NEC Screening Abdominal Radiograph vs Bowel Ultrasound in Preemies

NCT ID: NCT03963011

Last Updated: 2022-01-10

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-20

Study Completion Date

2020-10-01

Brief Summary

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The overall primary objective is to establish the feasibility and pilot the design and delivery of a diagnostic randomized controlled trial (RCT) of BUS (bowel ultrasound) for NEC evaluation which will lead to a successful application for a larger, multi-center clinical trial in the future. This program of research is anticipated to have a significant positive impact in the timely and accurate diagnosis of NEC in preterm infants.

Detailed Description

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Necrotizing enterocolitis (NEC) is the most common bowel disease in premature and low birth weight neonates. NEC is defined by the loss of mucosal integrity of the bowel wall enabling bacteria and other toxins to permeate into the bowel causing ischemia and necrosis which can lead to bowel perforation and sepsis. NEC can result in substantial morbidity and mortality and prolonged hospital stay.

In the past, abdominal radiography has been scored on a standard scale that correlated with outcomes. Duke University Medical Center developed a standardized ten-point radiographic scale, the Duke Abdominal Assessment Scale (DAAS) (Appendix B) and was proven to be directly proportional to the severity of NEC on patients that underwent surgery. Abdominal radiographs are assessed for gas pattern, bowel distention, location and features, pneumatosis (gas in bowel wall), portal venous gas, and pneumoperitoneum (free air in peritoneal cavity) to indicate the level of suspicion of NEC. The use of abdominal radiographs is the most common assessment for suspected NEC in infants, however, there have been recent studies done on the utility of bowel ultrasound to aid in early diagnosis of NEC due to the ability to evaluate peristalsis, echogenicity and thickness of bowel wall, pneumatosis and the capability of doing color Doppler to evaluate blood perfusion. A University of Toronto study used ultrasound to assess bowel perfusion with color Doppler in neonates and found a correlation between absence of bowel wall perfusion and the increased severity of NEC on surgical pathology. Although there are similar signs found between abdominal radiography and bowel ultrasound, some of the more severe features such as, pneumoperitoneum, were found to be more sensitive on bowel ultrasound, thus potentially leading to more definitive treatment. Currently, there is no good study evaluating whether the use of bowel ultrasound affects clinical outcomes in VLBW patients over the use of abdominal radiography alone.

The use bowel ultrasound has yet to be adopted in the setting of suspicion for NEC at our institution. This is primarily due to the lack of expertise of the ultrasound technologists, radiologists and clinicians. With literature dating back to 2005 supporting the use of bowel ultrasound in diagnosis of severity of NEC, we would like to see if a regimen involving combined ultrasound and radiograph screening for NEC would make a difference in clinical outcomes (morbidity, mortality, and length of stay (LOS)) compared with radiograph screening alone.

Calprotectin is a protein found in the stool that, at elevated levels, indicates gastrointestinal inflammation. The addition of fecal biomarkers to the diagnostic work up for NEC also has promising impact. It has been suggested that fecal calprotectin levels obtained at the time of suspicion of NEC may be a useful noninvasive indicator to determine the severity of inflammation in the intestine and whether it is related to NEC or other forms of inflammation. Correlation of the fecal biomarkers with findings on BUS may be helpful to more definitively diagnose NEC.

Conditions

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Enterocolitis, Necrotizing Premature Infant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Infants randomized to the AXR only arm will obtain an AXR as per standard of care. Repeat AXR, if any, will be left to the discretion of the treating neonatologist. In this arm, no BUS study will be performed unless the attending neonatologist decides it is clinically indicated. This situation is expected to be exceedingly rare, as BUS is not part of the standard of care for NEC evaluation. Infants randomized to the AXR and BUS arm will also get an AXR, with repeat AXR left to the discretion of the treating neonatologist. In addition to this standard of care, infants randomized to this arm will receive a BUS as the intervention. This BUS will be ordered at the same time as the initial AXR and will be performed within six hours of the order being placed.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Arm A: AXR Only

Infants randomized to Arm A will obtain an abdominal x-ray (AXR) as per standard of care

Group Type NO_INTERVENTION

No interventions assigned to this group

Arm B: AXR + Bowel US

Infants randomized to Arm B will obtain an abdominal x-ray (AXR) as per standard of care and a bowel ultrasound (BUS) as the intervention

Group Type ACTIVE_COMPARATOR

Bowel Ultrasound

Intervention Type DIAGNOSTIC_TEST

Ultrasound imaging of the bowel

Interventions

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Bowel Ultrasound

Ultrasound imaging of the bowel

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* • Neonates born prior to or at 28 weeks gestation admitted to NICU at CMH

Exclusion Criteria

* Infants with chromosomal or multiple congenital anomalies
* Unable to ultrasound the bowel (e.g. gut in silo, omphalocele, gastroschisis)
* Infants who are greater than 36 corrected weeks upon admission
Maximum Eligible Age

28 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Mercy Hospital Kansas City

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Erin Opfer, DO

Role: PRINCIPAL_INVESTIGATOR

Children's Mercy Hospital Kansas City

Locations

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Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Countries

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United States

References

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Epelman M, Daneman A, Navarro OM, Morag I, Moore AM, Kim JH, Faingold R, Taylor G, Gerstle JT. Necrotizing enterocolitis: review of state-of-the-art imaging findings with pathologic correlation. Radiographics. 2007 Mar-Apr;27(2):285-305. doi: 10.1148/rg.272055098.

Reference Type BACKGROUND
PMID: 17374854 (View on PubMed)

Staryszak J, Stopa J, Kucharska-Miasik I, Osuchowska M, Guz W, Blaz W. Usefulness of ultrasound examinations in the diagnostics of necrotizing enterocolitis. Pol J Radiol. 2015 Jan 1;80:1-9. doi: 10.12659/PJR.890539. eCollection 2015.

Reference Type BACKGROUND
PMID: 25574248 (View on PubMed)

Coursey CA, Hollingsworth CL, Gaca AM, Maxfield C, Delong D, Bisset G 3rd. Radiologists' agreement when using a 10-point scale to report abdominal radiographic findings of necrotizing enterocolitis in neonates and infants. AJR Am J Roentgenol. 2008 Jul;191(1):190-7. doi: 10.2214/ajr.07.3558.

Reference Type BACKGROUND
PMID: 18562745 (View on PubMed)

Coursey CA, Hollingsworth CL, Wriston C, Beam C, Rice H, Bisset G 3rd. Radiographic predictors of disease severity in neonates and infants with necrotizing enterocolitis. AJR Am J Roentgenol. 2009 Nov;193(5):1408-13. doi: 10.2214/AJR.08.2306.

Reference Type BACKGROUND
PMID: 19843760 (View on PubMed)

Faingold R, Daneman A, Tomlinson G, Babyn PS, Manson DE, Mohanta A, Moore AM, Hellmann J, Smith C, Gerstle T, Kim JH. Necrotizing enterocolitis: assessment of bowel viability with color doppler US. Radiology. 2005 May;235(2):587-94. doi: 10.1148/radiol.2352031718.

Reference Type BACKGROUND
PMID: 15858098 (View on PubMed)

Kim WY, Kim WS, Kim IO, Kwon TH, Chang W, Lee EK. Sonographic evaluation of neonates with early-stage necrotizing enterocolitis. Pediatr Radiol. 2005 Nov;35(11):1056-61. doi: 10.1007/s00247-005-1533-4. Epub 2005 Aug 3.

Reference Type BACKGROUND
PMID: 16078076 (View on PubMed)

Nakayuenyongsuk W, Christofferson M, Stevenson DK, Sylvester K, Lee HC, Park KT. Point-of-Care Fecal Calprotectin Monitoring in Preterm Infants at Risk for Necrotizing Enterocolitis. J Pediatr. 2018 May;196:98-103.e1. doi: 10.1016/j.jpeds.2017.12.069. Epub 2018 Mar 6.

Reference Type BACKGROUND
PMID: 29519542 (View on PubMed)

Cuna A, Chan S, Jones J, Sien M, Robinson A, Rao K, Opfer E. Feasibility and acceptability of a diagnostic randomized clinical trial of bowel ultrasound in infants with suspected necrotizing enterocolitis. Eur J Pediatr. 2022 Aug;181(8):3211-3215. doi: 10.1007/s00431-022-04526-4. Epub 2022 Jun 17.

Reference Type DERIVED
PMID: 35713688 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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17030157

Identifier Type: -

Identifier Source: org_study_id

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