Role of Delay and Antibiotics on Perforation Rate While Waiting Appendectomy (PERFECT)

Role of Delay and Antibiotics on PERForation Rate While Waiting appendECTomy - Randomized Non-inferiority Trial

This study evaluates the effects of preoperative delay and antibiotics on perforation rate of appendix while waiting surgery for acute appendicitis. Patients with diagnosed acute appendicitis are randomized into two urgency groups: surgery within 8 hours or surgery within 24 hours. In addition, patients are randomized to either receive antibiotics while waiting or waiting without antibiotics.

Study Overview

• Status: Completed
• Conditions: Appendicitis
• Intervention / Treatment: Drug: No antibiotics; Other: urgent schedule; Other: less urgent schedule; Drug: Antibiotics, cefuroxime and metronidazole

• Study Type: Interventional
• Enrollment (Actual): 1800
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Espoo, Finland
    • HUS, Jorvi Hospital
  • Helsinki, Finland, 00029
    • HUS, Meilahti Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acute appendicitis where surgery is planned. Diagnosis of appendicitis should be verified either by clinical diagnosis with Adult Appendicitis Score >=16 or by diagnostic imaging (CT-scan, MRI or ultrasound) showing appendicitis. All patients with symptoms at least 3 days should undergo diagnostic imaging before inclusion.

Exclusion Criteria:

• Complicated appendicitis according to diagnostic imaging. The following findings indicate complicated appendicitis: extraluminal air or extraluminal fecalith; fluid collection, abscess or phlegmon next to appendix; non-enhancement appendiceal wall on contrast enhanced CT-scan.
• Plasma C-reactive protein >=100
• Fever measured on emergency department over 38.5 degrees Celcius.
• Clinical generalized peritonitis or other reason that indicate immediate surgery
• Pregnancy, pregnancy test is taken from all fertile aged women before randomization
• Allergy to study antibiotics, or anaphylactic reaction after betalactam antibiotic or other contraindication for metronidazole or ongoing antibiotic treatment or patient is carrier of resistant bacteria. (This exclusion criteria are applicable only on randomization into antibiotic treatment arms)
• Missing written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Surgery within 8 hours, no antibiotics; Patients are planned for urgent operation, that should be done within 8 hours. Operation can be done during the night time. Patients do not receive antibiotics while waiting surgery. Prophylactic antibiotics are given 0-30 minutes before incision.	Drug: No antibiotics; No antibiotics are given while waiting surgery.; Other: urgent schedule; Patients can wait up to 8 hours for surgery.
Experimental: Surgery within 24 hours, no antibiotics; Patients are planned for urgent operation, that should be done within 24 hours. Operations are not done during the night time (00:00 - 08:00), unless necessary to avoid delay over 24 hours. Patients do not receive antibiotics while waiting surgery. Prophylactic antibiotics are given 0-30 minutes before incision.	Drug: No antibiotics; No antibiotics are given while waiting surgery.; Other: less urgent schedule; Patients can wait up to 24 hours for surgery.
Experimental: Surgery within 8 hours, antibiotics; Patients are planned for urgent operation, that should be done within 8 hours. Antibiotics (cefuroxime 1.5g and metronidazole 500mg every 8 hours) are given while waiting surgery.	Other: urgent schedule; Patients can wait up to 8 hours for surgery.; Drug: Antibiotics, cefuroxime and metronidazole; Patient receives antibiotics while waiting appendectomy
Experimental: Surgery within 24 hours, antibiotics; Patients are planned for urgent operation, that should be done within 24 hours. Operations are not done during the night time (00:00 - 08:00), unless necessary to avoid delay over 24 hours. Antibiotics (cefuroxime 1.5g and metronidazole 500mg every 8 hours) are given while waiting surgery.	Other: less urgent schedule; Patients can wait up to 24 hours for surgery.; Drug: Antibiotics, cefuroxime and metronidazole; Patient receives antibiotics while waiting appendectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complicated appendicitis	Surgical finding is complicated appendicitis (AAST Grade III-V)	during surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of hospital stay	Time in hours from randomization to discharge from hospital	30 days from surgery
Postoperative complications	complications are defined according to Clavien-Dindo classification	30 days from surgery
Pain measured by numeric rating scale while waiting surgery	Pain is measured by numeric rating scale (NRS) every hour by patient, and area under NRS represents overall pain.	up to 36 hours
Surgical site infections (SSI) and positive blood cultures	SSIs classified according to CDC classification: superficial incisional, deep incisional and organ/space infection. Blood cultures are obtained if patient has fever over 38.5 degrees Celcius.	within 30 days from randomization
Conversions of laparoscopic surgeries to open surgery	All surgeries are started as laparoscopic surgery. Conversion means that operation is converted to open surgery during the same operation.	during the the first operation for acute appendicitis
Gangrenous or perforated appendicitis according to pathological examination.	All specimens are sent to pathological examination and all pathological reports are reviewed	3 week after surgery
Sunshine Appendicitis Grading System Score classification	Sunshine Appendicitis Grading System Score (range 0-4) for appendicitis. Higher score represents worse outcome	during surgery

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Investigators: Principal Investigator: Panu J Mentula, MD, Helsinki University Central Hospital

Publications and helpful links

General Publications

• Sammalkorpi HE, Mentula P, Leppaniemi A. A new adult appendicitis score improves diagnostic accuracy of acute appendicitis--a prospective study. BMC Gastroenterol. 2014 Jun 26;14:114. doi: 10.1186/1471-230X-14-114.
• Shafi S, Aboutanos M, Brown CV, Ciesla D, Cohen MJ, Crandall ML, Inaba K, Miller PR, Mowery NT; American Association for the Surgery of Trauma Committee on Patient Assessment and Outcomes. Measuring anatomic severity of disease in emergency general surgery. J Trauma Acute Care Surg. 2014 Mar;76(3):884-7. doi: 10.1097/TA.0b013e3182aafdba.
• Reid F, Choi J, Williams M, Chan S. Prospective evaluation of the Sunshine Appendicitis Grading System score. ANZ J Surg. 2017 May;87(5):368-371. doi: 10.1111/ans.13271. Epub 2015 Sep 1.
• Jalava K, Sallinen V, Lampela H, Malmi H, Leppaniemi A, Mentula P. Role of delay and antibiotics on PERForation rate while waiting appendicECTomy (PERFECT): a protocol for a randomized non-inferiority trial. BJS Open. 2021 Sep 6;5(5):zrab089. doi: 10.1093/bjsopen/zrab089.

Helpful Links

• Link for calculation of Adult Appendicitis Score

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2020
• Primary Completion (Actual): January 23, 2023
• Study Completion (Actual): February 23, 2023

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 7, 2020

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 9, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Cecal Diseases; Intraabdominal Infections; Appendicitis; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antitubercular Agents; Metronidazole; Anti-Bacterial Agents; Antibiotics, Antitubercular; Cefuroxime; Cefuroxime axetil
• Other Study ID Numbers: HUS-PERFECT; 2019-002348-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No