Acute Appendicitis and Microbiota - Etiology of Appendicitis and Antibiotic Therapy Effects

Summary

Appendicectomy has been the treatment of acute appendicitis for over a hundred years. Appendicectomy, however, includes operative and postoperative risks despite being a routine procedure. Several studies have proved promising results of the safety and efficiency of antibiotics in the treatment of acute uncomplicated appendicitis. The previous APPAC study by the investigators, published in 2015 in the Journal of American Medical Association, also proved promising results with 73% of patients with uncomplicated appendicitis treated successfully with antibiotics. None of the patients initially treated with antibiotics that later had appendectomy had major complications. The results of the APPAC trial suggest that CT proven uncomplicated acute appendicitis is not a surgical emergency and antibiotic therapy is a safe first-line treatment option. Reducing unnecessary appendectomies has also been shown to lead to significant economic savings. On the other hand, antibiotic therapies have been shown to have an effect on the normal gut microbiota and are considered an increasing global health threat underlining the importance of evaluating both short- and long-term effects of the antimicrobial treatment in old and new indications.

The aims of this randomized prospective study are:

1. To evaluate the possible role and differences in the microbiological etiology of complicated and uncomplicated appendicitis.
2. To determine the effects of both antibiotic and placebo treatment on the composition of gut microbiota, and to evaluate how it recovers after the appendicitis-related antimicrobial treatment (AMT)
3. To evaluate the effects of the duration of the hospital stay on the AMR reservoir of the gut microbiota.

Conditions

• Acute Appendicitis

Interventions

DRUG

Ertapenem followed by levofloxacin and metronidazole

Ertapenem 1 g i.v. daily for either 2 days (MAPPAC + APPAC II patients) or 3 days (MAPPAC + APPAC III) followed by p.o. levofloxacin 500 mg x 1 + metronidazole 500 mg x 3 for either 5 days (APPAC II + MAPPAC) or 4 days (APPAC III + MAPPAC)

DRUG

Moxifloxacin

Moxifloxacin 400 mg once a day for seven days (APPAC II + MAPPAC)

PROCEDURE

Appendectomy

Primarily laparoscopic appendectomy for either complicated acute appendicitis or uncomplicated acute appendicitis (refusing to participate in APPAC II or III trials or recurrent acute appendicitis).

OTHER

Placebo

Placebo i.v. once a day for three days (APPAC III + MAPPAC) followed by placebo capsules three times a day for four days.

Sponsors & Collaborators

• Tampere University Hospital

  collaborator OTHER

• Oulu University Hospital

  collaborator OTHER

• Kuopio University Hospital

  collaborator OTHER

• Helsinki University Central Hospital

  collaborator OTHER

• Jyväskylä Central Hospital

  collaborator OTHER

• Turku University Hospital

  lead OTHER_GOV

Principal Investigators

• Paulina Salminen, MD, PhD · Turku University Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-04-04

Primary Completion

2022-12-31

Completion

2025-12-31

Countries

• Finland

Study Locations