Acute AppendicitisNCT04806789
Plasma Sodium: a Predictor of Perforation in Acute Appendicitis. (The NAP-study)
An observational study of Acute Appendicitis and Children, Only, run by Urban Fläring at 1 site in Sweden.
Trial summary
This clinical prospective diagnostic accuracy study assesses plasma sodium concentration using blood gas analysis at the emergency department in children, age 1-15 years, with suspected acute appendicitis. Read more about this study
- Who is it for?
- Ages 1 year to 15 years
- Conditions the study is for
- Acute Appendicitis, Children, Only
- How many people
- 451 participants
- Where
- 1 siteSweden
- Study dates
- 1 Jun 2021to 25 Nov 2024
- 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 1 year to 15 years
- All sexes
- No healthy volunteers
- Child
Study population: Children with suspected acute appendicitis
Who may be able to join
- Children with suspected acute appendicitis
Who cannot join
- Chronic metabolic disease
- Endocrinological disease
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Pediatric Perioperative Medicine and Intensive Care
Stockholm, 17176
About this study
This clinical prospective diagnostic accuracy study assesses plasma sodium concentration using blood gas analysis at the emergency department in children, age 1-15 years, with suspected acute appendicitis. The overall assumption is that using plasma sodium as a biomarker, a cut-off value of <136 mmol/L will differentiate perforated from non-perforated acute appendicitis. In addition, traditionally used clinical diagnostic variables as well as radiology used in the diagnosis of acute appendicitis will also be obtained. Histopathology will be used to define if the appendix is perforated or not.
Read the detailed description
Background: The historical dogma that acute appendicitis always progresses to gangrene and perforation has been rejected. In addition, there is evolving evidence that medical treatment of non-perforated acute appendicitis is safe. On the other hand, perforated acute appendicitis requires appendectomy [Andersson]. Therefore, it is important to differentiate perforation from non-perforation in order to enable proper treatment.
In a pilot-study in children with acute appendicitis (n=80), plasma sodium was shown to be an independent predictor differentiating between perforated and non-perforated acute appendicitis [Lindestam]. Using plasma sodium at a cut-off value of <136 mmol/L, the odds ratio of having a perforated acute appendicitis was 31.9 (95% CI, 6.3- 161.9) with an area under the receiver operating curve of 0.93. Sensitivity and specificity were 0.87 (95 % CI 0.60-0.98) and 0.83 (95 % CI 0.72-0.91). Similar results have later been shown by another research group [Pogorelic]. Possible mechanism for lower plasma sodium among patients with perforation is higher concentration of arginin-vasopressin, which has previously been shown [Lindestam].
Methods: Participants (n=450 in total) whereof 150 in Sweden, 150 in Republic of South Africa, 50 in Germany, 50 in Denmark and 50 in Norway will be included in the study. The patients/parents will be asked for participation in the study and included after decision of surgery has been made by the attendant surgeon. At this timepoint, (i) variables from clinical examination/history (presence of right iliac fossa pain, rebound tenderness, duration of symptoms, vomiting, temperature, gender, age, weight, (ii) blood sampling: blood gas (including plasma sodium), C-reactive protein, neutrophiles, White blood cell count (obtained at the emergency department) and (iii) radiology has been obtained. No intervention is planned. These variables will also be used to calculate the Appendicitis Inflammatory Responce (AIR) score [Scott]. Thereafter, plasma sodium concentration will be added and the score will be recalculated.
After surgery, histopathology will be used to determine if the appendix is perforated or not.
- Conditions
- Acute Appendicitis, Children, Only
- Keywords
- Acute appendicitis, Children, Plasma Sodium
- Medical subject headings
- Appendicitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Children with suspected acute appendicitis | Cohort: Children with suspected acute appendicitis. Clinical examination (including history of nausea, vomiting, temperature, information of rebound tenderness, right iliac fossa pain, duration of symptoms, gender and weight) and blood samples will be obtained at the emergency department (blood gas, C-reactive protein, neutrophiles and white blood cell count). Radiology (ultrasound and/or computed tomography) will be performed thereafter. Outcome measures Primary outcome measure: Plasma sodium. To investigate if plasma sodium is an independent predictor of perforation in children with acute appendicitis. In advance, five variables (Plasma sodium, C-reactive protein, symptom duration, age and temperature) will be included in the final multivariable analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma sodium concentration as a predictor for perforated acute appendicitis.
Plasma sodium will be dichotomized at 136 mmol/L. Lower concentration are hypothesized to indicate perforated acute appendicitis.
Measured: Possible predictive variables will only be obtained at one occation on the day of admission to the emergency department.
Secondary outcomes (1)
Plasma sodium concentration adding precision to the diagnostic performance of "the Appendicitis Inflammatory Response (AIR) score".
This score uses anthropometric and laboratory values that will be obtained on admission to the emergency department. Adding plasma sodium to these values in regression analysis to increase possibility to predict perforated acute appendicitis.
Measured: Diagnostic values of interest are only obtained at one occasion on admission to the emergency department
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start1 Jun 2021
- Primary completion25 Nov 2024
- Study completion25 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- 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
- 451 participants (actual)
Sponsor and investigators
- Lead sponsor
- Urban Fläring
- Sponsor type
- University, hospital or other
- Collaborators
- Odense University Hospital, Charite University, Berlin, Germany, Red Cross War Memorial Childrens Hospital, Oslo University Hospital
- Responsible party
- Sponsor-investigator, Urban Fläring, Karolinska Institutet
- Investigators
- Urban Fläring, Ass Prof, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04806789
- Sponsor's protocol ID
- K 2021-2319
- Status last verified
- Nov 2024
- First submitted
- 12 Mar 2021
- Last updated
- 27 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is likely that we will share data on request when the study is published,
Publications
Andersson RE, Petzold MG. Nonsurgical treatment of appendiceal abscess or phlegmon: a systematic review and meta-analysis. Ann Surg. 2007 Nov;246(5):741-8. doi: 10.1097/SLA.0b013e31811f3f9f.
PubMed 17968164Lindestam U, Almstrom M, Jacks J, Malmquist P, Lonnqvist PA, Jensen BL, Carlstrom M, Krmar RT, Svensson JF, Norberg A, Flaring U. Low Plasma Sodium Concentration Predicts Perforated Acute Appendicitis in Children: A Prospective Diagnostic Accuracy Study. Eur J Pediatr Surg. 2020 Aug;30(4):350-356. doi: 10.1055/s-0039-1687870. Epub 2019 Apr 25.
PubMed 31022754Pogorelic Z, Luksic B, Nincevic S, Luksic B, Polasek O. Hyponatremia as a predictor of perforated acute appendicitis in pediatric population: A prospective study. J Pediatr Surg. 2021 Oct;56(10):1816-1821. doi: 10.1016/j.jpedsurg.2020.09.066. Epub 2020 Oct 8.
PubMed 33153722Scott AJ, Mason SE, Arunakirinathan M, Reissis Y, Kinross JM, Smith JJ. Risk stratification by the Appendicitis Inflammatory Response score to guide decision-making in patients with suspected appendicitis. Br J Surg. 2015 Apr;102(5):563-72. doi: 10.1002/bjs.9773. Epub 2015 Mar 2.
PubMed 25727811
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma Sodium: a Predictor of Perforation in Acute Appendicitis. (The NAP-study)
- ClinicalTrials.gov ID
- NCT04806789
- Acronym / sponsor ID
- K 2021-2319
- Conditions
- Acute Appendicitis, Children, Only
- Keywords
- Acute appendicitis, Children, Plasma Sodium
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 451 participants (actual)
- Lead sponsor
- Urban FläringUniversity, hospital or other
- Collaborators
- Odense University Hospital, Charite University, Berlin, Germany, Red Cross War Memorial Childrens Hospital, Oslo University Hospital
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 25 Nov 2024 (actual)
- Study completion
- 25 Nov 2024 (actual)
- First posted
- 19 Mar 2021 (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.
This clinical prospective diagnostic accuracy study assesses plasma sodium concentration using blood gas analysis at the emergency department in children, age 1-15 years, with suspected acute appendicitis. The overall assumption is that using plasma sodium as a biomarker, a cut-off value of <136 mmol/L will differentiate perforated from non-perforated acute appendicitis. In addition, traditionally used clinical diagnostic variables as well as radiology used in the diagnosis of acute appendicitis will also be obtained. Histopathology will be used to define if the appendix is perforated or not.
Detailed description
Background: The historical dogma that acute appendicitis always progresses to gangrene and perforation has been rejected. In addition, there is evolving evidence that medical treatment of non-perforated acute appendicitis is safe. On the other hand, perforated acute appendicitis requires appendectomy [Andersson]. Therefore, it is important to differentiate perforation from non-perforation in order to enable proper treatment.
In a pilot-study in children with acute appendicitis (n=80), plasma sodium was shown to be an independent predictor differentiating between perforated and non-perforated acute appendicitis [Lindestam]. Using plasma sodium at a cut-off value of <136 mmol/L, the odds ratio of having a perforated acute appendicitis was 31.9 (95% CI, 6.3- 161.9) with an area under the receiver operating curve of 0.93. Sensitivity and specificity were 0.87 (95 % CI 0.60-0.98) and 0.83 (95 % CI 0.72-0.91). Similar results have later been shown by another research group [Pogorelic]. Possible mechanism for lower plasma sodium among patients with perforation is higher concentration of arginin-vasopressin, which has previously been shown [Lindestam].
Methods: Participants (n=450 in total) whereof 150 in Sweden, 150 in Republic of South Africa, 50 in Germany, 50 in Denmark and 50 in Norway will be included in the study. The patients/parents will be asked for participation in the study and included after decision of surgery has been made by the attendant surgeon. At this timepoint, (i) variables from clinical examination/history (presence of right iliac fossa pain, rebound tenderness, duration of symptoms, vomiting, temperature, gender, age, weight, (ii) blood sampling: blood gas (including plasma sodium), C-reactive protein, neutrophiles, White blood cell count (obtained at the emergency department) and (iii) radiology has been obtained. No intervention is planned. These variables will also be used to calculate the Appendicitis Inflammatory Responce (AIR) score [Scott]. Thereafter, plasma sodium concentration will be added and the score will be recalculated.
After surgery, histopathology will be used to determine if the appendix is perforated or not.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children with suspected acute appendicitis | – | –Cohort: Children with suspected acute appendicitis. Clinical examination (including history of nausea, vomiting, temperature, information of rebound tenderness, right iliac fossa pain, duration of symptoms, gender and weight) and blood samples will be obtained at the emergency department (blood gas, C-reactive protein, neutrophiles and white blood cell count). Radiology (ultrasound and/or computed tomography) will be performed thereafter. Outcome measures Primary outcome measure: Plasma sodium. To investigate if plasma sodium is an independent predictor of perforation in children with acute appendicitis. In advance, five variables (Plasma sodium, C-reactive protein, symptom duration, age and temperature) will be included in the final multivariable analysis |
Who may qualify
- Ages
- 1 year to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Children with suspected acute appendicitis
Key inclusion criteria (1 listed)
- Children with suspected acute appendicitis
Key exclusion criteria (2 listed)
- Chronic metabolic disease
- Endocrinological disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Plasma sodium concentration as a predictor for perforated acute appendicitis.
Time frame: Possible predictive variables will only be obtained at one occation on the day of admission to the emergency department.
Plasma sodium will be dichotomized at 136 mmol/L. Lower concentration are hypothesized to indicate perforated acute appendicitis.
1 secondary outcome
Plasma sodium concentration adding precision to the diagnostic performance of "the Appendicitis Inflammatory Response (AIR) score".
Time frame: Diagnostic values of interest are only obtained at one occasion on admission to the emergency department
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 27 Nov 2024.
- Background: PubMed 17968164Andersson RE, Petzold MG. Nonsurgical treatment of appendiceal abscess or phlegmon: a systematic review and meta-analysis. Ann Surg. 2007 Nov;246(5):741-8. doi: 10.1097/SLA.0b013e31811f3f9f.
- Background: PubMed 31022754Lindestam U, Almstrom M, Jacks J, Malmquist P, Lonnqvist PA, Jensen BL, Carlstrom M, Krmar RT, Svensson JF, Norberg A, Flaring U. Low Plasma Sodium Concentration Predicts Perforated Acute Appendicitis in Children: A Prospective Diagnostic Accuracy Study. Eur J Pediatr Surg. 2020 Aug;30(4):350-356. doi: 10.1055/s-0039-1687870. Epub 2019 Apr 25.
- Background: PubMed 33153722Pogorelic Z, Luksic B, Nincevic S, Luksic B, Polasek O. Hyponatremia as a predictor of perforated acute appendicitis in pediatric population: A prospective study. J Pediatr Surg. 2021 Oct;56(10):1816-1821. doi: 10.1016/j.jpedsurg.2020.09.066. Epub 2020 Oct 8.
- Background: PubMed 25727811Scott AJ, Mason SE, Arunakirinathan M, Reissis Y, Kinross JM, Smith JJ. Risk stratification by the Appendicitis Inflammatory Response score to guide decision-making in patients with suspected appendicitis. Br J Surg. 2015 Apr;102(5):563-72. doi: 10.1002/bjs.9773. Epub 2015 Mar 2.
- AnderssonLink provided by the sponsor.
- LindestamLink provided by the sponsor.
- PogorelicLink provided by the sponsor.
- ScottLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. It is likely that we will share data on request when the study is published,
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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.
Urban Fläring, Ass Prof principal investigator
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Appendicitis and Children, Only, run by Urban Fläring at 1 site in Sweden.
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 1 inclusion and 2 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 27 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Plasma sodium concentration as a predictor for perforated acute appendicitis. (time frame: Possible predictive variables will only be obtained at one occation on the day of admission to the emergency department.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04806789, which also lists 4 linked publications.
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 27 Nov 2024.