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Identification of the Optimal Treatment Strategy for Complex Appendicitis in the Pediatric Population (CAPP)

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ClinicalTrials.gov Identifier: NCT04755179
Recruitment Status : Recruiting
First Posted : February 16, 2021
Last Update Posted : February 16, 2021
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:

Aim of this study is to evaluate the effect of different treatment strategies on overall complications, health related-Quality of Life (hr-QOL) and costs among two subtypes of complex appendicitis in children (<18 years old).

Main research questions: What is the difference in overall complications at three months between:

Subgroup 1 (complex appendicitis without abscess/mass formation): Laparoscopic (LA) and open appendectomy (OA) Subgroup 2: (complex appendicitis with abscess/mass formation): Non-operative treatment (NOT) and direct appendectomy


Condition or disease Intervention/treatment
Appendicitis Appendix Mass Appendicitis Perforated Procedure: Laparoscopic appendectomy Procedure: Open appendectomy Procedure: Non-operative treatment Procedure: Direct appendectomy

Detailed Description:

Up till now initiated research projects worldwide mainly focus on simple appendicitis (questioning the necessity of an appendectomy). However, complex appendicitis is associated with significant morbidity (up to 30%), prolonged hospital stay and high costs. Identification of the optimal treatment strategy for children with complex appendicitis is therefore essential. Heterogeneity in the treatment of complex appendicitis still exists in daily practice and reflects the lack of high-quality data and emphasizes the need for well-designed studies. Complex appendicitis can be divided into two subtypes:

  1. Complex appendicitis without mass/abscess. (subgroup 1) Although (inter)national guidelines agree that appendectomy should be usual care, the optimal approach (open or laparoscopy) is unclear. Laparoscopic appendectomy (LA) is increasingly applied both in adults (80%) and children (60%). Benefits reported for LA in children are, but not limited to, less superficial site infection (SSI), reduced length of hospital stay and significant less postoperative bowel obstruction compared with open appendectomy (OA). Reluctance for usage of LA in this specific subgroup, however, remains due to the potential higher incidence of post-appendectomy abscess formation (PAA) reported. However, the quality of studies on this topic is low and there is considerable inconsistency in results.
  2. Complex appendicitis with mass/abscess. (subgroup 2) The recommendation made in our national guideline (to perform direct appendectomy in this subgroup) is not in line with the available literature. A recent Cochrane review on this topic could only include two trials and stated that no firm conclusions could be drawn. An older systematic review, including 7 studies in children, concluded that non-operative treatment (NOT) led to fewer complications, specifically SSI and PAA, when compared to direct appendectomy. Still the recommendation from our national guideline is to perform a direct appendectomy based upon good experiences in the pediatric academic centers.

In order to investigate the optimal treatment for children with complex appendicitis we will perform a nationwide, multi-center, comparative, prospective cohort study. For the purpose of this study, treatment strategies will be standardized among the participating hospitals in order to reduce heterogeneity. Prospectively derived, high quality data will be sufficient to answer the research questions regarding the optimal treatment strategy for each subtype of complex appendicitis in the pediatric population. As it is a non-randomized prospective cohort study, propensity score matching technique will be performed in order to estimate the effect of the treatments adjusted for potential confounders.

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Study Type : Observational
Estimated Enrollment : 1308 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Identification of the Optimal Treatment Strategy for Complex Appendicitis in the Pediatric Population
Actual Study Start Date : August 12, 2019
Estimated Primary Completion Date : August 12, 2022
Estimated Study Completion Date : August 12, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Abscess Appendicitis

Group/Cohort Intervention/treatment
Complex appendicitis without abscess or mass formation
All children (<18 years old) that present with a suspicion of complex appendicitis without clinical or radiological signs of abscess or mass formation. Preoperative suspicion of complex appendicitis is based upon a previously developed clinical scoring system.
Procedure: Laparoscopic appendectomy

Laparoscopic appendectomy is performed according to daily practice but with the following standardized key points:

  1. Conventional laparoscopy (three-trocar technique)
  2. In case of purulent fluid: Suction and no peritoneal lavage procedure
  3. Skelletizing of the mesoappendix (coagulation/clips according to routine practice locally)
  4. Appendiceal stump closure: with two endoloops and dissected between the endoloops. In case of involvement of the appendiceal base, the use of endostapler is recommended.
  5. Withdrawal of appendix: principle of abdominal wall protection is followed (trocar technique / endobag)
  6. No drain placement, no nasogastric tube, and no urinary catheter routinely, only on indication.
  7. Closure of wounds as appropriate

Procedure: Open appendectomy

Open appendectomy will be performed according to the following standardized key points:

  1. Gridiron incision at the right lower quadrant. (McBurney's point)
  2. After obtaining access to the abdominal cavity the principle of abdominal wall protection will be followed.
  3. The appendiceal stump will be closed by ligation, not a purse string suture.
  4. Closure of wounds as appropriate

Complex appendicitis with abscess or mass formation
All children (<18 years old) that present with a suspicion of complex appendicitis with clinical or radiological signs of abscess or mass formation. Preoperative suspicion of complex appendicitis is based upon a previously developed clinical scoring system.
Procedure: Non-operative treatment

Non-operative treatment consisting of administration of intravenous antibiotics with or without drainage procedures (in case of an abscess), reserving an appendectomy for those not responding or with recurrent disease.

One of the two antibiotic regiments:

  1. Combination A:

    1. Amoxicillin/clavulanic acid 25/2.5mg/kg 6 hourly (total 100/10 mg/kg daily. Maximum 6000/600mg a day) for children <40 kg OR Amoxicillin/clavulanic acid 1000/200mg/kg 8 hourly (total 3000/6000 mg/kg daily) for children > 40 kg
    2. Gentamicin 7mg/kg once daily
  2. Combination B:

    1. Cefuroxim 25 mg/kg 6 hourly (total 100 mg/kg/day. Maximum 6gram/day)
    2. Metronidazole 10mg/kg 8hourly (total 30 mg/kg/day. Maximum 4000 mg/day) In case of peri-appendicular abscess the decision can be made to perform a drainage procedure either percutaneously or surgical.

Procedure: Direct appendectomy
laparoscopic or open appendectomy as described




Primary Outcome Measures :
  1. Overall complications [ Time Frame: 3 months ]
    The proportion of patients experiencing any complication within 3 months after inclusion


Secondary Outcome Measures :
  1. Postappendectomy abscess [ Time Frame: 3 months ]
    Proportion patients with a postappendectomy abscess

  2. Superficial Site Infection [ Time Frame: 3 months ]
    Proportion of patients with a superficial site infection

  3. Secondary bowel obstruction [ Time Frame: 3 months ]
    Proportion of patients with a secondary/prolonged bowel obstruction

  4. Days absent from school, social or sports events [ Time Frame: 30 days, 3 months ]
    Number of days absent from school, social or sports events

  5. Number of days absent from work [ Time Frame: 30 days, 3 months ]
    Number of days that parents are absent from work

  6. Total number of extra visits [ Time Frame: 30 days, 3 months ]
    Total number of extra visits to the outpatient clinic, general pratctitioner's office or emergency department

  7. Length of hospital stay [ Time Frame: 3 months ]
    Total length of hospital stay during follow-up due to trategy related treatment or complications

  8. Level of pain [ Time Frame: at inclusion/baseline (=day 0), 3 days, 5 days, 30 days, 3 months ]
    Level of pain measured according to the Visual Analogue Scale (0-10 points, higher scores indicating worse outcomes)

  9. Pain medication utilization [ Time Frame: 30 days, 3 months ]
    Pain medication utilization during admission

  10. Need for appendectomy [ Time Frame: 3 months ]
    Proportion of patients not having to undergo appendectomy within 3 months after start of non-operative treatment

  11. Recurrent appendicitis [ Time Frame: 3 months ]
    Proportion of patients experiencing recurrent appendicitis within 3 months after inclusion

  12. Early failure of non-operative treatment [ Time Frame: 3 months ]
    Proportion of patients experiencing early failure of initial non-operative treatment

  13. Quality of Life questionnaire (EQ-5d-Youth/EQ-5d-Proxy) [ Time Frame: at inclusion/baseline (=day 0), 30 days, 3 months ]
    QoL measured by the validated EQ-5d-Youth / EQ-5d-Proxy questionnaire (0-1 point, higher scores indicating better outcome)

  14. Quality of Life questionnaire (PedsQL 4.0) [ Time Frame: at inclusion/baseline (=day 0), 30 days, 3 months ]
    QoL measured by the validated Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) (0-100 points, higher scores indicating better outcome) Labor Questionnaire (HLQ), Medical Consumption Questionnaire (iMCQ) and Productivity Consumption Questionnaire (iPCQ) and gathered actual health care cost

  15. Medical costs (iMCQ) [ Time Frame: at inclusion/baseline (=day 0), 30 days, 3 months ]
    Medical costs measured by the iMedical Consumption Questionnaire

  16. Non-medical / indirect costs (iPCQ) [ Time Frame: at inclusion/baseline (=day 0), 30 days, 3 months ]
    Non-medical / indirect costs measured by the iProductivity Cost Questionnaire

  17. Quality adjusted life months (QALM's) [ Time Frame: 3 months ]
    Quality adjusted life months calculated using outcomes 14 -17

  18. Patient satisfaction questionnaire (PSQ-18) [ Time Frame: 3 months ]
    Patient satisfaction measured by the Patient Satisfaction Questionnaire (PSQ) (0-100, higher scores indicating better outcome)

  19. Patient satisfaction questionnaire (Net promotor score) [ Time Frame: 3 months ]
    Patient satisfaction measured by the NET PROMOTOR SCORE (0-10, higher scores indicating better outcome)



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
All children that present with a preoperative suspicion of complex appendicitis. This suspicion is based on 4 points or more on the abovementioned complex appendicitis scoring system OR a high index of suspicion of complex appendicitis by the treating physician.
Criteria

Inclusion Criteria:

Eligible for inclusion are all children <18 years old that need to undergo treatment for the suspicion of complex appendicitis. Suspicion of complex appendicitis is based upon the following predefined criteria:

4 or more points on our scoring system developed to predict complex appendicitis. The diagnostic accuracy of this scoring system is 91% (Range: 84-98%). This scoring system consists of five variables (clinical, biochemical and radiological,each awarded points). In case the total score is 4 or more points, the patient is likely to have complex appendicitis. Variables included in the scoring system are:

  • Diffuse abdominal guarding (3 points)
  • CRP level more than 38 mg/L (2 points)
  • Signs on ultrasound / imaging indicative for complex appendicitis (2 points)
  • More than one day abdominal pain (2 points)
  • Temperature more than 37.5 degrees Celsius (1 point)

Or

High index of suspicion of complex appendicitis by the treating physician. If this is the case, the treating physician will make pre-treatment note upon what clinical, biochemical or radiological variable the high index of suspicion is based.

Exclusion Criteria:

  • Adult patients (=18 years old)
  • Children with a suspicion of simple appendicitis (based upon the previous mentioned scoring system and radiological features)

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): NCT04755179


Contacts
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Contact: Ramon Gorter, MD PhD 0031-205665693 rr.gorter@amsterdamumc.nl
Contact: Paul van Amstel, MD 0031-205665693 p.vanamstel@amsterdamumc.nl

Locations
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Sponsors and Collaborators
Ramon Gorter
ZonMw: The Netherlands Organisation for Health Research and Development
VU University Medical Center
Investigators
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Principal Investigator: Ramon Gorter, MD PhD Amsterdam UMC
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Responsible Party: Ramon Gorter, Dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT04755179    
Other Study ID Numbers: W18_302#18.348
First Posted: February 16, 2021    Key Record Dates
Last Update Posted: February 16, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ramon Gorter, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Complex appendicitis
Children
Treatment
Additional relevant MeSH terms:
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Appendicitis
Intraabdominal Infections
Infection
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Cecal Diseases
Intestinal Diseases