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Initial Non-operative Treatment Strategy Versus Appendectomy Treatment Strategy for Simple Appendicitis in Children (APAC)

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ClinicalTrials.gov Identifier: NCT02848820
Recruitment Status : Recruiting
First Posted : July 29, 2016
Last Update Posted : July 14, 2020
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
VU University Medical Center
Information provided by (Responsible Party):
Ramon Gorter, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:

OBJECTIVE

The aim of this study is to compare the effectiveness of initial non-operative treatment strategy (reserving appendectomy for those not responding or with recurrent disease) with immediate appendectomy in children from 7 to 17 years old, inclusive, with acute simple appendicitis in terms of complications, health-related QOL and costs.

Main research question: What is the difference in proportion of patients experiencing complications within 1 year between both strategies in children from 7 to 17 years old, inclusive, with acute simple appendicitis?


Condition or disease Intervention/treatment Phase
Appendicitis Drug: Augmentin + Gentamicin Procedure: Appendectomy Phase 4

Detailed Description:
Initial non-operative treatment of acute simple appendicitis has recently been investigated in both the adult as the paediatric population. In the adult population, six Randomised Controlled Trial (RCTs) showed that an appendectomy could be avoided in 40-76% of the patients at the end of their follow-up period. Despite the fact that some patients need to undergo a delayed appendectomy, it has been demonstrated in systematic reviews that non-operative treatment strategy is associated with a significant reduction in complications, faster recovery and return to work, less pain duration and analgesic medication consumption. In children only pilot data is yet available. Short-term success rates of this strategy (including of the investigators own pilot cohort study) are between the 83-92%. Long-term results (one-year follow-up) are available from two studies; 62-75% did not require an appendectomy. No large RCT have yet been conducted in the paediatric population. It is therefore essential to generate high quality empirical evidence regarding this strategy in this subset of patients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 334 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Initial Non-operative Treatment Strategy Versus Appendectomy Treatment Strategy for Simple Appendicitis in Children Aged 7-17 Years Old - Antibiotics Versus Primary Appendectomy in Children With Simple Appendicitis: APAC Study
Actual Study Start Date : December 2016
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Appendicitis

Arm Intervention/treatment
Experimental: Augmentin + Gentamicin

Initial non-operative treatment strategy reserving an appendectomy for those not responding or with recurrent disease. It consist of:

Clinical observation for 48 hours with administration of 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 for 48 hours. If after 48 hours the patient fulfils the predefined discharge criteria, 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 and discharge. An appendectomy is reserved for those patients with clinical deterioration, non-improvement after 72 hours or recurrent appendicitis.

Pain medication according to national protocol.

Drug: Augmentin + Gentamicin
Amoxicillin/clavulanic acid (Augmentin) 25/2.5mg 6-hourly (total 100/10 mg/kg daily; maximum 6000/600mg a day) intravenously for 48 hours Oral amoxicillin/clavulanic acid 50/12.5 mg/kg 8-hourly (max 1500/375mg a day) for in total 7 days Gentamicin 7mg/kg once daily for 48 hours
Other Name: Amoxicillin/clavulanic acid (Augmentin) + Gentamicin

Active Comparator: Operative treatment strategy
Clinical observation and semi-urgent appendectomy. Pre-, peri- and postoperative care according to local protocol. No routine postoperative antibiotics. Discharge if the patient fulfils the predefined discharge criteria. Pain medication according to national protocol.
Procedure: Appendectomy
Pre-, peri- and postoperative care according to local protocol. No routine postoperative antibiotics




Primary Outcome Measures :
  1. Proportion of patients experiencing complications [ Time Frame: One year follow up ]

Secondary Outcome Measures :
  1. Number of days absent from school, social or sport events [ Time Frame: 7 days, 1,6,12 months ]
  2. Number of days absent from work [ Time Frame: 7 days, 1,6,12 months ]
  3. Total number of extra visits (not the already scheduled ones) to the outpatient clinic, general practitioners office or emergency department for abdominal pain. [ Time Frame: 7 days, 1,6,12 months ]
  4. Total length of hospital stay during the follow-up period for strategy related treatment or complications [ Time Frame: 7 days, 1,6,12 months ]
  5. Total days of analgesics medication use. [ Time Frame: one month ]
  6. Pain score measured by the Visual Analogue Scale (VAS) [ Time Frame: Clinical phase (up to 7 days) ]
  7. Proportion of patients with missed diagnosis of complex appendicitis with risk of peritonitis [ Time Frame: 7 days, 1,6,12 months ]
  8. Proportion of patients not having to undergone appendectomy [ Time Frame: 7 days, 1,6,12 months ]
  9. Proportion of patients experiencing recurrent appendicitis [ Time Frame: 7 days, 1,6,12 months ]
  10. Proportion of patients experiencing early failure of initial non-operative treatment. [ Time Frame: 7 days, 1,6,12 months ]
  11. Proportion of patients that undergo interval appendectomy. [ Time Frame: 7 days, 1,6,12 months ]
  12. Quality of life questionnaire (CHQ-CF87, EQ-5d-Youth, EQ-5d-Proxy) [ Time Frame: 7 days, 1,6,12 months ]
  13. Medical and non-medical costs (Health and Labor questionnaire) [ Time Frame: 1,6,12 months ]
  14. Quality adjusted life years (QALY's). Calculating using outcome 13 and 14 [ Time Frame: 1,6,12 months ]
  15. Patient satisfaction questionnaire (PSQ-18 & Net promotor score) [ Time Frame: 7 days, 1,6,12 months ]
  16. Promoting and obstructing factors of implementability measured by questionnaires [ Time Frame: 12 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 7-17 years
  • Radiologically confirmed simple appendicitis, defined as:

    1. Clinical findings:

      • Unwell, but not generally ill
      • Localized tenderness in the right iliac fossa region
      • Normal/hyperactive bowel sounds
      • No guarding
      • No mass palpable
    2. Ultrasonography:

      • Incompressible appendix with an outer diameter of ≥6 mm
      • Hyperaemia within the appendiceal wall
      • Without faecolith
      • Infiltration of surrounding fat
      • No signs of perforation
      • No signs of intra-abdominal abscess/phlegmon

Exclusion Criteria:

  • Generalized peritonitis, complex appendicitis or sepsis (based upon predefined criteria and scoring system).
  • Scoring system: As scoring system was developed determining the risk of complex appendicitis based upon five pre-operative variable. Points have been awarded to each variable. In case the total score is less than 4 points, the patient is likely to have a simple appendicitis. In case the score is 4 or more points, the chance of having complex appendicitis is significant and those children will be excluded from this study. Variables:

    • Diffuse abdominal guarding (3 points)
    • C-Reactive Protein level more than 38 mg/L (2 points)
    • Signs on ultrasound indicative of complex appendicitis (2 points)
    • More than one day abdominal pain (2 points)
    • Temperature: more than 37.5 degree Celsius (1 point)
  • Faecolith (ultrasound)
  • Serious co-morbidity
  • Recurrent appendicitis
  • Suspicion of an underlying malignancy or inflammatory bowel disease
  • Documented type 1 allergy to the antibiotics used.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02848820


Contacts
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Contact: Ramon Gorter, MD 0031-205665693 rr.gorter@vumc.nl

Locations
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Netherlands
Medical Center Alkmaar Not yet recruiting
Alkmaar, Netherlands
Contact: Taco Bijlsma, MD PhD         
Principal Investigator: Taco Bijlsma, MD PhD         
Flevoziekenhuis Recruiting
Almere, Netherlands
Contact: Klaas in 't Hof, MD PhD         
Principal Investigator: Klaas in 't Hof, MD PhD         
AMC Recruiting
Amsterdam, Netherlands
Contact: Roel Bakx, MD PhD         
Principal Investigator: Roel Bakx, MD PhD         
VU University medical center Recruiting
Amsterdam, Netherlands
Contact: Roel Bakx, MD PhD    0031-204442424    r.bakx@amc.uva.nl   
Principal Investigator: Roel Bakx, MD PhD         
Gelre Hospital Not yet recruiting
Apeldoorn, Netherlands
Contact: Hugo Bolhuis         
Principal Investigator: Hugo Bolhuis, MD         
Red Cross Hospital Recruiting
Beverwijk, Netherlands
Contact: Huib Cense, MD PhD         
Principal Investigator: Huib Cense, MD PhD         
Maxima medical center Not yet recruiting
Eindhoven, Netherlands
Contact: M Benders, MD PhD         
Principal Investigator: M Benders, MD PhD         
Admiraal de Ruyter Hospital Not yet recruiting
Goes, Netherlands
Contact: J Jansen, MD PhD         
Principal Investigator: J Jansen, MD PhD         
Elkerliek hospital Not yet recruiting
Helmond, Netherlands
Contact: M Guijt, MD         
Principal Investigator: M Guijt, MD         
MUMC Not yet recruiting
Maastricht, Netherlands
Contact: Wim van Gemert, MD PhD         
Principal Investigator: Wim van Gemert, MD PhD         
Antonius Hospital Not yet recruiting
Nieuwegein, Netherlands
Contact: Peter Go, MD PhD         
Principal Investigator: Peter Go, MD PhD         
Radboud UMC Not yet recruiting
Nijmegen, Netherlands
Contact: Ivo de Blaauw, MD PhD         
Principal Investigator: Ivo de Blaauw, MD PhD         
Erasmus MC Not yet recruiting
Rotterdam, Netherlands
Contact: Rene Wijnen, MD PhD         
Principal Investigator: Rene Wijnen, MD PhD         
UMCU Not yet recruiting
Utrecht, Netherlands
Contact: Caroline Hulsker, MD PhD         
Principal Investigator: Caroline Hulsker, MD PhD         
Sponsors and Collaborators
Ramon Gorter
ZonMw: The Netherlands Organisation for Health Research and Development
VU University Medical Center
Investigators
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Study Chair: Ernst van Heurn, MD PhD Pediatric Surgical Center of Amsterdam (VUmc & AMC)
Study Director: Ramon Gorter, MD Pediatric Surgical Center of Amsterdam (VUmc & AMC)
Principal Investigator: Roel Bakx, MD PhD Pediatric Surgical Center of Amsterdam (VUmc & AMC)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ramon Gorter, drs., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02848820    
Other Study ID Numbers: APAC2016
First Posted: July 29, 2016    Key Record Dates
Last Update Posted: July 14, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Will follow
Keywords provided by Ramon Gorter, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Appendicitis
Appendectomy
Antibiotics
Additional relevant MeSH terms:
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Appendicitis
Intraabdominal Infections
Infection
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Cecal Diseases
Intestinal Diseases
Amoxicillin
Gentamicins
Amoxicillin-Potassium Clavulanate Combination
Clavulanic Acids
Clavulanic Acid
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
beta-Lactamase Inhibitors