Antibiotic Treatment Alone for Acute Simple Appendicitis in Children

Antibiotic Treatment Alone for Acute Simple Appendicitis in Children; a Prospective Cohort Study Part of the Antibiotic Versus Primary Appendectomy in Children (APAC) Trial

Appendectomy for acute appendicitis has recently been questioned as being the only correct treatment for appendicitis. Appendectomy has been reported to have significant early and late morbidity. This can be avoided with antibiotic treatment alone. Moreover, better quality of life and lower costs have been associated with antibiotic treatment alone. Five clinical trials in selected patients (males, older than 18 years) comparing appendectomy and antibiotic treatment alone as primary mode of treatment found that antibiotic treatment alone is safe and effective in 48-95% of the patients Conclusive evidence with regard to the efficacy of antibiotic treatment alone in children with proven acute appendicitis however is lacking. We propose a prospective cohort study to answer the following questions:

Study Overview

• Status: Completed
• Conditions: Appendicitis
• Intervention / Treatment: Drug: Antibiotic treatment alone; Procedure: Appendectomy

Detailed Description

Primary Objective:

What is the complication rate of the initial antibiotic treatment strategy (IATS) for acute simple appendicitis (radiological proven) in children aged 7-17 years old?

Secondary Objective:

What is the complication rate of the direct appendectomy treatment strategy (DATS) for acute simple appendicitis (radiological proven) in children aged 7-17 years old?

Study design:

Prospective multi-centre pilot cohort study.

Study population:

Children (7-17years old) with radiologically proven simple appendicitis.

Intervention:

Initial antibiotic treatment strategy (IATS): Intravenous administration of amoxicillin/clavulanic acid 25/2.5mg 6-hourly (total 100/10 mg/kg daily; maximum 6000/600mg a day) and gentamicin 7mg/kg once daily will be given for 48 hours. If possible the antibiotics will be switched to oral amoxicillin/clavulanic acid 50/12.5 mg/kg 8-hourly (max 1500/375mg a day) for in total 7 days. If after 72 hours, the patient does not meet the predefined criteria, an appendectomy will be performed.

Control group:

The control group will consist of patients, who do not want the antibiotic treatment. Their medical files will be monitored prospectively. In addition they will be scheduled for an extra outpatient clinic follow up (8 weeks after discharge), extra telephone contact one year after discharge and asked to fill out quality of life questionnaires.

Primary parameters/endpoints:

Safety of initial antibiotic treatment defined as:

Occurrence of major complications, such as:

A. Anaphylactic shock and other allergic reaction to antibiotics administered b. Recurrent appendicitis within 8 weeks c. Recurrent appendicitis within one year after discharge d. Development of perforated appendicitis e. Occurrence of major complaints after delayed appendectomy such as intra-abdominal abscess (IAA), stumpleakage, superficial site infection (SSI), anaesthesia related complications, secondary bowel obstruction (SBO), re-admission, need for re-intervention f. Re-admission g. Re-intervention other than delayed appendectomy

Secondary outcome parameters Major complications associated with appendectomy

1. Stumpleakage
2. Intra-abdominal abscess (IAA)
3. Secondary bowel obstruction (SBO)
4. Superficial site infection (SSI)
5. Need for secondary operation
6. Need for other re-intervention
7. Re-admission
8. Anaesthesia related complication
9. Pneumonia

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

1. Risks of participation: Need for delayed operation, recurrent appendicitis. Risks that are also present in case of non-participation: Allergic reaction to antibiotics, known appendectomy associated complications.
2. Burden of participation: Extra admission day (in comparison with appendectomy), ultrasonography after 48 hours (extra procedure), outpatient follow up (two extra visits), filling out QOL questionnaires. Burden also present in case of non-participation: Intravenous access (normal procedure), daily blood samples (normal procedure). Regarding the control group, the burden will consist of an extra outpatient clinic follow up (8 weeks after discharge), extra telephone contact one year after discharge and fill out quality of life questionnaires.
3. Benefit of participation: Avoidance of surgery and its related early and late morbidity, potential better quality of life.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Almere, Netherlands
    • Flevoziekenhuis
  • Amsterdam, Netherlands
    • VU University Medical Center
  • Amsterdam, Netherlands
    • Academic Medical Center of Amsterdam
  • Beverwijk, Netherlands
    • Red Cross Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 7-17 years

2. Radiologically confirmed simple appendicitis, defined as:

   a. Clinical findings: i. Unwell, but not generally ill ii. Localized tenderness in the right iliac fossa region iii. Normal/hyperactive bowel sounds iv. No guarding v. No mass palpable b. Ultrasonography: i. Incompressible appendix with an outer diameter of ≥6 mm ii. Hyperaemia within the appendiceal wall iii. Without fecalith iv. Infiltration of surrounding fat v. No signs of perforation vi. No signs of intra abdominal abscess/phlegmon

Exclusion criteria:

1. Patients with severe general illness at time of presentation:

   1. Generalized peritonitis defined as:

      Diffuse inflammation of the peritoneum with clinical signs consisting of increasing abdominal pain, generalized tenderness, diffuse abdominal rigidity, sinus tachycardia, signs of paralytic ileus

   2. Severe sepsis or septic shock, as defined by the international paediatric sepsis consensus conference [39]. See attachment 1.
   3. Signs of complex appendicitis
2. Children with a fecalith on ultrasonography.

3. Patients with serious associated conditions or malformations such as:

   1. Congenital or acquired cardiac or pulmonary disease with significant hemodynamic consequences
   2. Immunodeficiency
   3. Malignancy
   4. Homozygous sickle cell disease
   5. Metabolic disorders
4. Patient with documented type 1 allergy to the antibiotics used

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antibiotic treatment alone; Intravenous administration: Amoxicillin/clavulanic acid 100/10 mg/kg 6-hourly Gentamicin 7mg/kg once daily Oral administration of: Amoxicillin/clavulanic acid 50/12.5 mg/kg/day (in three doses)	Drug: Antibiotic treatment alone; Amoxicillin/clavulanic acid 100/10 mg/kg 6-hourly Gentamicin 7 mg/kg once daily At least 48 hours intravenous administration, in total seven days of antibiotics Oral amoxicillin/clavulanic acid 50/12.5mg/kg
Active Comparator: Appendectomy; Routine appendectomy either laparoscopic or open depending on the surgeon's preference	Procedure: Appendectomy; Appendectomy either open or laparoscopic depending on the surgeon's preference

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of initial antibiotic treatment strategy	Occurrence of major complications, such as: A. Anaphylactic shock and other allergic reaction to antibiotics administered b. Recurrent appendicitis within 8 weeks c. Recurrent appendicitis within one year after discharge d. Development of perforated appendicitis e. Occurrence of major complaints after delayed appendectomy such as intra-abdominal abscess (IAA), stumpleakage, superficial site infection (SSI), anaesthesia related complications, secondary bowel obstruction (SBO), re-admission, need for re-intervention f. Re-admission g. Re-intervention other than delayed appendectomy	0-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the direct appendectomy treatment strategy	Major complications associated with appendectomy; Stumpleakage; Intra-abdominal abscess (IAA); Secondary bowel obstruction (SBO); Superficial site infection (SSI); Need for secondary operation; Need for other re-intervention; Re-admission; Anaesthesia related complication; Pneumonia	0-12 months

Collaborators and Investigators

• Sponsor: Ramon R. Gorter
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); St. Antonius Hospital; Flevoziekenhuis; Red Cross Hospital Beverwijk
• Investigators: Principal Investigator: Ramon R Gorter, MD, Amsterdam UMC, location VUmc; Study Chair: Hugo A Heij, MD, PhD, Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: April 18, 2011
• First Submitted That Met QC Criteria: May 18, 2011
• First Posted (Estimate): May 19, 2011

Study Record Updates

• Last Update Posted (Estimate): January 13, 2017
• Last Update Submitted That Met QC Criteria: January 12, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Children; Antibiotic treatment; Non perforated appendicitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Cecal Diseases; Intraabdominal Infections; Appendicitis; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: KCA2011/APAC