{
  "abstract": "Objective To compare a non-operative treatment strategy with appendectomy for children with simple appendicitis, in terms of complications, avoidance of appendectomy, health related quality of life, and costs, after one year of follow-up.Design Non-inferiority randomised controlled trial.Setting 15 academic or general teaching hospitals, Netherlands, 1 January 2017 to 19 October 2023.Participants302 children, aged 7-17 years with imaging confirmed simple appendicitis, excluding those with a faecolith.Interventions Participants were randomised to the non-operative treatment strategy group (n=151) or the appendectomy group (n=151). The non-operative treatment strategy group received 48 hours of intravenous amoxicillin-clavulanic acid and gentamicin, followed by five days of oral amoxicillin-clavulanic acid.Main outcome measures The primary outcome was the proportion of participants with a complication within one year (non-inferiority margin of 5%). Secondary outcomes were the number of participants not requiring appendectomy, health related quality of life, and costs.Results In the intention-to-treat population, 14/151 (9.3%) participants in the non-operative treatment strategy group versus 13/151 (8.6%) in the appendectomy group had a complication during the one year follow-up period (absolute risk difference 0.7%, upper limit of 95% confidence interval (CI) 7.1%). Appendectomy was avoided in 105/151 (69.5%) participants in the non-operative treatment strategy group. No difference was found in health related quality of life between the treatment groups. Costs (both direct and societal) were lower in the non-operative treatment strategy group (mean difference €767 (£668; US$902), 95% CI 320 to 1214 for direct costs and €874, 118 to 1631 for societal costs). In the non-operative treatment strategy group, length of hospital stay was significantly longer (3.3±2.4  v 1.9±1.2 days, mean difference 1.5, 95% CI 1.1 to 1.9) and more unscheduled healthcare visits occurred. Patient satisfaction measured by the Net Promoter Score was significantly lower in the non-operative treatment strategy group (18.9±4.6% v 48.0±5.8%, mean difference −29.1, 95% CI−30.8 to −27.4) at the one year follow-up.Conclusions Non-inferiority of a non-operative treatment strategy for acute simple appendicitis in children could not be proven significantly. Most of the 95% CI was within the 5% non-inferiority margin, however, with a probability of 90.7% that a non-operative treatment strategy resulted in an increase in complications of ≤5%. Absolute risk difference in the proportion of participants with complications was marginal. Surgery was avoided in about 70% of participants in the non-operative treatment strategy group. Health related quality of life was comparable between the treatment strategies. A non-operative treatment strategy was associated with lower costs, but longer time in hospital, more unscheduled healthcare visits, and lower patient satisfaction at the one year follow-up, measured by the Net Promoter Score.Trial registration NCT02848820; NTR5977.",
  "authors": [
    {
      "affiliations": [
        "Department of Paediatric Surgery, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands",
        "Amsterdam Reproduction and Development Research Institute, Amsterdam, Netherlands",
        "University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, Netherlands"
      ],
      "name": "Paul van Amstel"
    },
    {
      "affiliations": [
        "Department of Paediatric Surgery, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands",
        "University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, Netherlands"
      ],
      "name": "Said Bachiri"
    },
    {
      "affiliations": [
        "Department of Paediatric Surgery, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands"
      ],
      "name": "Max Knaapen"
    },
    {
      "affiliations": [
        "Kennisinstituut van de Federatie Medisch Specialisten, Utrecht, Netherlands"
      ],
      "name": "Johanna H van der Lee"
    },
    {
      "affiliations": [
        "Centre for Reproductive Medicine, University of Amsterdam, Amsterdam UMC, Amsterdam, Netherlands"
      ],
      "name": "Rik van Eekelen"
    },
    {
      "affiliations": [
        "Department of Surgery, Amsterdam UMC-Locatie AMC, Amsterdam, Netherlands"
      ],
      "name": "Willem A Bemelman"
    },
    {
      "affiliations": [
        "Stichting Kind & Zorg, Utrecht, Netherlands"
      ],
      "name": "Hester Rippen-Wagner"
    },
    {
      "affiliations": [
        "Department of Surgery, Noordwest Ziekenhuisgroep, Alkmaar, Netherlands"
      ],
      "name": "Taco S Bijlsma"
    },
    {
      "affiliations": [
        "Department of Surgery, Rijnstate, Arnhem, Netherlands"
      ],
      "name": "Charlotte F J M Blanken-Peeters"
    },
    {
      "affiliations": [
        "Department of Surgery, Zuyderland, Heerlen/Sittard, Netherlands"
      ],
      "name": "Evert-Jan G Boerma"
    },
    {
      "affiliations": [
        "Department of Surgery, St Antonius Ziekenhuis, Nieuwegein, Netherlands"
      ],
      "name": "Anne Loes van den Boom"
    },
    {
      "affiliations": [
        "Department of Surgery, Maxima Medisch Centrum, Veldhoven, Netherlands"
      ],
      "name": "Frank J C van den Broek"
    },
    {
      "affiliations": [
        "Department of Surgery, Rode Kruis Ziekenhuis, Beverwijk, Netherlands"
      ],
      "name": "Huib A Cense"
    },
    {
      "affiliations": [
        "Department of Surgery, Gelre Hospital, Apeldoorn, Netherlands"
      ],
      "name": "Peter van Duijvendijk"
    },
    {
      "affiliations": [
        "Department of Surgery, Amstelland Hospital, Amstelveen, Netherlands"
      ],
      "name": "Frank P Garssen"
    },
    {
      "affiliations": [
        "Department of Surgery, Flevo Hospital, Almere, Netherlands"
      ],
      "name": "Klaas H in ’t Hof"
    },
    {
      "affiliations": [
        "Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands"
      ],
      "name": "Vanessa J Leijdekkers"
    },
    {
      "affiliations": [
        "Department of Surgery, Albert Schweitzer Ziekenhuis, Dordrecht, Netherlands"
      ],
      "name": "Maarten A Lijkwan"
    },
    {
      "affiliations": [
        "Department of Surgery, Juliana Children's Hospital, The Hague, Netherlands"
      ],
      "name": "Gerda W Zijp"
    },
    {
      "affiliations": [
        "Department of Paediatric Surgery, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands"
      ],
      "name": "Hugo A Heij"
    },
    {
      "affiliations": [
        "Department of Paediatric Surgery, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands",
        "Amsterdam Reproduction and Development Research Institute, Amsterdam, Netherlands",
        "University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, Netherlands"
      ],
      "name": "Joep P M Derikx"
    },
    {
      "affiliations": [
        "Department of Paediatric Surgery, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands",
        "Amsterdam Reproduction and Development Research Institute, Amsterdam, Netherlands",
        "University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, Netherlands"
      ],
      "name": "Ernest L W van Heurn"
    },
    {
      "affiliations": [
        "Department of Paediatric Surgery, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands",
        "Amsterdam Reproduction and Development Research Institute, Amsterdam, Netherlands",
        "University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, Netherlands"
      ],
      "name": "Roel Bakx"
    },
    {
      "affiliations": [
        "Department of Paediatric Surgery, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands",
        "Amsterdam Reproduction and Development Research Institute, Amsterdam, Netherlands",
        "University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, Netherlands"
      ],
      "name": "Ramon R Gorter"
    },
    {
      "affiliations": [],
      "name": "on behalf of the APAC collaborative study group"
    }
  ],
  "title": "Non-operative treatment strategy versus surgery for children with simple appendicitis: non-inferiority randomised controlled trial",
  "uid": "f19b3fad-be00-59d7-8200-6aa90450761f"
}