Antibiotic Treatment Alone for Acute Simple Appendicitis in Children

Appendicitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01356641
• Other study ID #: KCA2011/APAC
• Status: Completed
• Phase: N/A
• First received: April 18, 2011
• Last updated: January 12, 2017
• Start date: September 2012
• Est. completion date: January 2017

Study information

• Verified date: January 2017
• Source: VU University of Amsterdam
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Appendicitis

Intervention

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

Procedure:
• Appendectomy
Appendectomy either open or laparoscopic depending on the surgeon's preference

Locations

Country	Name	City	State
Netherlands	Flevoziekenhuis	Almere
Netherlands	Academic medical center of Amsterdam	Amsterdam
Netherlands	VU University medical center	Amsterdam
Netherlands	Red Cross Hospital	Beverwijk

Sponsors (5)

Lead Sponsor	Collaborator
Ramon R. Gorter	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Flevoziekenhuis, Red Cross Hospital Beverwijk, St. Antonius Hospital

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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