Antibiotics vs. Placebo in Acute Uncomplicated Appendicitis

NCT03234296 | Enrolling By Invitation DMC

• 1 other identifier: APPAC III
• Study Type: interventional
• Target: 147
• 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" operation. At the same time other similar intra-abdominal infections, such as diverticulitis, are treated with antibiotics. Several studies have proved promising results of the safety and efficiency of antibiotics in the treatment of acute uncomplicated appendicitis. Our previous APPAC study, published in 2015 in the Journal of American Medical Association, also proved promising results with 73% of patients with CT-diagnosed uncomplicated appendicitis treated successfully with antibiotics within one-year follow-up. 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. Already in 1886 Fitz noted that 1/3 of patients in a large series of autopsies from the pre-appendicectomy era had evidence of prior appendices inflammation suggesting spontaneous resolution of acute appendicitis. Acute appendicitis is thought to be similar to acute diverticulitis ("left-sided appendicitis") and this similarity has been shown in epidemiological studies. Recent studies have shown no benefit of antibiotic treatment in the treatment of uncomplicated diverticulitis with outpatient management without antibiotics proving safe and well-functioning. The aim of this randomised double-blinded study is to compare antibiotic therapy with placebo to evaluate the role of antibiotic therapy in the resolution of CT-diagnosed uncomplicated acute appendicitis. The hypothesis is that antibiotic therapy is necessary in the treatment of acute uncomplicated appendicitis and that antibiotic therapy is superior to spontaneous resolution (placebo) with the primary endpoint evaluated at ten days after the intervention.

Conditions

Acute Appendicitis

Keywords

uncomplicated acute appendicitis; complicated acute appendicitis; antibiotic therapy; spontaneous resolution

Outcome Measures

Primary Outcomes (1)

• Success of the randomized treatment

  Resolution of acute appendicitis with study group treatment resulting in discharge from the hospital without the need for surgical intervention and treatment efficacy evaluated at ten days after initiation of the randomized treatment.

  10 days after treatment initiation

Secondary Outcomes (6)

• Late recurrence of appendicitis

  10 years

• Post-intervention complications

  10 years

• Hospital stay

  1 month

• VAS score (visual analogue score)

  10 years

• Sick leave

  1 month

Study Arms (2)

Antibiotic treatment

ACTIVE COMPARATOR

Ertapenem 1 g x 1 intravenously for 3 days, followed by per oral levofloxacin 500 mg x 1 and metronidazole 500 mg x 3 for 4 days, duration of treatment 7 days.

Drug: Ertapenem

Placebo

ACTIVE COMPARATOR

Intravenous placebo once a day for 3 days, followed by per oral placebo for 4 days with similar p.o. tablets as in the antibiotic group.

Other: Placebo

Interventions

Ertapenem DRUG

Intravenous antibiotic followed by per oral antibiotics

Also known as: Levofloxacin, Metronidazole

Antibiotic treatment

Placebo OTHER

Intravenous placebo followed by per oral placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Age between 18-60 years
• CT confirmed uncomplicated acute appendicitis
• Ability to give informed consent

You may not qualify if:

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

Sponsors & Collaborators

• Turku University Hospital: lead
• Tampere University Hospital: collaborator
• Kuopio University Hospital: collaborator
• Oulu University Hospital: collaborator
• Helsinki University Central Hospital: collaborator

Study Sites (1)

Turku University Hospital

Turku, Finland

Location

Related Publications (2)

• Salminen P, Sippola S, Haijanen J, Nordstrom P, Rantanen T, Rautio T, Sallinen V, Loyttyniemi E, Hurme S, Tammilehto V, Laukkarinen J, Savolainen H, Merilainen S, Leppaniemi A, Gronroos J. Antibiotics versus placebo in adults with CT-confirmed uncomplicated acute appendicitis (APPAC III): randomized double-blind superiority trial. Br J Surg. 2022 May 16;109(6):503-509. doi: 10.1093/bjs/znac086.

  PMID: 35576384 DERIVED

• Sippola S, Gronroos J, Sallinen V, Rautio T, Nordstrom P, Rantanen T, Hurme S, Leppaniemi A, Merilainen S, Laukkarinen J, Savolainen H, Virtanen J, Salminen P. A randomised placebo-controlled double-blind multicentre trial comparing antibiotic therapy with placebo in the treatment of uncomplicated acute appendicitis: APPAC III trial study protocol. BMJ Open. 2018 Nov 3;8(11):e023623. doi: 10.1136/bmjopen-2018-023623.

  PMID: 30391919 DERIVED

MeSH Terms

Conditions

Appendicitis

Interventions

Ertapenem; Levofloxacin; Metronidazole

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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blinded RCT, no care providers, patients or researchers are aware of the randomised treatment. Separate safety monitoring committee and preplanned interim analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary investigator

Model Details: Anticipated enrollment delays \> three alternate scenarios for sample size calculations, please see prtocol for details.

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: July 31, 2017
• Study Start: August 9, 2017
• Primary Completion: September 15, 2020
• Study Completion (Estimated): August 30, 2029
• Last Updated: November 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)