The NOTA study: non-operative treatment for acute appendicitis: prospective study on the efficacy and safety of antibiotic treatment (amoxicillin and clavulanic acid) in patients with right sided lower abdominal pain

Abstract

Background

Case control studies that randomly assign patients with diagnosis of acute appendicitis to either surgical or non-surgical treatment yield a relapse rate of approximately 14% at one year. It would be useful to know the relapse rate of patients who have, instead, been selected for a given treatment based on a thorough clinical evaluation, including physical examination and laboratory results (Alvarado Score) as well as radiological exams if needed or deemed helpful. If this clinical evaluation is useful, the investigators would expect patient selection to be better than chance, and relapse rate to be lower than 14%. Once the investigators have established the utility of this evaluation, the investigators can begin to identify those components that have predictive value (such as blood analysis, or US/CT findings). This is the first step toward developing an accurate diagnostic-therapeutic algorithm which will avoid risks and costs of needless surgery.

Methods/design

This will be a single-cohort prospective observational study. It will not interfere with the usual pathway, consisting of clinical examination in the Emergency Department (ED) and execution of the following exams at the physician's discretion: full blood count with differential, C reactive protein, abdominal ultrasound, abdominal CT. Patients admitted to an ED with lower abdominal pain and suspicion of acute appendicitis and not needing immediate surgery, are requested by informed consent to undergo observation and non operative treatment with antibiotic therapy (Amoxicillin and Clavulanic Acid). The patients by protocol should not have received any previous antibiotic treatment during the same clinical episode. Patients not undergoing surgery will be physically examined 5 days later. Further follow-up will be conducted at 7, 15 days, 6 months and 12 months. The study will conform to clinical practice guidelines and will follow the recommendations of the Declaration of Helsinki. The protocol was approved on November 2009 by Maggiore Hospital Ethical Review Board (ID CE09079).

Trial Registration

ClinicalTrials.gov identifier: NCT01096927.

Article summary

Article focus

• Acute appendicitis can have severe complications including perforation and generalised peritonitis.

• The appendix is found to be free of disease in 15–30% of appendectomies.

• As surgery carries various risks, conservative non-surgical treatment with antibiotics for suspected appendix inflammation may avoid needless surgery, in particular as the relapse rate is low and the rate of complications is similar.

Key messages

• Case control studies that randomly assign patients with acute appendicitis to either surgical or non-surgical treatment show a relapse rate of approximately 14% at 1 year.

• The relapse rate of patients who are treated based on a thorough clinical evaluation should be below 14%.

• Once factors predictive of outcome and/or the need of surgery are identified, an accurate diagnostic-therapeutic algorithm which will help avoid the risks and costs of needless surgery can be developed.

Strengths and limitations of this study

• This non-randomised controlled study will evaluate the effectiveness and short and long term outcomes of non-operative antibiotic treatment of acute appendicitis.

• Amoxicillin and clavulanic acid are common and easily managed low cost drugs, available both for intravenous and oral use.

• Better analysis of clinical data might lead to better decision-making in patients with right iliac fossa pain and suspected acute appendicitis.

• The study also aims to evaluate the Alvarado score, which is used to diagnose acute appendicitis and discriminate patients needing immediate surgery from patients who may safely undergo observation and antibiotic treatment.

• A large sample of patients undergoing non-operative antibiotic treatment will allow a statistically powerful evaluation of safety, efficacy and cost.

• An additional objective is to identify clinical, laboratory and imaging findings that are predictive of failure of conservative treatment and/or relapse of appendicitis and need for appendectomy within 1 year.

• As efficacy can not be reliably determined in the absence of a control group, a case series observation determining ‘efficacy’ has limited value.

• The Alvarado score is used to separate those with acute appendicitis from those with similar symptoms but no appendicitis and there is no evidence that this score can identify those who would benefit from antibiotic treatment.