RBC Irradiation, Anemia and Gut Injury

NCT ID: NCT02741648

Last Updated: 2026-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

324 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-07-31

Study Completion Date

2026-02-28

Brief Summary

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The purpose of this trial is to study the effect that anemia and red blood cell (RBC) transfusions have on oxygen levels in the digestive tracts of extremely low birth weight (ELBW) infants and to look for possible markers in a baby's blood, urine and/or stool that may lead to a better understanding of what makes an ELBW infant at risk for digestive tract problems such as necrotizing enterocolitis.

Detailed Description

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Necrotizing Enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality in preterm infants. To date, no effective genetic or clinical markers exist to predict which premature infant will develop NEC, limiting targeted prevention strategies. Anemia and digestive tract complications are common problems in extremely low birth weight infants. Anemia is a condition in which the body does not have enough red blood cells (RBC). RBCs are important because they contain hemoglobin, the substance that carries oxygen throughout the body. Transfusions of RBCs in these infants is frequently required to correct the anemia.

Multiple observational studies have reported an association between the exposure to red blood cell (RBC) transfusion and the subsequent development of transfusion related-NEC (TR-NEC).However, no clinical studies have investigated the underlying pathophysiologic mechanisms of TR-NEC. In adults, prolonged RBC storage prior to transfusion has been associated with adverse outcomes and may also contribute to TR-NEC. However, the chronological storage age of blood may not be an accurate gauge of donor RBC function; irradiation of RBCs to prevent transfusion-associated graft-vs-host disease may also contribute to TR-NEC. Currently, the duration considered safe for RBC storage following irradiation (irradiation storage time (IST)) is unclear. Given the multifactorial etiology of NEC, preventative efforts will be more successful if clinicians understand the underlying pathophysiologic mechanisms and modifiable risk factors.

In this study the researchers will conduct a multicenter observational cohort study of very preterm (VPT) infants weighing ≤1250g at birth to prospectively investigate the associations between RBC transfusion, digestive tract oxygenation, and TR-NEC. The overarching hypothesis for this study is that irradiation of RBC units followed by prolonged storage perturbs RBC metabolism and function, and these derangements are associated with paradoxical microvascular vasoconstriction, tissue hypoxia and TR-NEC in transfused infants with already impaired gut oxygenation due to significant anemia. All RBC units transfused to VPT infants throughout the study will be stored based on current standard operating procedures per local site blood banking practices. There will be no study-specific approaches to transfusions or transfusion thresholds, and the decision to transfusion will be made as part of current clinical care by the treating clinicians. No study-specific blood draws will occur and all samples will be obtained from residual samples collected for clinical care that are to be discarded.

Oxygen levels in the digestive tract will be measured before, during and after each blood transfusion using a tissue oxygen monitor called Near Infrared Spectroscopy (NIRS). By using this technology, the researchers intend to better understand intestinal blood flow patterns. RBC function in RBC products transfused to infants will be compared between the infants who develop TR-NEC and matched control infants who do not develop TR-NEC. The researchers will explore the clinical implications of severe anemia when infants are 28 to 34 weeks of postmenstrual age, which is when infants are vulnerable to NEC.

Currently, there are no inexpensive, simple, patient/healthcare provider-operated hemoglobin tests available for diagnosing and assessing the degree of anemia without the use of a blood draw. To that end, Emory investigators have recently developed an algorithm that enables patients/healthcare providers to check if a patient is anemic by simply taking a picture of their fingernail beds on a Smartphone, and running the algorithm on a computer using MATLAB. These studies have shown that the degree of pallor in the fingernail beds, correlates with physiologic levels of hemoglobin in the blood and determines whether or not the patient is anemic. To date, the accuracy of this device has only been tested on adults and older children. Having an accurate and noninvasive means of testing for anemia in VPT infants would reduce the number of blood draws required, decrease the common side effects of phlebotomy, transfusion of RBCs, and would potentially be more cost-effective. As an additional study aim, the researchers of this study seek to develop a new image analysis algorithm (IAA) to predict hemoglobin level and anemia status from fingernail photos. The fingernail beds of VPT infants are extremely small and therefore it is uncertain if the nail bed is the most accurate site to assess anemia in these infants. To determine which site is most accurate in this population pictures will be taken of the fingernail beds, the toe nail beds, the palm of the hand and the sole of the foot with be photographed and analyzed.

Leftover samples of blood, urine, stool, and breast milk will be frozen, and stored and in the event a baby develops a digestive tract complication the samples will be studied in a laboratory to identify markers that indicate a healthy digestive tract versus illness. Immune cell function, digestive tract microbial changes, and serum cytokine levels will be compared between very preterm infants who develop NEC and those who do not.

Conditions

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Anemia Necrotizing Enterocolitis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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ELBW Infants without Irradiation Storage

Extremely Low Birth Weight Infants whose Red Blood Cell (RBC) transfusion did not have Irradiation Storage being tested with metabolomics profile.

Near Infrared Spectroscopy

Intervention Type DEVICE

INVOS 5100C Cerebral/Somatic Oximeter is an FDA-approved device used to measure renal and mesenteric tissue oxygenation, as defined by regional oxygenation saturation levels (rSO2). Two probe site monitoring will be used to evaluate differential tissue bed oxygenation. Adhesive sensor probes are applied to the periumbilical area for mesenteric monitoring and to the flank area for renal monitoring.

ELBW Infants Reaching the NEC Window

Extremely low birth weight infants who reach 28 to 34 postmenstrual week age, which is the NEC window.

Non-invasive Image-based Anemia Assessment

Intervention Type OTHER

A trained research associate will take 2 images (one with the camera flash on and one with the camera flash off) of the patient's fingernail beds, toe nail beds, palm of the hand and sole of the foot. Images will be taken within 24 hours, preceding, or following, each complete blood count (CBC) collection on each consented patient. The anemia diagnosing algorithm will then be run on the images.

ELBW Infants

Extremely low birth weight infants having intestinal microbial profiles examined via stool collected from discarded diapers, and immune cell function and serum cytokine levels examined using residual blood.

No interventions assigned to this group

ELBW Infants with Prolonged Irradiation Storage Time

Extremely Low Birth Weight Infants whose Red Blood Cell (RBC) transfusion had prolonged Irradiation Storage Time (IST) being tested with metabolomics profile.

Near Infrared Spectroscopy

Intervention Type DEVICE

INVOS 5100C Cerebral/Somatic Oximeter is an FDA-approved device used to measure renal and mesenteric tissue oxygenation, as defined by regional oxygenation saturation levels (rSO2). Two probe site monitoring will be used to evaluate differential tissue bed oxygenation. Adhesive sensor probes are applied to the periumbilical area for mesenteric monitoring and to the flank area for renal monitoring.

Interventions

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Near Infrared Spectroscopy

INVOS 5100C Cerebral/Somatic Oximeter is an FDA-approved device used to measure renal and mesenteric tissue oxygenation, as defined by regional oxygenation saturation levels (rSO2). Two probe site monitoring will be used to evaluate differential tissue bed oxygenation. Adhesive sensor probes are applied to the periumbilical area for mesenteric monitoring and to the flank area for renal monitoring.

Intervention Type DEVICE

Non-invasive Image-based Anemia Assessment

A trained research associate will take 2 images (one with the camera flash on and one with the camera flash off) of the patient's fingernail beds, toe nail beds, palm of the hand and sole of the foot. Images will be taken within 24 hours, preceding, or following, each complete blood count (CBC) collection on each consented patient. The anemia diagnosing algorithm will then be run on the images.

Intervention Type OTHER

Other Intervention Names

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NIRS

Eligibility Criteria

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Inclusion Criteria

* Birth weight ≤1250 grams
* Postnatal age within 7 days of birth

Exclusion Criteria

* Infant not expected to live beyond 7 days of life based on assessment of treating neonatologist
* Severe congenital abnormality expected to affect life expectancy
* RBC or platelet transfusion at an outside institution occurring prior to screening
* Maternal refusal to participate
Minimum Eligible Age

1 Day

Maximum Eligible Age

5 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role lead

Responsible Party

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Ravi Mangal Patel

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ravi Patel, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

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Grady Memorial Hospital

Atlanta, Georgia, United States

Site Status

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status

Northside Hospital - Neonatology

Atlanta, Georgia, United States

Site Status

Countries

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United States

References

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Marin T, Patel RM, Roback JD, Stowell SR, Guo Y, Easley K, Warnock M, Skvarich J, Josephson CD. Does red blood cell irradiation and/or anemia trigger intestinal injury in premature infants with birth weight </= 1250 g? An observational birth cohort study. BMC Pediatr. 2018 Aug 11;18(1):270. doi: 10.1186/s12887-018-1241-5.

Reference Type DERIVED
PMID: 30098602 (View on PubMed)

Other Identifiers

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2P01HL086773

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01HL138714

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2025P010798

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00083691

Identifier Type: -

Identifier Source: org_study_id

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