Duodenal Feeds in Very Low Birth Weight Infants

Study Overview
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Brief Summary
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Premature infants have high rates of bronchopulmonary dysplasia (BPD) due to prematurity of the participants' lungs and the need for prolonged respiratory support. These infants are at increased risk for gastroesophageal reflux and aspiration which may exacerbate lung injury. Transpyloric feeds, specifically duodenal feeds, may be used to bypass the stomach and directly feed the duodenum decreasing the amount of gastric reflux contributing to aspiration. Duodenal feeds are equivalent to gastric feeds with regards to nutritional outcomes, and have been shown to decrease events of apnea and bradycardia in premature infants. This study will evaluate the feasibility and safety of duodenal feeds in premature infants. The hypothesis is that duodenal feeds may be safely and successfully performed in premature very low birth weight infants.

Detailed Description
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The primary outcome of this study is the safety and feasibility of duodenal feeds in very low birth weight infants. The secondary outcomes are various measures related to growth, respiratory support, comorbidities, and hospitalization. Eligibility of infants admitted to the Johns Hopkins All Children's Neonatal Intensive Care Unit (NICU) will be determined based on inclusion and exclusion criteria. Eligible infants will be recruited and enrolled by 14 days of life after informed consent is obtained. Randomization of the infants into two groups- investigational continuous Duodenal Feeds (DF) or standard Gastric Feeds (GF) - will occur just prior to the infants advancing beyond 50mL/kg/day of enteral feeds. All enrolled infants will be fed per the institutional feeding protocol. Once infants advance past 50mL/kg/day of enteral feeds, at this point infants will be randomized to DF or GF groups in a 1:1 block randomization using blinded envelopes. Multiple gestation infants will be randomized individually. Placement of gastric tubes will be per standard of practice, and insertion of duodenal tube will be per manual of operations. Continuous duodenal feeds will be provided over 24 hours as a continuous infusion through a nasoduodenal or oro-duodenal tube. Standard gastric feeds will be infused via a nasogastric or orogastric tube per the instructions of the medical team. Gastric feeds are provided as standard of care in the NICU; intermittent bolus feeds over 15-60 minutes. Feeding time may be prolonged by the medical team, for longer than 60 minutes and possibly even be given continuously, for various reasons (emesis, reflux, apnea, bradycardia, etc.) and will be monitored and recorded. Feed volume and advancement will continue to be determined by standardized institutional feeding guidelines. Decision to provide further fortification of feeds beyond institutional guidelines will be determined by the medical team and not standardized in this protocol. Once full enteral feeds are achieved (total fluid goal of at least 140mL/kg/day), patients will continue to receive feeds via the designated route. An institutional Infant Driven Feeding Guideline is utilized to evaluate readiness to orally feed and to transition premature infants from enteral to oral feeds. Once an infant is eligible to receive oral feeds per this guideline (32 weeks postmenstrual age, and tolerating ≤2L flow via nasal cannula for at least 24 hours), the study will allow the medical team to transition infants in the DF group to gastric feeds. Regarding transitioning infant from duodenal to gastric feeds, infants are initially placed on continuous gastric feeds, and once the participants have demonstrated tolerance (no evidence of reflux, increased respiratory support, emesis), the participants are then transitioned to bolus gastric feeds progressively. Infants may be allowed to orally feed during this transition period if the participants meet the appropriate infant driven feeding scores per protocol. All infants in this study will be monitored for primary and secondary outcomes through the duration of admission and up until the time of discharge. Safety events will be frequently monitored for throughout the duration of admission and addressed immediately if warranted.

Official Title
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Feasibility and Safety of Duodenal Feeds in Very Low Birth Weight Infants

Conditions
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BPD - Bronchopulmonary Dysplasia, VLBW - Very Low Birth Weight Infant, Feeding Disorder Neonatal, Feeding; Difficult, Newborn, Premature Birth, Chronic Lung Disease of Prematurity

Intervention / Treatment
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* Other: Mode of Delivery of Feeds


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants admitted to the Johns Hopkins All Children's NICU before 72 hours of life Infants with a birth weight <1251g Exclusion Criteria: First obtained pH <7.0 APGAR <5 at 5 minutes (The Apgar score is a test given to newborns soon after birth. This test checks a baby's heart rate, muscle tone, and other signs to see if extra medical care or emergency care is needed. Appearance, Pulse, Grimace, Activity, Respiration (APGAR)) Infants on hydrocortisone for hypotension prior to randomization Infants with intrauterine growth restriction (IUGR) defined by birth weight ≤10th percentile for gestational age Infants with congenital anomalies, including but not limited to: Chromosomal abnormalities;Structural airway or pulmonary abnormalities (e.g. tracheoesophageal fistulas, cleft palate, congenital pulmonary adenomatous malformation, etc.); Abdominal anomalies requiring surgical interventions (e.g. intestinal atresia, intestinal webs, gastroschisis, omphalocele, anal atresia); Major cardiac anomalies Infants with a history of intestinal perforation or NEC Presence of gastrostomy tube Infants who have not been initiated on any volume of enteral feeds by 10 days of life

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Gastric Feeds<br>Patients in this arm will receive feeds via the standard route which is gastric feeds. | |
| Experimental: Duodenal Feeds<br>Patients in this arm will receive feeds via the experimental route which is duodenal feeds. | Other: Mode of Delivery of Feeds<br>* Eligible infants will be recruited and enrolled and randomized to either duodenal feeds (DF) or gastric feeds (GF), which will occur just prior to the infants advancing beyond 50mL/kg/day of enteral feeds. All enrolled infants will be fed per our institutional feeding protocol. Once infants advance past a volume of 50mL/kg/day of enteral feeds, at this point infants will be randomized to DF or GF groups.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of successful placements of duodenal tubes | Success to be measured by appropriate placement of the duodenal tube within the duodenum as confirmed by radiographic imaging. | 12 months | 
| Safety as assessed by number of intestinal perforations | Safety of duodenal feeds in very low birth weight infants as measured by the number of intestinal perforations secondary to placement of duodenal tube. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Supplemental oxygen requirement | Number of days on supplemental oxygen >21% throughout duration of hospitalization | duration of hospitalization, up to 15 months | 
| Number of participants with Bronchopulmonary Dysplasia | Mild, moderate, severe Bronchopulmonary Dysplasia (BPD) as defined by the NICHD/NHLBI/ORD Workshop published in 2001 | 15 months | 
| Number of deaths during hospitalization |  | 15 months | 
| Number of days of mechanical ventilation | Days of invasive mechanical ventilation up until hospital discharge | 15 months | 
| Number of participants with late-onset sepsis | Number of participants diagnosed with Culture-positive sepsis after 72 hours of life | 15 months | 
| Central line days | Cumulative days of indwelling central venous catheters (peripherally inserted central catheters, tunneled venous catheters, umbilical venous catheters) | 15 months | 
| Number of participants with necrotizing enterocolitis | Number of participants with necrotizing enterocolitis (NEC) defined by Modified Bells Stage II or greater | 15 months | 
| Number of replaced enteral tubes | Number of replaced enteral tubes, gastric or duodenal, per patient | 15 months | 
| Number of Radiographs related to enteral tube placement | Number of radiographs obtained with the indication of enteral tube placement, gastric or duodenal | 15 months | 
| Weight percentile at 36 weeks postmenstrual age | Weight percentile at 36 weeks postmenstrual age | At 36 weeks | 
| Height percentile at 36 weeks postmenstrual age | Height percentile at 36 weeks postmenstrual age | At 36 weeks | 
| Head circumference percentile at 36 weeks postmenstrual age | Head circumference percentile at 36 weeks postmenstrual age | At 36 weeks | 
| Z-scores for weight at 36 weeks postmenstrual age | Z-scores for weight at 36 weeks postmenstrual age calculated using PediTools | At 36 weeks | 
| Z-scores for height at 36 weeks postmenstrual age | Z-scores for height at 36 weeks postmenstrual age calculated using PediTools | At 36 weeks | 
| Z-scores for head circumference at 36 weeks postmenstrual age | Z-scores for head circumference at 36 weeks postmenstrual age calculated using PediTools | At 36 weeks | 
| Daily daily weight gain | Average daily weight gain (kg/day) calculated from birth until 36 weeks postmenstrual age using the fetal-infant growth reference (FIGR) equation | At 36 weeks | 
| Length of stay | Length of hospital stay (days) | duration of hospitalization, up to 15 months | 
| Need for excess fortification of feeds | Number of participants requiring fortification beyond 24kcal/oz | 15 months | 
| Use of postnatal dexamethasone | Number of participants requiring use of postnatal dexamethasone for respiratory indications | 15 months | 
| Use of chronic diuretics | Number of participants requiring use of chronic diuretics including thiazide diuretics and spironolactone | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duodenal feeds, Transpyloric feeds, Bronchopulmonary Dysplasia, BPD, Premature infant, Neonate