Optimizing the Antibiotic Treatment of Uncomplicated Acute Appendicitis

NCT03236961 | Active Not Recruiting

• 1 other identifier: APPAC II
• Study Type: interventional
• Target: 552
• Locations: 1 country
• Sites: 1

Brief 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 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. The aim of this randomized prospective study is to optimize antibiotic therapy for uncomplicated acute appendicitis by comparing different antibiotic regimens; intravenous antibiotic (ertapenem) followed by per oral antibiotic (levofloxacin and metronidazole) with only per oral antibiotics (moxifloxacin). Before randomization, the diagnosis of acute uncomplicated appendicitis is confirmed with a CT scan. The hypothesis is that broad-spectrum intravenous antibiotics requiring additional hospital resources are not necessary for the treatment of uncomplicated acute appendicitis and that per oral mono therapy is non-inferior to the combination of intravenous and per oral antibiotic therapy.

Conditions

Acute Appendicitis

Keywords

uncomplicated acute appendicitis; complicated acute appendicitis; antibiotic therapy

Outcome Measures

Primary Outcomes (1)

• Treatment success

  The resolution of acute uncomplicated appendicitis with allocated antibiotic treatment. Treatment success is defined as discharge from the hospital without the need for surgical intervention after the primary hospitalisation and no recurrent appendicitis during one-year follow-up.

  1 year

Secondary Outcomes (6)

• Late recurrence of appendicitis after antibiotic treatment

  1 year

• Duration of hospital stay

  1 month

• Post-intervention complications

  10 years

• VAS pain score (visual analogue score)

  10 years

• Sick leave

  1 month

Study Arms (2)

Intravenous & per oral antibiotics

ACTIVE COMPARATOR

Ertapenem 1 g x 1 for two days i.v. followed by p.o. levofloxacin 500 mg x 1 and metronidazole 500 mg x 3 for 5 days, duration of treatment one week.

Drug: Ertapenem

Per oral antibiotics

ACTIVE COMPARATOR

Moxifloxacin 400 mg x 1 foe seven days, duration of treatment one week.

Drug: Moxifloxacin

Interventions

Ertapenem DRUG

I.v. ertapenem 1 g for 2 days followed by p.o. levofloxacin 500 mg x1 and metronidazole 500 mg x 3 for 5 days

Also known as: Levofloxacin, Metronidazole

Intravenous & per oral antibiotics

Moxifloxacin DRUG

P.o. moxifloxacin 400 mg x1 for 7 days

Per oral antibiotics

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60 years
• CT confirmed uncomplicated acute appendicitis
• Ability to give consent to participate in the study

You may not qualify if:

• Age under 18 years or over 60 years
• Pregnancy or lactation
• Allergy to contrast media or iodine
• Allergy or contraindication to antibiotic therapy
• Renal insufficiency
• Metformin medication
• Severe systemic illness (for example malignancy, medical condition requiring immunosuppressant medication)
• CT confirmed complicated acute appendicitis
• Inability to co-operate and give informed consent

Sponsors & Collaborators

• Turku University Hospital: lead
• Oulu University Hospital: collaborator
• Tampere University Hospital: collaborator
• Kuopio University Hospital: collaborator
• Mikkeli Central Hospital: collaborator
• Lapland Central Hospital: collaborator
• Jyväskylä Central Hospital: collaborator
• Satakunta Central Hospital: collaborator
• Seinajoki Central Hospital: collaborator

Study Sites (1)

Turku University Hospital

Turku, Finland

Location

Related Publications (4)

• Selanne L, Hurme S, Sippola S, Rautio T, Nordstrom P, Rantanen T, Pinta T, Ilves I, Mattila A, Savela EL, Rintala J, Paajanen H, Gronroos J, Haijanen J, Salminen P. Prognostic factors associated with primary non-responsiveness to antibiotics and appendicitis recurrence for CT-diagnosed uncomplicated acute appendicitis: secondary analysis of two randomized clinical trials. Br J Surg. 2025 Jul 3;112(7):znaf143. doi: 10.1093/bjs/znaf143.

  PMID: 40741675 DERIVED

• Selanne L, Haijanen J, Sippola S, Hurme S, Rautio T, Nordstrom P, Rantanen T, Pinta T, Ilves I, Mattila A, Rintala J, Marttila H, Merilainen S, Laukkarinen J, Savela EL, Paajanen H, Gronroos J, Salminen P. Three-Year Outcomes of Oral Antibiotics vs Intravenous and Oral Antibiotics for Uncomplicated Acute Appendicitis: A Secondary Analysis of the APPAC II Randomized Clinical Trial. JAMA Surg. 2024 Jul 1;159(7):727-735. doi: 10.1001/jamasurg.2023.5947.

  PMID: 38630471 DERIVED

• Sippola S, Haijanen J, Gronroos J, Rautio T, Nordstrom P, Rantanen T, Pinta T, Ilves I, Mattila A, Rintala J, Loyttyniemi E, Hurme S, Tammilehto V, Marttila H, Merilainen S, Laukkarinen J, Savela EL, Savolainen H, Sippola T, Aarnio M, Paajanen H, Salminen P. Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis: The APPAC II Randomized Clinical Trial. JAMA. 2021 Jan 26;325(4):353-362. doi: 10.1001/jama.2020.23525.

  PMID: 33427870 DERIVED

• Haijanen J, Sippola S, Gronroos J, Rautio T, Nordstrom P, Rantanen T, Aarnio M, Ilves I, Hurme S, Marttila H, Virtanen J, Mattila A, Paajanen H, Salminen P; APPAC study group. Optimising the antibiotic treatment of uncomplicated acute appendicitis: a protocol for a multicentre randomised clinical trial (APPAC II trial). BMC Surg. 2018 Dec 17;18(1):117. doi: 10.1186/s12893-018-0451-y.

  PMID: 30558607 DERIVED

MeSH Terms

Conditions

Appendicitis

Interventions

Ertapenem; Levofloxacin; Metronidazole; Moxifloxacin

Condition Hierarchy (Ancestors)

Intraabdominal Infections; Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Cecal Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Paulina Salminen, MD, PhD

  Turku University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: August 2, 2017
• Study Start: April 3, 2017
• Primary Completion: November 27, 2018
• Study Completion (Estimated): April 1, 2029
• Last Updated: November 12, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)