan at 6 mo after NSS. Differences in grade 3-5 complications were assessed using Fisher0s exact test. At the interim analysis on the first 88 patients, the O0Brien-Fleming stopping boundaries requiring a significance level of 0.0031 were not met (p 1⁄4 0.6). RESULTS: A total of 105 patients per treatment arm were enrolled. After excluding 11 patients (7 in the placebo and 4 in the mannitol arm) who did not undergo NSS; 2 patients (1 in each arm) converted to radical nephrectomy, and 1 patient from the mannitol arm who never received the study drug, 98 and 101 patients in the placebo and mannitol arms, respectively, were evaluated. Median age was 56 yr (interquartile range [IQR] 48, 63) and 60 yr (IQR 50, 66) in the placebo and mannitol arm, respectively. Comparing placebo to the mannitol arm, the adjusted difference of 0.2 eGFR units at 6 mo after NSS was not significant (95% confidence interval [CI] -3.1, 3.5; p1⁄4 0.9). The adjusted difference of -2.6 eGFR units at 6 wk after NSS was not significant (95% CI -5.8, 0.7; p 1⁄4 0.12). No significant differences were detected between treatment arms in median split function on 6-mo renal scan (difference -1.7; 95% CI -3.8, 0.4; p 1⁄4 0.11), or in grade 3-5 complication rates within 90 days of NSS (difference 3.2%; 95% CI -4.1%, 11%; p 1⁄4 0.4). CONCLUSIONS: This randomized prospective trial provides evidence against the use of mannitol as renal protective agent during NSS since no clinical or statistically significant advantage to the use of intravenous mannitol in patients undergoing NSS was found.