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The PERFECT RCT – How Urgent Should Appendectomy Be?

October 30, 2023

Written by Seth Walsh-Blackmore

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A multicenter, open RCT of adults with presumed uncomplicated appendicitis found no significant difference in perforation rates or complications with appendectomy before 8 or 24 hours.

Slow down…this appy needs to be PERFECT
The risk of progression and perforation is why many surgeons pursue appendectomy ASAP in uncomplicated appendicitis. This RCT adds high-level evidence to existing retrospective data which suggests under 24 hours is safe for uncomplicated adults, allowing more time for preoperative optimization.

This open-design non-inferiority trial included adult patients with acute appendicitis diagnosed via imaging or Adult Appendicitis Score ≥ 16 (high probability cutoff), then randomized to surgery within 8 or 24 hours. Patients with pregnancy or concern for perforation were excluded. Patients were randomized again within their groups to receive preoperative antibiotics for an upcoming RCT.

There were 1,822 patients randomized, with 1,803 ultimately undergoing surgery and included in the Intention-to-treat analysis with 30-day follow-up. This met the 90% power estimate of 1,800 patients to detect a 5% difference in perforation intraoperatively (AAST grade 3-5) as the non-inferiority margin.

An absolute difference in perforation of 0.6% (95%CI -2.1 to 3.2%) occurred, meaning 24 hours was noninferior to 8. There was no significant difference in postoperative complications over 30 days.

Only 63% of the <8 hour and 88% of the <24 hour group received surgery within the designated window. However, a per-protocol analysis was consistent with the ITT analysis. A post hoc subgroup analysis found an absolute difference of 3.1% (95% CI -0.2% to 6.4%) in perforation at 8-24h vs. 8h. This subset analysis does not control for confounders (i.e. antibiotics) like the primary analysis and does not establish inferiority. This substantial multicenter sample had balanced reported AAST grades across all groups despite the risk of observation bias with its open design.

How will this change my practice?
The data do not change the need to diagnose appendicitis ASAP as an EP but may affect the decision-making of the surgical team. I am interested in this upcoming antibiotic RCT.

Editor’s note: The authors’ selection of a 5% difference in perforation seems like a high noninferiority margin to me. Though the study’s upper CI was <5% (noninferior), up to a 3.2% higher perforation rate – a really bad outcome – by waiting 24 hours is concerning. It seems like best practice is to operate ASAP. ~Clay Smith

Role of preoperative in-hospital delay on appendiceal perforation while awaiting appendicectomy (PERFECT): a Nordic, pragmatic, open-label, multicentre, non-inferiority, randomized controlled trial.[published online ahead of print, 2023 Sep 14]. Lancet. 2023;S0140-6736(23)01311-9. doi:10.1016/S0140-6736(23)01311-9

What are your thoughts?