Clinical trial NCT05307419: Full Thickness vs. Rectal Suction Biopsy in the Diagnosis of Hirschsprungs Disease
Official title: Prospective Randomised Blinded Study Comparing Full Thickness Biopsy and Rectal Suction Biopsies in the Diagnosis of Mb: Hirschsprung
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hirschsprung Disease
Keywords: Hirschsprungs disease
Rectal biopsy
Rectal suction biopsy
Full thickness biopsy
Randomised
Blinded
Mb. Hirschsprung
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
First posted: 2022-04-01
Enrollment: 300
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective randomized blinded case-control study.
Primary purpose: DIAGNOSTIC

Brief summary: The objective of this prospective study is to compare the diagnostic accuracy of rectal suction biopsy (RSB) compared to full thickness rectal biopsy (FTB) in the diagnosis of Hirschsprungs Disease (HD) in children. The secondary objective to compare cost-effectiveness of the two procedures

Detailed description: Diagnostic procedures involving the need of surgically obtaining tissue material, carry the risk of complications and the risk of being inconclusive due to various reasons. Lowering the risk of inconclusive diagnostic tests with highest sensitivity and specificity is of high importance in all diagnostic procedures.

A full thickness rectal biopsy (FTB) includes both the submucosal and the myenteric nerve plexus for histological evaluation for presence of ganglion cells and hypertrophic nerve fibers. FTB is performed in general anesthesia (GA), the biopsy is cut with scissors under direct visualization of the intestine and with suturing of the biopsy defect. The other method is a suction biopsy (RSB) in which the biopsy is more superficial acquiring only the submucosal layers. RSB's are performed with a specially designed rectoscope, and the biopsy is obtained under negative pressure within the scope, without visual guidance. This procedure can be performed without anesthesia in children blow 1 year and does not necessitate suturing of the bowel.

The problem with especially RSB could be that the biopsy is too superficial or too small in size for proper pathological evaluation. As a consequence the child has to undergo a new procedure. There is also the risk of false positive or false negative results, which is a serious clinical issue carrying the risk of performing extensive surgery in an otherwise healthy child.

Inconclusive biopsies differ extensively from series to series. But the two largest studies show a rate of inconclusive biopsies at 10% for RSB and 5% for FTB.(Freidmacher and Bjorn). The biopsy profile is similar with less than 1% severe complications (Above Clavien DindoIII) in both procedures, with bleeding as dominating in RSB and Fever in FTB.

Thus there are different advantages and disadvantages between the two methods of biopsy in children suspicious of HD, and different centers advocate either. A prospective comparison of both methods with the child as its own control is a more precise way to compare the two methods and has never been performed. Thus, this study is expected to give an answer to an important research question that will have potential implication worldwide.

Hypothesis:

Our hypothesis is that FTB has lower rate of inconclusive biopsies compared to RSB in the diagnosis of HD.

Design:

Prospective, biopsy sample randomised study.

Method:

Patients referred for rectal biopsy at Odense University Hospital on the suspicion of HD will undergo both an FTB and RSB performed under GA in the same procedure.

Patients will be randomised to which biopsy will be examined first at the pathology department. If a diagnosis can bed securely made on the first tissue samples the other biopsy materials will be stores for examination by another pathologist 30 days later. If any nerve cell is present the sample is negative for Mb. Hirschsprung. If no nervecells is present the biopsy the patient is positive for mb. Hirschsprung. If the tissue is evaluated as not suitable for diagnosis the sample is inconclusive. If the sample is inconclusive the tissue from the other biopsy method is evaluated immediately to secure a fast diagnosis.

All children between 0-15 years of age undergoing biopsies for diagnosis of the diagnosis of HD in Western Denmark from 1/9 2020 will be offered to participate and parental accept will be acquired.

Cost-effectiveness will be measured upon with data from pathology cost and surgery utensils cost.

These will be compared between the two groups.

Power calculation:

With the assumption of a 5 % inconclusive rate for FTB and 10% for RSB (2,5) a McNemar's test for matched comparison of dichotomous outcome (inconclusive / conclusive) indicates the need for 282 patients to obtain 70% strength and a significance level of 5%. (P-value 0.05).

These calculations are based on the largest numbers of biopsy evaluations in the literature.

In these publications a rate of 5% inconclusive biopsies at FTB and 10% at RSB are found.

Interim analyse will be performed after 25%, 50% and 75%. Above 8% complications on 30-day follow-up will result in the study will be paused and examinations of the complications will be performed.

Eligibility criteria: Inclusion Criteria:

* Patients that are referred for rectal biopsy for suspected HD, age 0-15 years.
* Written informed consent of the parents or guardian.

Exclusion Criteria:

* Lack of consent from parents or guardians.
* Previous surgery on the ano-rectum e.g. crohns disease and/or fistulas

Primary outcomes:
measure: Number of inconclusive biopsies between FTB and RSB.
timeFrame: 30 days
Secondary outcomes:
measure: Surgical and pathology cost.
timeFrame: 30 days
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Odense University Hospital
state: Fyn
Study officials:
affiliation: University of Southern Denmark
name: Mark mr Ellebaek, Dr
role: STUDY_DIRECTOR
affiliation: Odense University Hospital
name: Rasmus mr Nielsen, Dr
role: STUDY_CHAIR
affiliation: Odense University Hospital
name: Gunvor ms Madsen, Dr
role: STUDY_CHAIR
affiliation: Odense University Hospital
name: Niels mr Bjorn, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Odense University Hospital
name: Lene ms Christensen, Dr
role: STUDY_CHAIR
References:
citation: Muise ED, Hardee S, Morotti RA, Cowles RA. A comparison of suction and full-thickness rectal biopsy in children. J Surg Res. 2016 Mar;201(1):149-55. doi: 10.1016/j.jss.2015.10.031. Epub 2015 Oct 28.
citation: Bjorn N, Rasmussen L, Qvist N, Detlefsen S, Ellebaek MB. Full-thickness rectal biopsy in children suspicious for Hirschsprung's disease is safe and yields a low number of insufficient biopsies. J Pediatr Surg. 2018 Oct;53(10):1942-1944. doi: 10.1016/j.jpedsurg.2018.01.005. Epub 2018 Jan 31.
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