Clinical trial NCT06917612: Preserving or Resecting the Normal Appendix in Patients Undergoing Laparoscopy Surgery for Suspected Appendicitis
Official title: Normal Diagnostic Laparoscopy Versus Negative Appendectomy in Patients With a Normal Appendix Undergoing Laparoscopic Surgery for Suspected Appendicitis: a Target Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Appendicitis
Abdominal Pain (AP)
Diagnostic Laparoscopy
Laparoscopic Appendectomy
Neoplasms
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: Danish Institute for Public Health
First posted: 2025-04-08
Enrollment: 20000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients of all ages undergoing laparoscopic surgery for suspected appendicitis, as recorded in the nationwide Danish National Patient Register, are identified via diagnostic and surgical codes. Information on negative appendectomies is retrieved from the nationwide register of the Danish Pathology Data Bank.

We will use inverse probability weighting to adjust for and minimise bias derived from an imbalance in baseline covariates (sex, age, year of surgery, and hospital).

Brief summary: When appendicitis is suspected, patients are typically planned for emergency surgery preferably using a laparoscopic approach. Up to 20% of these patients will have a normal appendix, thus not suffering from appendicitis. Surgeons can either perform a normal diagnostic laparoscopy (leave the appendix in situ) or perform a negative appendectomy (resect the normal appendix). International guidelines recommend negative appendectomy based on weak evidence due to the risk of appendix cancer, but some countries and researchers advocate against negative appendectomy as these patients may experience more harm than if the appendix is left in situ. There are limited national guidelines and the decision is often left to the operating surgeon. Surgeons performing negative appendectomies argue that these prevent microappendicitis and the risk of a subsequent episode of appendicitis. As appendix cancers are rare, and a randomised controlled trial including this subgroup of patients with normal appendices undergoing emergency surgery for suspected appendicitis is unfeasible, an emulated target trial is planned.

This target trial aims to evaluate the effect of a normal diagnostic laparoscopy versus negative appendectomy during laparoscopic surgery for suspected appendicitis regarding cancer in the appendix and other complications such as death, reoperation, and readmission.

Detailed description: The target trial emmulates an unfeasible randomised controlled trial by using observational data to investigate the two treatment strategies (two groups) normal diagnostic laparoscopy versus negative appendectomy when a normal appendix is seen during surgery for suspected appendicitis. The assignment to the treatment strategies during surgery for suspected appendicitis is treated as randomised within the levels of the following baseline covariates; sex, age, year of index surgery, and hospital through inverse probability weighting. We will analyse data according to treatment assignment at baseline (intention-to-treat). Because the treatment strategies in this target trial are surgical, all participants will adhere to the surgical treatment strategy: neither a normal diagnostic laparoscopy nor a negative appendectomy at index surgery can be reversed. However, both may be followed by a reoperation, e.g., a new normal diagnostic laparoscopy or a laparoscopic appendectomy (for suspected appendicitis or stump appendicitis). However, this will not influence analyses but be recorded as an outcome.

As inverse probability weighting has been applied, no further adjustment in the pre-specified analyses below is needed.

The continuous outcome, delay of cancer diagnosis for the normal diagnostic laparoscopy group, will be descriptively reported as mean (SD) or median (IQR).

For dichotomous outcomes, the following analyses are planned:

* Kaplan-Meier curves for each group
* Incidence proportion (risk) including 95% CI for each group
* Relative risk
* Risk difference
* Number needed to treat
* Number needed to harm
* Test chi-square

Eligibility criteria: Inclusion Criteria:

* All ages and sexes
* Undergoing laparoscopic surgery for suspected appendicitis from 2005 to 2021
* Resected appendix without inflammation e.g., without appendicitis

Exclusion Criteria:

* Previous resection of the appendix (e.g., previous appendectomy, or resection of the gut including the appendix before January 1, 2005) based on data from surgical codes in the Danish National Patient Register
* Unable to be tracked in the Danish registers, such as a replacement personal identification number, or for those not residing in Denmark based on data from the Civil Registration System
* Diagnostic codes indicating appendix cancer at index surgery (C181), thus, not operated for suspected appendicitis
* Laparoscopic appendectomy converted to open surgery or other surgical procedures conducted contaminated with laparoscopic appendectomy, indicated a need for other surgical interventions because of disease

Primary outcomes:
measure: Cancer in the appendix
timeFrame: 2 years
measure: Appendix cancer
timeFrame: 2 years
Secondary outcomes:
measure: Delay in diagnosis of cancer
timeFrame: 2 years
measure: Death
timeFrame: 2 years
measure: Any reoperation
timeFrame: 1 year
measure: Abdominal reoperation
timeFrame: 1 year
measure: Resected appendix
timeFrame: 2 years
measure: Readmission
timeFrame: 1 year
Other outcomes:
measure: Subgroup analysis for outcomes at 1 year follow-up
timeFrame: 1 year
measure: Subgroup analysis for outcomes at 2 years follow-up
timeFrame: 2 year
measure: Subgroup analysis for outcomes at 5 years follow-up
timeFrame: 5 year
measure: Sensitivity analysis on comorbidity
timeFrame: 1 year
measure: Sensitivity analysis on umeasured confounding
timeFrame: 2 years
Locations:
Study officials:
affiliation: Herlev Hospital
name: Siv Fonnes, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: