Antibiotic Therapy Versus Appendectomy for Acute Appendicitis

A Prospective Randomized Multicentric Trial Comparing Amoxicillin/Clavulanate Potassium Therapy to Appendectomy for Acute Non Complicated Appendicitis

The purpose of the study is to demonstrate that antibiotic therapy is as safe and effective as appendectomy for the treatment of acute non complicated appendicitis. Two hundred fifty patients will be included in a prospective multicentric randomized trial. The primary endpoint is the rate of intra abdominal infections in both therapeutic strategies. Other criteria will be studied including duration of hospital stay and absence from work during a follow up period of one year, parietal and abdominal complications and recurrent appendicitis after antibiotic therapy.

Study Overview

• Status: Completed
• Conditions: Appendicitis
• Intervention / Treatment: Procedure: appendectomy; Drug: amoxicillin/clavulanate potassium

Detailed Description

Appendectomy is the most frequent intra-abdominal operation performed, accounting for the majority of admissions in a general surgery unit. Appendectomy has always been considered the cornerstone in the treatment of acute appendicitis.Nevertheless, the idea of a conservative treatment using antibiotics is not that recent. Current practices have proven the efficiency of antibiotic therapy in treating certain infectious abdominal conditions including: appendicular mass with or without periappendicular abscess and acute diverticulitis. This success has prompted the researchers to consider the exclusive use of antibiotic therapy in the treatment of non complicated appendicitis.

In patients with clinical suspicion of acute appendicitis (localized abdominal tenderness, inflammatory reaction...etc) a CT scan will be performed to confirm the diagnosis of non complicated appendicitis. This diagnosis is confirmed on the CT in the absence of any sign of either localized peritonitis, and/or perforation (extraluminal gas, appendicular abscess, or phlegmon).

After a thorough explanation of this study, the patient will be obliged to sign a written consent. Patients will be randomly assigned to either one of the two therapeutic modalities : an appendectomy,or an antibiotic treatment consisting of amoxicillin and clavulanate potassium.

This therapy will be continued until the normalisation of leucocytic count and C reactive protein are achieved. In order to demonstrate equivalent conclusive results comparing the two treatment modalities, the statistical consultant estimated the inclusion of at least 200 patients in the study. However, after considering the possible loss of a number of patients following their inclusion for a variety of reasons, it was decided that a total of 250 patients will be enrolled.

Rate of intra abdominal infections in both therapeutic strategies is the first endpoint to be compared. Duration of pain, diet, hospitalisation, absence from work will also be compared. In the group of patients treated by antibiotics, the rate of persistant and recurrent appendicitis after treatment will be evaluated. Recurrent appendicitis is not considered a complication as long as the recurrence of the appendicitis is uncomplicated. During the followup period of one year, long-term complications will be observed including: abdominal hernia, adhesive intestinal occlusion, and others.

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Clamart, France, 92141 cedex
    • Antoine Béclère Hospital - Department of Surgery
  • Creteil, France, 94
    • Henri Mondor Hospital
  • Paris, France, 75004
    • Hotel Dieu Hospital, Department of Digestive Surgery
  • Paris, France, 75014
    • Cochin Hospital, Department of Digestive Surgery
  • Paris, France, 75475
    • Lariboisière Hospital, Department of Digestive Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Before CT scanning

Inclusion Criteria:

• Clinical suspicion of appendicitis
• Age more than 18 years

Exclusion Criteria:

• Clinical signs of generalized peritonitis
• Previous take of antibiotics within the 5 days preceding the presentation
• Allergy or intolerance to lactamases and/or clavulanate potassium
• Corticosteroid or anticoagulant therapy
• Patient with a known inflammatory bowel disease (Crohn's disease or ulcerative colitis)
• Pregnant women
• Patient with iode allergy
• Renal insufficiency (creatinine > 200 )

CT scanning:

Inclusion Criteria:

• Appendix diameter > 6 mm

Exclusion Criteria:

• Appendix non visualised

• Signs of localized peritonitis:

  • extradigestive gas
  • fluid collection around the appendix
  • generalized intraperitoneal fluid

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; appendectomy, actual usual treatment	Procedure: appendectomy; ablation of the appendix by laparotomy or laparoscopy
Active Comparator: B; antibiotic therapy	Drug: amoxicillin/clavulanate potassium; 1 gramme, 3 times a day, intra venous initially and then orally for one or two weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
rate of intra abdominal infections in both therapeutic strategies	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
duration of pain	30 days
duration of hospitalisation	30 days
duration of absence from work	30 days
rate of wound infection	30 days
recurrence of appendicitis	12 months
rate of abdominal hernia	12 months
rate of adhesive intestinal occlusion	12 months
cost	30 days and 12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Corinne Vons, MD,PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Vons C, Barry C, Maitre S, Pautrat K, Leconte M, Costaglioli B, Karoui M, Alves A, Dousset B, Valleur P, Falissard B, Franco D. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial. Lancet. 2011 May 7;377(9777):1573-9. doi: 10.1016/S0140-6736(11)60410-8.

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: August 24, 2005
• First Submitted That Met QC Criteria: August 24, 2005
• First Posted (Estimate): August 26, 2005

Study Record Updates

• Last Update Posted (Estimate): February 12, 2009
• Last Update Submitted That Met QC Criteria: February 11, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Keywords: safety; randomized trial; treatment.; appendicitis.; adult.; antibiotic therapy.; CT scanning.
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Cecal Diseases; Intraabdominal Infections; Appendicitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: P020915; AOR 02063