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Trial registered on ANZCTR


Registration number
ACTRN12618000741280
Ethics application status
Approved
Date submitted
26/04/2018
Date registered
3/05/2018
Date last updated
3/05/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Reliability of symptoms, blood and stool markers in predicting extent of bowel ulceration in children with Crohns
Scientific title
Reliability of clinical symptoms and biomarkers in predicting endoscopic disease outcomes in children with Crohns Disease
Secondary ID [1] 294725 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's disease 307604 0
Condition category
Condition code
Oral and Gastrointestinal 306661 306661 0 0
Crohn's disease

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
All children with suspected CD routinely undergo clinical, laboratory and endoscopic assessment at diagnosis. Follow up clinical and laboratory tests (both blood and faecal markers) are also part of routine clinical service delivery. Confirmation of mucosal healing with repeat endoscopy is already integrated into our clinical practice and remains the commonest indication (~35%) for colonoscopy in children attending PMH. Therefore, the only investigational intervention of our proposed study is to ensure symptoms based score; stool and serum biomarkers are performed opportunistically within two weeks of clinically indicated endoscopy and an independent, central, blinded review of endoscopy images.
Intervention code [1] 301017 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305670 0
To compare performance of PCDAI with simple endoscopic disease score (SES-CD) in children with CD undergoing elective endoscopy at diagnosis and during maintenance therapy.
Timepoint [1] 305670 0
At the time of clinically indicated endoscopy during initial diagnosis and any time during maintenance phase of treatment.
Primary outcome [2] 305709 0
To compareperformance of CRP with simple endoscopic disease score (SES-CD) in children with CD undergoing elective endoscopy at diagnosis and during maintenance therapy.

Timepoint [2] 305709 0
At the time of clinically indicated endoscopy during initial diagnosis and any time during maintenance phase of treatment.
Primary outcome [3] 305710 0
To compare performance of FC with simple endoscopic disease score (SES-CD) in children with CD undergoing elective endoscopy at diagnosis and during maintenance therapy.
Timepoint [3] 305710 0
At the time of clinically indicated endoscopy during initial diagnosis and any time during maintenance phase of treatment.
Secondary outcome [1] 346111 0
To prospectively validate the reliability of a composite score (PCDAI equal to 10, CRPless than 5mg/dl and FC less than 500 µgram/gm or 50% drop from baseline FC whichever is less) in predicting mucosal healing, defined as simple endoscopic score for CD (SES-CD equal to 0-2) in children undergoing repeat endoscopy.
Timepoint [1] 346111 0
At the time of clinically indicated endoscopy during initial diagnosis and any time during maintenance phase of treatment.
Secondary outcome [2] 346158 0
Validate performance of Mini index in predicting endoscopic disease activity as defined by simple endoscopic score for CD.
Timepoint [2] 346158 0
At the time of clinically indicated endoscopy during initial diagnosis and any time during maintenance phase of treatment.

Eligibility
Key inclusion criteria
We expect to prospectively enrol 120 children with either new diagnosis or established CD (2-17 years) from two participating Children’s Hospital (Princess Margaret Hospital for children and Lady Cilento Children’s Hospital, Brisbane).
Enrolled patients will be asked to provide routine blood and faecal samples for assessment of biomarkers (CRP, FC) to assess treatment response within two weeks of the scheduled colonoscopy. Endoscopic disease activity will be scored using a validated simple endoscopic score for Crohn's disease at the time of procedure and de-identified images will be evaluated by an independent, central, blinded review process.
Minimum age
2 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Children younger than 2 years (Very early onset IBD), patients with incomplete colonoscopy, inability to deliver the blood and stool sample within 2 weeks of colonoscopy and proven infectious ileocolitis (positive stool culture for salmonella/shigella etc) will be excluded from the study.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
It is estimated, from anecdotal clinical evidence, that approximately 70% of CD patients undergoing an endoscopy will be determined to have active CD – meaning 30% of CD patients will have inactive CD and thus will have undergone an endoscopy that was presumably unnecessary. Assuming a null hypothesis that the area under the curve (AUC) will be 0.65, a sample of 120 participants will provide over 85% power to detect an alternative AUC of 0.8 or more, assuming alpha of 0.05. Within the active CD group, it is estimated that 42% of participants will be classified as mild (an SES-CD score of 3-10) and 58% will be classified as moderate or severe (an SES-CD score of >=11). Again, assuming a null hypothesis that the area AUC for classifying the active group into mild vs ‘moderate or severe’ will be 0.65, a sample of 84 participants (within this subgroup) will provide over 75% power to detect an alternative AUC of 0.8 or more, assuming alpha of 0.05.
ROC curve analysis will be performed to, in turn, assess the discriminative ability of the continuous measures FC, CRP, and PCDAI, with sensitivity, specificity, positive predictive value, and negative predictive value calculated for the optimal diagnostic cut points (determined by examining the output from the ROC analysis).

As additional exploratory research, both logistic regression and ordinal logistic regression will be used to examine the combined ability of FC, CRP and PCDAI to predict IBS status (inactive/active) and classification (inactive/mild/moderate/severe) respectively.
In addition to presenting odds ratios and 95% confidence intervals, the individual predictions from each model will be compared with the gold standard endoscopy assessment, across a range of probability thresholds, to calculate sensitivity and specificity as a means to determine model efficacy. Variables considered for inclusion in the modelling, in addition to study site, include sex, age of CD diagnosis, disease location, and disease behaviour / duration.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
15/02/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2019
Actual
Sample size
Target
120
Accrual to date
12
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 10794 0
Princess Margaret Hospital - Subiaco
Recruitment hospital [2] 10795 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 22533 0
6008 - Subiaco
Recruitment postcode(s) [2] 22534 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 299333 0
Hospital
Name [1] 299333 0
Princess Margaret Hospital Foundation
Country [1] 299333 0
Australia
Primary sponsor type
Hospital
Name
Princess Margaret Hospital Foundation
Address
Level 6 Hay Street Building, Subiaco WA 6008
Country
Australia
Secondary sponsor category [1] 298600 0
None
Name [1] 298600 0
Address [1] 298600 0
Country [1] 298600 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300238 0
HREC Princess margaret hospital
Ethics committee address [1] 300238 0
Ethics committee country [1] 300238 0
Australia
Date submitted for ethics approval [1] 300238 0
08/06/2017
Approval date [1] 300238 0
17/11/2017
Ethics approval number [1] 300238 0
HREC Ref. 2016045EP

Summary
Brief summary
In a previous small single centre study of twenty four children with new diagnosis CD, we confirmed symptoms based score alone (PCDAI) was unreliable, blood test (CRP) had moderate utility and stool biomarkers (FC) had the best individual utility in predicting endoscopic mucosal healing. We also demonstrated that combination of PCDAI less than10, CRP less than 5mg/dl and FC less than 500 µgram/gm has greater accuracy identifying mucosal healing (SES-CD equal to 0-2) following standard EEN or Steroid induction therapy with specificity of 85% and positive like hood ratio 5.3. The reliability of this composite score (PCDAI less than 10, CRP less than 5mg/dl and FC less than 500 µgram/gm) in this small pilot study needs further validation in a larger prospective multicentre cohort study. To overcome limitations of this pilot study, we also want to extend this study to include; children with established CD experiencing clinical relapse, those in clinical remission with raised surrogate biomarkers (CRP more than 5mg/L and/or FC more than 250 µgram /gm of stool) and confirming mucosal healing in those with normal surrogate markers (CRP less than 5mg/L and FC less than 250 µgram /gm of stool and no symptoms. Our hypothesis is that establishing reliability of this composite index in predicting endoscopic healing in this mixed sample population will be useful both as a discriminative tool (for distinguishing active (SES-CD equal to 3) vs. inactive inflammation (SES-CD equal to 0-2) and evaluative tool (for defining treatment success).
Trial website
None
Trial related presentations / publications
Public notes
Attachments [1] 2633 2633 0 0
/AnzctrAttachments/374989-SCIENTIFIC PROTOCOL FORM 4B VERSION 4 12 November 17.docx

Contacts
Principal investigator
Name 83014 0
Dr Zubin Grover
Address 83014 0
Princess Margaret Hospital for Children
Roberts Road
Subiaco 6008
Perth, Western Australia
Country 83014 0
Australia
Phone 83014 0
+61893402228
Fax 83014 0
Email 83014 0
[email protected]
Contact person for public queries
Name 83015 0
Dr Zubin Grover
Address 83015 0
Princess Margaret Hospital for Children
Roberts Road
Subiaco 6008
Perth, Western Australia
Country 83015 0
Australia
Phone 83015 0
+61893402228
Fax 83015 0
Email 83015 0
[email protected]
Contact person for scientific queries
Name 83016 0
Miss Ainslie Lopez
Address 83016 0
Clinical Nurse Specialist
Gastroenterology Department
Princess Margaret Hospital for Children
Subiaco 6008
Perth, Western Australia
Country 83016 0
Australia
Phone 83016 0
+61893402228
Fax 83016 0
Email 83016 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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