Acute AppendicitisNCT06917612
Preserving or Resecting the Normal Appendix in Patients Undergoing Laparoscopy Surgery for Suspected Appendicitis
An observational study of Acute Appendicitis and Abdominal Pain (AP), run by Herlev Hospital.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Appendicitis, Abdominal Pain (AP), Diagnostic Laparoscopy
- What is being tested?
- Normal diagnostic laparoscopy and Negative appendectomy
- Type of treatment
- Surgery or procedure
- How many people
- 20,000 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2005to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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).
Who may be able to join
- All ages and sexes
- Undergoing laparoscopic surgery for suspected appendicitis from 2005 to 2021
- Resected appendix without inflammation e.g., without appendicitis
Who cannot join
- 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
About this study
Official title: Normal Diagnostic Laparoscopy Versus Negative Appendectomy in Patients With a Normal Appendix Undergoing Laparoscopic Surgery for Suspected Appendicitis: a Target Trial
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.
Read the 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
- Conditions
- Acute Appendicitis, Abdominal Pain (AP), Diagnostic Laparoscopy, Laparoscopic Appendectomy, Neoplasms
- Being tested
- Normal diagnostic laparoscopy, Negative appendectomy
- Medical subject headings
- Appendicitis, Abdominal Pain, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normal diagnostic laparoscopyProcedure or surgery
The appendix is left in situ e.g., not resected and no other surgical resection is needed to treat other diseases
Negative appendectomyProcedure or surgery
The appendix is resected but is without histopathological-confirmed inflammation and no other surgical resection is needed to treat other diseases
| Study group | Role | What they receive |
|---|---|---|
| Normal diagnostic laparoscopy group | The appendix is left in situ, e.g. not resected and no other surgical procedure is needed to treat other diseases, identified through both the nationwide Danish National Patient Register and Danish Pathology Data Bank Receives: Procedure: Normal diagnostic laparoscopy | |
| Negative appendectomy group | The appendix is resected but is without histopathological inflammation and no other surgical resection is needed to treat other diseases, identified through both the nationwide Danish National Patient Register and Danish Pathology Data Bank Receives: Procedure: Negative appendectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cancer in the appendix
Histopathologically verified cancer in the appendix (primary or metastasis) in the nationwide register the Danish Pathology Data Bank e.g., SNOMED morphology codes for cancer (M8** or M9**) in relation to the topography code of the appendix (T66000)
Measured: 2 years
Appendix cancer
Histopathologically verified appendix cancer (primary) in the nationwide register the Danish Pathology Data Bank e.g., SNOMED morphology codes for cancer (M8** or M9**) in relation to the topography code of the appendix (T66000)
Measured: 2 years
Secondary outcomes (6)
Delay in diagnosis of cancer
Time from index normal diagnostic laparoscopy to histopathologically verified cancer in the appendix in the nationwide register Danish Pathology Data Bank, e.g., SNOMED morphology codes for cancer (M8** or M9**) in relation to the topography code of the appendix (T66000)
Measured: 2 years
Death
All-cause death registered in the nationwide The Civil Registration System
Measured: 2 years
Any reoperation
Any reoperations registered in the nationwide Danish National Patient Register
Measured: 1 year
Abdominal reoperation
Abdominal reoperations registered in the nationwide Danish National Patient Register e.g., with surgical codes KJ* (gastrointestinal tract), KK* (urological), or KL***(gynecological)
Measured: 1 year
Resected appendix
Histopathological record of an appendix in the nationwide register the Danish Pathology Data Bank e.g., record with topography code of the appendix (T66000) after index surgery, including subdivision of morphology codes into appendicitis, negative appendectomy, appendix cancer, and other
Measured: 2 years
Readmission
Any readmissions registered in the nationwide Danish National Patient Register, including subdivisions into diagnostic codes relating to different diseases
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2025
- Study start1 Jan 2005
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute AppendicitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Institute for Public Health
- Responsible party
- Principal investigator, Siv Fonnes, Herlev Hospital
- Investigators
- Siv Fonnes, MD, PhD, Principal investigator, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06917612
- Sponsor's protocol ID
- HEH-SF-03
- Status last verified
- Apr 2025
- First submitted
- 1 Apr 2025
- Last updated
- 8 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The researchers have access to pseudonymised data provided by Statistics Denmark, and according to their rules and guidelines on transfer and data security (https://www.dst.dk/en/TilSalg/data-til-forskning/regler-og-datasikkerhed/regler-for-hjemtagelse-af-analyseresultater) information on individual level cannot be transferred outside Statistics Denmark's researcher machines.
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Normal Diagnostic Laparoscopy Versus Negative Appendectomy in Patients With a Normal Appendix Undergoing Laparoscopic Surgery for Suspected Appendicitis: a Target Trial
- ClinicalTrials.gov ID
- NCT06917612
- Acronym / sponsor ID
- HEH-SF-03
- Conditions
- Acute Appendicitis, Abdominal Pain (AP), Diagnostic Laparoscopy, Laparoscopic Appendectomy, Neoplasms
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20,000 participants (actual)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Collaborators
- Danish Institute for Public Health
- Study start
- 1 Jan 2005 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 8 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal diagnostic laparoscopy group | – | Procedure: Normal diagnostic laparoscopyThe appendix is left in situ, e.g. not resected and no other surgical procedure is needed to treat other diseases, identified through both the nationwide Danish National Patient Register and Danish Pathology Data Bank |
| Negative appendectomy group | – | Procedure: Negative appendectomyThe appendix is resected but is without histopathological inflammation and no other surgical resection is needed to treat other diseases, identified through both the nationwide Danish National Patient Register and Danish Pathology Data Bank |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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).
Key inclusion criteria (3 listed)
- All ages and sexes
- Undergoing laparoscopic surgery for suspected appendicitis from 2005 to 2021
- Resected appendix without inflammation e.g., without appendicitis
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Normal diagnostic laparoscopyThe appendix is left in situ e.g., not resected and no other surgical resection is needed to treat other diseases | Procedure or surgery | Normal diagnostic laparoscopy group |
| Negative appendectomyThe appendix is resected but is without histopathological-confirmed inflammation and no other surgical resection is needed to treat other diseases | Procedure or surgery | Negative appendectomy group |
Primary outcome
Cancer in the appendix
Time frame: 2 years
Histopathologically verified cancer in the appendix (primary or metastasis) in the nationwide register the Danish Pathology Data Bank e.g., SNOMED morphology codes for cancer (M8** or M9**) in relation to the topography code of the appendix (T66000)
Appendix cancer
Time frame: 2 years
Histopathologically verified appendix cancer (primary) in the nationwide register the Danish Pathology Data Bank e.g., SNOMED morphology codes for cancer (M8** or M9**) in relation to the topography code of the appendix (T66000)
6 secondary outcomes
Delay in diagnosis of cancer
Time frame: 2 years
Death
Time frame: 2 years
Any reoperation
Time frame: 1 year
Abdominal reoperation
Time frame: 1 year
Resected appendix
Time frame: 2 years
Readmission
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2025.
- Individual participant dataSharing planned: No. The researchers have access to pseudonymised data provided by Statistics Denmark, and according to their rules and guidelines on transfer and data security (https://www.dst.dk/en/TilSalg/data-til-forskning/regler-og-datasikkerhed/regler-for-hjemtagelse-af-analyseresultater) information on individual level cannot be transferred outside Statistics Denmark's researcher machines.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Siv Fonnes, MD, PhD principal investigator
Herlev Hospital
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Appendicitis and Abdominal Pain (AP), run by Herlev Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cancer in the appendix (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2025.