Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000219785
Ethics application status
Approved
Date submitted
5/04/2020
Date registered
8/02/2022
Date last updated
8/02/2022
Date data sharing statement initially provided
8/02/2022
Date results information initially provided
8/02/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Association between hyponatremia and severe Necrotising enterocolitis in newborn infants
Scientific title
Cohort study on hyponatremia and risk for bowel ischemia or death in infants with Necrotising enterocolitis
Secondary ID [1] 306363 0
None
Universal Trial Number (UTN)
Trial acronym
NaNEC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
necrotising enterocolitis 316960 0
surgical necrotising enterocolitis 316961 0
hyponatremia 320941 0
Condition category
Condition code
Oral and Gastrointestinal 315115 315115 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Surgery 315116 315116 0 0
Other surgery
Infection 318746 318746 0 0
Other infectious diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The presence of plasmatic hyponatremia or a decrease in plasmatic sodium at first symptoms in infants with Necrotising enterocolitis during their staying in the neonatal ward.
Retrospective cohort study, no active participation, only data from medical records collected for the study. All patients from the Stockholm County who received a NEC diagnosis (P77.9 according to ICD-10) from 1st of January 2009 to 31st of December 2014 were identified in the Swedish Neonatal Quality Register (SNQ). All infants who present with Necrotising enterocolitis will be assessed for 2 weeks from NEC diagnosis. Patients' records are examined, based on established clinical and radiological criteria, to check the accuracy of the diagnosis. NEC diagnosis was based on clinical signs plus the presence of intramural gas/portal gas on abdominal radiographs and/or histological evidence of NEC.
Intervention code [1] 317265 0
Diagnosis / Prognosis
Comparator / control treatment
It is a cohort study on infants with NEC, there is no control group as such but we are going to compare those who are going to need surgery/ died to those with medical NEC
Control group
Active

Outcomes
Primary outcome [1] 323393 0
Primary outcome was severe Necrotizing enterocolitis (NEC), defined as the need for intestinal resection because of bowel necrosis/ischemia and/or NEC-related death within 2 weeks of the onset of NEC. NEC related death was defined as such after reviewing the pathology report from either autopsy or surgical specimen.
Timepoint [1] 323393 0
2 weeks from symptoms when the clinician suspected NEC, obtained blood samples from the infants and started medical treatment (fasting and antibiotics).
Primary outcome [2] 323394 0
Primary outcome was severe Necrotizing enterocolitis (NEC), defined as the need for intestinal resection because of bowel necrosis/ischemia and/or NEC-related death within 2 weeks of the onset of NEC in infants without pneumoperitoneum at the radiography. NEC related death was defined as such after reviewing the pathology report from either autopsy or surgical specimen.
Timepoint [2] 323394 0
2 weeks from symptoms when the clinician suspected NEC, obtained blood samples from the infants and started medical treatment (fasting and antibiotics).
Secondary outcome [1] 399831 0
To assess if sodium difference is associated with higher risk of severe NEC (bowel necrosis/perforation and/or death because of NEC in 14 days from symptoms) in infants without radiological indication for surgery ( pneumoperitoneum).
Timepoint [1] 399831 0
2 weeks from symptoms when the clinician suspected NEC, obtained blood samples from the infants and started medical treatment (fasting and antibiotics).

Eligibility
Key inclusion criteria
_Patients from the Stockholm County Council (SLL) who received NEC diagnosis, ICD-10 P77.9 A-X, from 2009 through 2014 are eligibile for the study

- Only Patients with a confirmed NEC diagnosis (based on clinical signs plus the presence of intramural gas/portal gas on abdominal radiographs and/or histological evidence of NEC) were included.


Minimum age
2 Days
Maximum age
90 Days
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Infants with uncertain diagnosis of NEC (Bell´s stage <II) were not considered having NEC and excluded from the study

- infants with major abdominal malformations

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Retrospective cohort study. The cohort (n= 89 infants) was already establish. For our primary outcome We calculate a sample size of 58 patients assuming a Relative risk of 2 and a prevalence of exposure around 35% in this population, even assuming the possibility of missing data up to 25% the cohort was large enough for the purpose.
We are going to collect data from blood samples on metabolic status ( sodium, creatinine, lactate, glucose) from a 3 days before diagnosis NEC to surgery because of NEC from journal charts. We are going to calculate the sodium difference ( = plasmatic sodium from 1-3 days before diagnosis – plasmatic sodium at first symptoms).
Primary outcome: To assess if hyponatremia ( Sodium < 135 mmol/l) and sodium difference is associated with higher risk of severe NEC (bowel necrosis/perforation and/or death because of NEC in 14 days from symptoms)
Secondary outcome: To assess if hyponatremia ( Sodium < 135 mmol/l) and sodium difference is associated with higher risk of severe NEC (bowel necrosis/perforation and/or death because of NEC in 14 days from symptoms) in infants without a radiological indication ( pneumoperitoneum) for surgery.
We are going to draw a Directed Acyclic Graph to study the eventual confounders. Then we are going to calculate the odds ratio for our primary and secondary outcome using logistic regression. We are going to adjust our model for possible confounders.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
2/03/2020
Date of last participant enrolment
Anticipated
Actual
5/11/2020
Date of last data collection
Anticipated
Actual
5/11/2020
Sample size
Target
89
Accrual to date
Final
89
Recruitment outside Australia
Country [1] 22468 0
Sweden
State/province [1] 22468 0
Stockholm

Funding & Sponsors
Funding source category [1] 305388 0
Hospital
Name [1] 305388 0
Karolinska Univerisity Hospital
Country [1] 305388 0
Sweden
Primary sponsor type
Hospital
Name
Karolinska University Hospital
Address
Universitetssjukhuset, Eugeniavägen 3, 171 76 Solna Stockholm
Country
Sweden
Secondary sponsor category [1] 305773 0
None
Name [1] 305773 0
None
Address [1] 305773 0
None
Country [1] 305773 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305719 0
Etikprövningsmyndighet
Ethics committee address [1] 305719 0
Etikprövningsmyndigheten
Box 2110
750 02 Uppsala
Ethics committee country [1] 305719 0
Sweden
Date submitted for ethics approval [1] 305719 0
12/12/2019
Approval date [1] 305719 0
05/02/2020
Ethics approval number [1] 305719 0
2019-06289

Summary
Brief summary
Our hypothesis is that a drop in plasmatic sodium at the onset of necrotising enterocolitis in neonates is associated with higher risk of ischemic/perforated bowel and therefore with the severity of the disease.
We are going to performed a retrospective cohort study. We are going to collect data on patients who developed necrotising enterocolitis from 2009-2014 in SLL.. Patients' records are examined, based on established clinical and radiological criteria, to check the accuracy of the diagnosis. NEC diagnosis was based on clinical signs plus the presence of intramural gas/portal gas on abdominal radiographs and/or histological evidence of NEC. Infants with uncertain diagnosis of NEC (Bell´s stage <II) were not considered having NEC.
We are going to collect data from blood samples on metabolic status ( sodium, creatinine, lactate, glucose) from a 3 days before diagnosis NEC to surgery because of NEC from journal charts. We are going to calculate the sodium difference ( = plasmatic sodium from 1-3 days before diagnosis – plasmatic sodium at first symptoms).
Primary outcome: To assess if sodium difference is associated with severe NEC (bowel necrosis/perforation and/or death because of NEC in 14 days from symptoms)
Secondary outcome: To assess if sodium difference is associated with severe NEC (bowel necrosis/perforation and/or death because of NEC in 14 days from symptoms) in infants without radiological indication for surgery (pneumoperitoneum). Results are going to be presented as odds ration
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101342 0
Mrs Elena Palleri
Address 101342 0
Department of Neonatology

Karolinska University Hospital
Solnavägen 1, 171 77 Solna, Stockholm
Sweden
Country 101342 0
Sweden
Phone 101342 0
+46732115521
Fax 101342 0
Email 101342 0
[email protected]
Contact person for public queries
Name 101343 0
Mrs Elena Palleri
Address 101343 0
Department of Neonatology

Karolinska University Hospital
Solnavägen 1, 171 77 Solna, Stockholm
Sweden
Country 101343 0
Sweden
Phone 101343 0
+46732115521
Fax 101343 0
Email 101343 0
[email protected]
Contact person for scientific queries
Name 101344 0
Prof Tomas Wester
Address 101344 0
Prof Tomas Wester
K6 Kvinnors och barns hälsa, K6 Barnonkologi och Barnkirugi
Solnavägen 1,, 171 77 Stockholm

Sweden
Country 101344 0
Sweden
Phone 101344 0
+46706847187
Fax 101344 0
Sweden
Email 101344 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
the final dataset with de-identified participant data of published results only
When will data be available (start and end dates)?
Beginning 3 months and ending 2 years following main results publication
Available to whom?
Researchers upon request
Available for what types of analyses?
only for meta-analysis
How or where can data be obtained?
upon request to the correspondent authors:
mail: [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.