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Non Operative Treatment for Acute Appendicitis (NOTA)

M

Maggiore Bellaria Hospital, Bologna

Status and phase

Completed
Phase 4

Conditions

Acute Appendicitis
Right Iliac Fossa Pain
Lower Abdominal Pain

Treatments

Drug: Amoxicillin and Clavulanic Acid

Study type

Interventional

Funder types

Other

Identifiers

NCT01096927
CE 09079

Details and patient eligibility

About

Case control studies that randomly assign patients 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 (all characteristics forming the 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 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 chemistry analysis, or CT findings). This is the first step toward developing an accurate diagnostic-therapeutic algorithm which will avoid the risks and costs of needless surgery.

This will be a single-cohort prospective interventional study. It will not interfere with the usual procedures, consisting of clinical examination in the Emergency Department (ED) and execution of the following exams at the physician's discretion: complete blood count with differential, C reactive protein, abdominal ultrasound, abdominal CT. Patients admitted to Emergency Department with Lower Abdominal and suspicion of Acute Appendicitis 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. During this follow-up visit, the patient will be given information about the study, will be invited to participate, and will be asked to sign an informed consent form. If the patient is under the age of 18 years, consent will be obtained from a parent or other legal guardian.

Telephone (or email) follow-ups will be conducted at 15 days, 6 months, and 12 months (see attached schedule) to monitor the state of the illness.

Full description

Background: Acute appendicitis is one of the most common urgent conditions seen in general surgery practice. Complications can be severe and include perforation and generalized peritonitis. Traditionally, surgical appendectomy has been the primary treatment, even in cases of unconfirmed diagnosis, given the low incidence of major complications. In 15-30% of cases, in fact, the appendix is found to be free of disease upon resection. This procedure, however, is not without risk. It is associated with surgical wound infection, intestinal obstruction due to adhesions, pneumonia, and tubal infertility in females. For this reason, the possibility of using conservative treatment merits investigation. There is considerable debate regarding the utility of conservative treatment over surgical treatment in some cases of acute appendicitis, as few studies have addressed this issue to date. If deemed useful, it will become of utmost importance to make an accurate diagnosis and assessment in every patient in order to select the most appropriate treatment.

Hansson et al conducted a randomized clinical trial investigating the efficacy of conservative treatment compared to surgery for acute appendicitis. They reported that conservative treatment with antibiotics was efficacious in 91% of cases, with a 14% relapse rate at 12 month follow-up. One third of relapses occurred within the first 10 days of hospital discharge, while most of the remaining two thirds occurred between 3 and 16 months following discharge. The rates of minor complications such as diarrhea, vomiting, and nosocomial infections were similar among patients treated conservatively and those treated surgically. The incidence of major complications such as appendiceal abscess, paralytic ileus and pulmonary embolism, however, was significantly higher in those treated surgically (p<0.05).

A recent prospective randomized study conducted by Ajaz and colleagues compared antibiotic therapy to appendectomy in acute appendicitis. The authors reported that conservative treatment was not only safe and efficacious, but caused the patients less pain than did surgery, reducing the need for analgesic therapy (p<0.001). Ten percent of conservatively treated patients relapsed within 12 months of discharge.

A multicenter randomized trial conducted in Sweden yielded similar results: the rate of relapse in antibiotic treated patients was 14% at one year after discharge. Interestingly, this was equal to the rate of post-operative complications in patients treated surgically.

Based on these reports, conservative treatment seems to represent a valid therapeutic approach to acute appendicitis. Relapse rate is low and comparable to the rate of surgical complications.

Rationale: Case control studies that randomly assign patients 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 (all characteristics forming the 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 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 chemistry analysis, or CT findings). This is the first step toward developing an accurate diagnostic-therapeutic algorithm which will avoid the risks and costs of needless surgery.

Study Description: This will be a single-cohort prospective interventional study. It will not interfere with the usual procedures, consisting of clinical examination in the Emergency Department (ED) and execution of the following exams at the physician's discretion: complete blood count with differential, C reactive protein, abdominal ultrasound, abdominal CT. Patients admitted to Emergency Department with Lower Abdominal and suspicion of Acute Appendicitis 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. During this follow-up visit, the patient will be given information about the study, will be invited to participate, and will be asked to sign an informed consent form. If the patient is under the age of 18 years, consent will be obtained from a parent or other legal guardian.

Telephone (or email) follow-ups will be conducted at 15 days, 6 months, and 12 months (see attached schedule) to monitor the state of the illness. The patient will be asked if he/she has undergone surgery since the first visit (5 days post-ED). If not, the patient will be asked:

  1. has your illness improved, stayed the same, or worsened since its onset?
  2. have you done any further tests or had additional doctor's visits for your illness?
  3. after your initial emergency department visit, how much time did it take to return to your normal activities (physical activity, work, etc)? In the case of patients under the age of 18 years, the phone interview will be conducted with a parent or legal guardian.

Study Objectives:

Main Objective: Evaluate the outcome of patients treated conservatively, assessing the reliability of the initial clinical evaluation in predicting which conservatively-treated patients should have treated surgically.

Primary Outcomes are the following:

  1. Short Term Efficacy of Antibiotic Treatment: Failure of the conservative treatment with antibiotic within the period of the Amoxicillin + Clavulanic Acid therapy (7 days), defined as readmission for abscence of clinical improvement and/or worsening abdominal pain and/or localized/diffuse peritonitis
  2. Long Term Efficacy of Antibiotic Treatment: Efficacy of antibiotic therapy for acute appendicitis defined as incidence of recurrences of clinical episodes of appendicitis up to 1 year follow up
  3. Long Term Efficacy of Antibiotic Treatment (NO need for surgery): Efficacy of antibiotic therapy for acute appendicitis defined as definite improvement without need for surgery within 1 year follow up
  4. Safety of Antibiotic treatment: Major side effects/complications drug/treatment-related (i.e. Allergy or other complications treatment related such as abscess formation)

Secondary Outcomes are:

  1. Minor Complications: Minor side effects/complications drug/treatment-related (i.e. bloating, diarrhea, gas, headache, heartburn, nausea, and vomiting)
  2. Abdominal Pain after discharge: Assessment of abdominal pain / discomfort evaluated by mean of Numerical rating scale (NRS)
  3. Length of Hospital stay: Length of clinical observation as inpatient
  4. Outpatient clinic checkup: Number of follow up appointments scheduled in outpatient clinic
  5. Sick Leave: Number of days of sick leave needed by the patient
  6. Cost analysis: Analysis of the costs, including Antibiotic course, Length of Hospital Stay, Outpatient Clinic follow up appointments, sick leave days

Additional Objective: Identify clinical, laboratory or imaging findings that are predictive of relapse and need for appendectomy.

Study Design: Single cohort prospective interventional study. No experimental interventions or treatments will be employed beyond routine clinical care.

Inclusion Criteria: Any patient, male or female, above the age of 14 years (non-pediatric), who returns for the follow-up visit 5 days after the ED visit and consents participation between January 1, 2010 and December 31, 2010.

The investigators estimate a sample size of 160, the number of patients with suspected acute appendicitis we typically receive yearly in the ED.

Means of follow-up assessment: telephone interview (or e-mail)

Enrollment

160 patients

Sex

All

Ages

14+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Age >14 years

  2. Lower / RIF Abdominal Pain

  3. Clinical Suspicion of Acute Appendicitis:

    i.e.

    • Alvarado Score 5-6 (equivocal for acute appendicitis)
    • Alvarado Score 7-8 (probably appendicitis)
    • Alvarado Score 9-10 (highly likely appendicitis)
  4. Informed consent (patient or legal representative)

Exclusion criteria

  1. Diffuse peritonitis
  2. Antibiotic (Penicillin) documented allergy
  3. Ongoing previously started antibiotic therapy
  4. Previous appendectomy
  5. Positive pregnancy test
  6. IBD history or suspicion of IBD recrudescence

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

160 participants in 1 patient group

Non operative Treatment group
Experimental group
Description:
Patients with Lower Abdominal and suspected Acute Appendicitis, treated non-operatively with 7 days antibiotic therapy (Amoxicillin and Clavulanic Acid)
Treatment:
Drug: Amoxicillin and Clavulanic Acid

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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