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Antibiotic Treatment Alone for Acute Simple Appendicitis in Children

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by VU University of Amsterdam
Sponsor:
Collaborators:
Red Cross Hospital Beverwijk
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
St. Antonius Hospital
Flevoziekenhuis, Almere
Information provided by (Responsible Party):
Ramon R. Gorter, VU University of Amsterdam
ClinicalTrials.gov Identifier:
NCT01356641
First received: April 18, 2011
Last updated: July 23, 2013
Last verified: July 2013
  Purpose

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. The investigators propose a pilot study to determine if antibiotic treatment alone is safe and effective for children with radiologically diagnosed simple appendicitis as well as if a non inferiority randomized controlled trial investigating this treatment strategy is currently feasible.


Condition Intervention
Appendicitis
Drug: Antibiotic treatment alone

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by VU University of Amsterdam:

Primary Outcome Measures:
  • Safety of antibiotic treatment alone [ Time Frame: 0-12 months ] [ Designated as safety issue: Yes ]

    Safety of antibiotic treatment defined as:

    Failure of antibiotic treatment alone defined as:

    Need for secondary operation due to lack of response to antibiotic treatment Occurrence of major complications defined as anaphylactic shock and other allergic reaction to antibiotics administered Recurrent appendicitis within 8 weeks Recurrent appendicitis within one year after discharge Occurrence of major complaints after secondary appendectomy Recurrent appendicitis within one year.


  • Feasibility [ Time Frame: Time of presentation ] [ Designated as safety issue: No ]
    Signed informed consent / number of eligible patients


Secondary Outcome Measures:
  • Duration of hospital stay [ Time Frame: Discharge date Expected 1 week ] [ Designated as safety issue: No ]
    Day 1 until discharge. An expected average of 1 week

  • Time to resume normal activities [ Time Frame: 0-6 months ] [ Designated as safety issue: No ]
    Ability of children to perform their normal daily activities( Sick leave from school)

  • Days of intravenous antibiotics [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Number of days with intravenous antibiotics. Approximately 48 hours


Estimated Enrollment: 50
Study Start Date: August 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

Objective:

  1. Is a non inferiority randomised controlled trial to determine the effectiveness and safety of antibiotic treatment alone versus appendectomy in children aged 7-17 with proven appendicitis (simple and complex) feasible?
  2. Is antibiotic treatment for simple appendicitis in children aged 7-17 years safe?

Study design:

Prospective multi-centre pilot cohort study.

Study population:

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

Intervention:

Intravenous administration of amoxicillin/clavulanic acid 25/2.5mg 6-hourly (total 100/10 mg/kg daily) 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 for in total 7 days. If after 72 hours, the patient does not meet the predefined criteria, an appendectomy will be performed.

Main study parameters/endpoints:

  1. Number of patients willing to participate in this study, defined as signed informed consent / number of patients eligible for inclusion.
  2. Safety of antibiotic treatment defined as:

    1. Failure of antibiotic treatment alone defined as:

      Need for secondary operation due to lack of response to antibiotic treatment

    2. Occurrence of major complications defined as anaphylactic shock and other allergic reaction to antibiotics administered
    3. Recurrent appendicitis within 8 weeks
    4. Recurrent appendicitis within one year after discharge
    5. Occurrence of major complaints after secondary appendectomy

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

  1. Risks of participation: Need for 'secondary' operation, recurrent appendicitis. Risks that are also present in case of non-participation: Allergic reaction to antibiotics,
  2. Burden of participation: 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),
  3. Benefit of participation: Avoidance of surgery and its related early and late morbidity, potential better quality of life.
  Eligibility

Ages Eligible for Study:   7 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01356641

Contacts
Contact: Ramon R Gorter, MD 020-4442424 rr.gorter@vumc.nl
Contact: H A Heij, MD PhD 0205665693 ha.heij@vumc.nl

Locations
Netherlands
Academic medical center of Amsterdam Recruiting
Amsterdam, Netherlands
Contact: H. A. Heij, MD, PhD    0205665693    h.a.heij@amc.uva.nl   
Principal Investigator: H A Heij, MD PhD         
VU University medical center Recruiting
Amsterdam, Netherlands
Contact: Ramon R Gorter, MD    0204442424    rr.gorter@vumc.nl   
Principal Investigator: Ramon R Gorter, MD         
Red Cross Hospital Recruiting
Beverwijk, Netherlands
Contact: H A Cense, MD PhD    0251265555    hcense@rkz.nl   
Principal Investigator: H A Cense, MD PhD         
Sponsors and Collaborators
Ramon R. Gorter
Red Cross Hospital Beverwijk
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
St. Antonius Hospital
Flevoziekenhuis, Almere
Investigators
Principal Investigator: Ramon R Gorter, MD VU University Medical Center
Study Chair: Hugo A Heij, MD, PhD VU University Medical Center
  More Information

No publications provided

Responsible Party: Ramon R. Gorter, MD, PhD candidate, VU University of Amsterdam
ClinicalTrials.gov Identifier: NCT01356641     History of Changes
Other Study ID Numbers: KCA2011/APAC
Study First Received: April 18, 2011
Last Updated: July 23, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by VU University of Amsterdam:
Antibiotic treatment
Non perforated appendicitis
Children

Additional relevant MeSH terms:
Appendicitis
Acute Disease
Cecal Diseases
Digestive System Diseases
Disease Attributes
Gastroenteritis
Gastrointestinal Diseases
Infection
Intestinal Diseases
Intraabdominal Infections
Pathologic Processes
Anti-Bacterial Agents
Antibiotics, Antitubercular
Clavulanic Acid
Clavulanic Acids
Anti-Infective Agents
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014