Role of Delay and Antibiotics on Perforation Rate While Waiting Appendectomy

Phase 4

Completed

• Conditions: Appendicitis
• Interventions: Drug: Antibiotics, cefuroxime and metronidazole; Drug: No antibiotics; Other: urgent schedule; Other: less urgent schedule

• Registration Number: NCT04378868
• Lead Sponsor: Helsinki University Central Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-04-29
• Study First Submitted QC: 2020-05-04
• Study First Posted: 2020-05-07
• Study Start: 2020-05-18
• Primary Completion: 2023-01-23
• Study Completion: 2023-02-23
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-09
• Last Update Posted: 2023-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1800

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Surgery within 8 hours, antibiotics	urgent schedule	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.
Surgery within 8 hours, no antibiotics	urgent schedule	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.
Surgery within 24 hours, no antibiotics	less urgent schedule	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.
Surgery within 8 hours, antibiotics	Antibiotics, cefuroxime and metronidazole	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.
Surgery within 24 hours, antibiotics	less urgent schedule	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.
Surgery within 8 hours, no antibiotics	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.
Surgery within 24 hours, no antibiotics	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.
Surgery within 24 hours, antibiotics	Antibiotics, cefuroxime and metronidazole	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.

Primary Outcome Measures

Name	Time	Method
Complicated appendicitis	during surgery	Surgical finding is complicated appendicitis (AAST Grade III-V)

Secondary Outcome Measures

Name	Time	Method
Postoperative complications	30 days from surgery	complications are defined according to Clavien-Dindo classification
Gangrenous or perforated appendicitis according to pathological examination.	3 week after surgery	All specimens are sent to pathological examination and all pathological reports are reviewed
Sunshine Appendicitis Grading System Score classification	during surgery	Sunshine Appendicitis Grading System Score (range 0-4) for appendicitis. Higher score represents worse outcome
Conversions of laparoscopic surgeries to open surgery	during the the first operation for acute appendicitis	All surgeries are started as laparoscopic surgery. Conversion means that operation is converted to open surgery during the same operation.
Time of hospital stay	30 days from surgery	Time in hours from randomization to discharge from hospital
Pain measured by numeric rating scale while waiting surgery	up to 36 hours	Pain is measured by numeric rating scale (NRS) every hour by patient, and area under NRS represents overall pain.
Surgical site infections (SSI) and positive blood cultures	within 30 days from randomization	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.

Trial Locations

Locations (2)

HUS, Meilahti Hospital; 🇫🇮 Helsinki, Finland

HUS, Jorvi Hospital; 🇫🇮 Espoo, Finland