Role of Delay and Antibiotics on Perforation Rate While Waiting Appendectomy

Study Overview
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Brief Summary
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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.

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

Conditions
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Appendicitis

Intervention / Treatment
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* Drug: Antibiotics, cefuroxime and metronidazole
* Drug: No antibiotics
* Other: urgent schedule
* Other: less urgent schedule


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients are randomized into two arms according to urgency and simultaneously each patient is randomized into two arms according to antibiotic treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Surgery within 8 hours, no antibiotics<br>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<br>* No antibiotics are given while waiting surgery.<br>Other: urgent schedule<br>* Patients can wait up to 8 hours for surgery.<br>|
| Experimental: Surgery within 24 hours, no antibiotics<br>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<br>* No antibiotics are given while waiting surgery.<br>Other: less urgent schedule<br>* Patients can wait up to 24 hours for surgery.<br>|
| Experimental: Surgery within 8 hours, antibiotics<br>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. | Drug: Antibiotics, cefuroxime and metronidazole<br>* Patient receives antibiotics while waiting appendectomy<br>Other: urgent schedule<br>* Patients can wait up to 8 hours for surgery.<br>|
| Experimental: Surgery within 24 hours, antibiotics<br>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. | Drug: Antibiotics, cefuroxime and metronidazole<br>* Patient receives antibiotics while waiting appendectomy<br>Other: less urgent schedule<br>* Patients can wait up to 24 hours for surgery.<br>|

What is the study measuring?
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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 |