Randomized Clinical Trial Comparing On-clamp Versus Off-clamp Laparoscopic Partial Nephrectomy for Small Renal Masses (CLOCK II Laparoscopic Study): A Intention-to-treat Analysis of Perioperative Outcomes

Background: Recent randomized trials (RCTs) in the field of robotic partial nephrectomy (PN) showed no significant differences in perioperative outcomes between the off- and on-clamp approaches. Objective: To compare the perioperative outcomes of on- versus off-clamp pure laparoscopic PN (LPN). Design, setting, and participants: A multi-institutional analysis of the on- versus off-clamp approach during LPN in the setting of an RCT (CLOCK II trial; ClinicalTrials.gov NCT02287987) was performed. Intervention: Off- versus on-clamp LPN. Outcome measurements and statistical analysis: Baseline patient and tumor variables, and peri- and postoperative data were collected. Randomized allocation with a 1:1 ratio was assigned. Surgical strategy for managing the renal pedicle was dictated by the study protocol. In the off-clamp arm, the renal artery had to remain unclamped for the duration of the whole procedure. Reporting the intention-to-treat analysis is the purpose of the study. Results and limitations: The study recruited 249 patients. Of them, 123 and 126 were randomized and allocated into the on- and off-clamp treatment groups, respectively. Treatment groups were comparable at baseline after randomization with respect to patients’ demographics, comorbidities, renal function, and tumor size and complexity. A univariable analysis found no differences in the perioperative outcomes between the groups, including median (interquartile range) estimated blood loss (150 [100–200] vs 150 [100–250] ml, p = 0.2), grade ≥2 complication rate as classified according to the Clavien-Dindo system (5.7% vs 4.8%, p = 0.6), and positive surgical margin rate (8.2% vs 3.5% for the on- vs off-clamp group, p = 0.1). No differences were found in terms of the 1st (81.3 [66.7–94.3] vs 85.3 [71.0–97.7] ml/min, p = 0.2) and 5th postoperative days estimated glomerular filtration rate (83.3 [70.5–93.7] vs 83.4 [68.6–139.3] ml/min, p = 0.2). A multivariable analysis found each +1 increase in RENAL score corresponded to an increase in the protection from the occurrence of complications (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.54–0.97, p = 0.034), while each +1 cm increase in tumor size corresponded to an increase in the risk of blood transfusion (OR 1.39, 95% CI 1.14–1.70, p = 0.001). Conclusions: In the setting of an RCT, no differences were found in the perioperative and early functional outcomes between on- and off-clamp LPN. Patient summary: In this study, we investigated, by means of a randomized trial, whether avoiding the clamping of renal artery during laparoscopic resection of renal mass is able to translate into benefits. We found no differences in terms of safety, efficacy, and renal function from the standard approach, which includes arterial clamping.