Clinical trial NCT01855347: Evaluation of Abdominal Tissue Oxygenation in Premature Infants Using Near Infrared Spectroscopy
Official title: Evaluation of Abdominal Tissue Oxygenation in Premature Infants Using Near Infrared Spectroscopy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Infant, Premature, Diseases
Hypoxia
Necrotizing Enterocolitis
Keywords: Prematurity
Hypoxia
Necrotizing Enterocolitis
Near Infrared Spectroscopy
Abdominal tissue oxygenation
NICU
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2013-05-16
Enrollment: 10
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Preterm infants (Premature Infants) from 32 to 36 weeks of post menstrual age hospitalized in the Neonatal Intensive Care Unit (NICU) at Brigham and Women's Hospital.

Brief summary: There is an increasing incidence of Necrotizing Enterocolitis (NEC) affecting the premature infant population, principally those with associated risk like extreme prematurity, extreme low birth weight, associated co-morbidities (Congenital heart disease, perinatal asphyxia) and those born in hospitals with limited resources for optimal neonatal care.

Near Infrared Spectroscopy (NIRS), has been used in premature infants to evaluate changes in cerebral perfusion and oxygenation. (1) It provides real time insight into the oxygen delivery.(3) In the premature patient population, many neurologic injuries occur as a result of prenatal (pre-existing) and/or postnatal disturbance on oxygen delivery. NIRS has been focused in cerebral monitoring. Light easily penetrates through neonatal bone and skin tissue, and allows to monitor the subjacent oxygen content. Early studies were performed to validate NIRS measurements and have established normative data.(4-6) The non-invasive method of monitoring cerebral hemodynamics and oxygenation has revolutionized the intensive care units in patients at risk for neurological injuries. This method has been successfully validated to monitor neonatal cerebral oxygenation in different clinical settings and study protocols. (7) NIRS provides non-invasive, continuous information on tissue perfusion and oxygen dynamics.

One of the biggest challenges of NEC spectrum diseases is in the making of early diagnosis. It is important to monitor not just cerebral perfusion but also the intestinal oxygenation.(8,9) Previous studies with NIRS have demonstrated that premature infants change their cerebral - splanchnic oxygenation ratios during feedings.(10) Guy et al. performed NIRS in premature piglets to demonstrate association of perfusion change with NEC spectrum(11,12); these studies suggest evidence that NIRS could be a useful diagnostic tool in the premature infant population trough abdominal NIRS (a-NIRS) measurement capable of detecting alterations in intestinal oxygenation and perfusion.

In summary, a-NIRS could be use in the premature infant population to define reference values, especially in patients at risk, which would then facilitate the early diagnosis of NEC spectrum diseases.

Detailed description: We will include, 10 premature infants from 32 to 36 weeks of post menstrual age, within the first week of life, that are clinically stable without diagnosis of Congenital Heart Disease, Necrotizing Enterocolitis, Sepsis or having been transfused less than three days before the evaluation. Infants with abdominal injuries, omphalocele, gastroschisis and abdominal skin irritation that does not permit the application of the probes will also be excluded.

10 premature infants from 32 to 36 weeks of post menstrual age will be included, after their first week of life, clinically stable status, and without diagnosis of Congenital Heart Disease, Necrotizing Enterocolitis, Sepsis or blood transfused less than three days before the moment of the evaluation. Infants with abdominal injuries, Omphalocele, Gastroschisis, skin irritation also will be excluded. NIRS device will record and monitor the Regional Oxygen Saturation (rSO2) in the infant during one week.

The evaluation will take place ar the Neonatal Intensive Care Unit (NICU), 6th floor at the Mary Horrigan Connors Center for Women's Health, Brigham and Women's Hospital. (http://www.brighamandwomens.org/newbornmedicine)

We will use a Near infrared spectroscopy (NIRS) device the INVOS 5100c (Covidien), catalogued under de Investigational Device Exemption (IDE) as 'non-significant risk device' (21 CFR 812.2) in order to perform monitoring as well as record-keeping with non-risk for the subject. No need Food and Drug Administration (FDA) clearance.

The application of the INVOS 5100c (Covidien) sensor optodes will be positioned in four locations (four channels), these will be in the lower abdomen, taking place bellow the umbilicus, with care, flush against the skin; in the submandibular region; upper left abdomen as well as in the thigh either left or right.

If the clinical status change during the monitoring, this could be discontinued under the criteria of the attending neonatologist in charge.

Once included, the sensors will be placed in the described areas and the team will reassure the quality of the lecture obtained. The rSO2 recordings will be continuously monitored for seven days, after this period of time, prospective observational following of patient data and outcomes will be implemented.

Clinical outcome data will be correlated with tissue oxygen saturation, other outcome variables will include length of NICU stay, morbidity, mortality, laboratory studies, oxygen saturation by standard pulse oximetry and continuous outcome variables will be analyzed using the Analysis of Variance (ANOVA) formula; mortality will be analyzed using Student's t-test. For the remaining variables (vital signs, lab values, oxygen saturation, morbidity, mortality), data will be extracted from clinical records and entered it into the electronic database.

The study staff, principal investigator, and co-investigators will identify potential subjects meeting the inclusion/exclusion criteria. Potential subjects will be identified by talking to the attending in charge at the NICU. Cases will be identified by communicating with the NIRS/NICU research team at Brigham and Women's Hospital.

Informed consent will be obtained from the parent(s) or guardian(s) under the Research involving no greater than minimal risk condition (46.404) where at least one of the parents must provide the permission.

In all cases we will approach the attending physician of prospective subjects to describe the study and obtain verbal consent to approach patients for recruitment; the attending physician or medical staff caring for the patient will be the first to make contact with the patients parents or guardian to describe the study briefly and ask permission for us to explain the study in more detail.

A review of the data will be conducted by a physician and a clinical review team. The principal investigator and study staff will be constantly monitoring and reviewing the rights, safety and welfare of all subjects in this trial through out the study.

In addition, the principal investigator will review any adverse events and report in accordance with the Partners Human Research Committees (PHRC) regulations.

Eligibility criteria: Inclusion Criteria:

* Preterm infant (32 to 36 weeks of postmenstrual age)
* Neonatal intensive care unit (NICU) patient
* Stable clinical condition (i.e. Vital signs, Hemodynamics)
* Age less than 6 weeks of life

Exclusion Criteria:

* Congenital Heart Disease
* Necrotizing enterocolitis prior to inclusion
* Non stable clinical condition
* Blood transfused less than three days prior to inclusion
* Abdominal injuries (i.e. Omphalocele, Gastroschisis, Skin irritation) that impedes placement of the optodes

Primary outcomes:
measure: Abdominal Tissue Oxygenation in Preterm Infant
timeFrame: 5 days
Secondary outcomes:
measure: Submandibular Tissue Oxygenation in Preterm Infant
timeFrame: 5 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital Newborn Medicine Department
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Ricardo Castillo-Galvan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Maxwell Weinmann, MD
role: STUDY_CHAIR
affiliation: Brigham and Women's Hospital
name: Steven A Ringer, MD, PhD
role: STUDY_DIRECTOR
affiliation: Brigham and Women's Hospital
name: Edward Kelly, MD
role: STUDY_CHAIR
References:
citation: Wolfberg AJ, du Plessis AJ. Near-infrared spectroscopy in the fetus and neonate. Clin Perinatol. 2006 Sep;33(3):707-28, viii. doi: 10.1016/j.clp.2006.06.010.
citation: Pellicer A, Bravo Mdel C. Near-infrared spectroscopy: a methodology-focused review. Semin Fetal Neonatal Med. 2011 Feb;16(1):42-9. doi: 10.1016/j.siny.2010.05.003. Epub 2010 Jun 26.
citation: Weiss M, Schulz G, Fasnacht M, Balmer C, Fischer JE, Gerber AC, Bucher HU, Baenziger O. Transcutaneously measured near-infrared spectroscopic liver tissue oxygenation does not correlate with hepatic venous oxygenation in children. Can J Anaesth. 2002 Oct;49(8):824-9. doi: 10.1007/BF03017416.
citation: Wolf M, Greisen G. Advances in near-infrared spectroscopy to study the brain of the preterm and term neonate. Clin Perinatol. 2009 Dec;36(4):807-34, vi. doi: 10.1016/j.clp.2009.07.007.
citation: Patel J, Marks K, Roberts I, Azzopardi D, Edwards AD. Measurement of cerebral blood flow in newborn infants using near infrared spectroscopy with indocyanine green. Pediatr Res. 1998 Jan;43(1):34-9. doi: 10.1203/00006450-199801000-00006.
citation: Yoxall CW, Weindling AM, Dawani NH, Peart I. Measurement of cerebral venous oxyhemoglobin saturation in children by near-infrared spectroscopy and partial jugular venous occlusion. Pediatr Res. 1995 Sep;38(3):319-23. doi: 10.1203/00006450-199509000-00008.
citation: Dominguez KM, Moss RL. Necrotizing enterocolitis. Clin Perinatol. 2012 Jun;39(2):387-401. doi: 10.1016/j.clp.2012.04.011. Epub 2012 May 18.
citation: Dave V, Brion LP, Campbell DE, Scheiner M, Raab C, Nafday SM. Splanchnic tissue oxygenation, but not brain tissue oxygenation, increases after feeds in stable preterm neonates tolerating full bolus orogastric feeding. J Perinatol. 2009 Mar;29(3):213-8. doi: 10.1038/jp.2008.189. Epub 2008 Nov 20.
citation: Gay AN, Lazar DA, Stoll B, Naik-Mathuria B, Mushin OP, Rodriguez MA, Burrin DG, Olutoye OO. Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets. J Pediatr Surg. 2011 Jun;46(6):1034-40. doi: 10.1016/j.jpedsurg.2011.03.025.
citation: Cortez J, Gupta M, Amaram A, Pizzino J, Sawhney M, Sood BG. Noninvasive evaluation of splanchnic tissue oxygenation using near-infrared spectroscopy in preterm neonates. J Matern Fetal Neonatal Med. 2011 Apr;24(4):574-82. doi: 10.3109/14767058.2010.511335. Epub 2010 Sep 9.