Randomized Controlled Crossover Trial of Postpyloric Feedings to Improve Pulmonary Outcomes in High-risk Preterm Infants

A Randomized Controlled Crossover Trial of Postpyloric Versus Gastric Feedings to Improve Pulmonary Outcomes in High-risk Preterm Infants

The purpose of this study is to determine if postpyloric feedings effectively improve objective measures of pulmonary health in preterm infants with chronic lung disease when compared with nasogastric (NG) feedings. This research will (1) determine the optimal nutritional management to prevent a common and costly complication of prematurity, and (2) use a novel crossover design that examines outcomes of clinical endpoints alongside biomarkers.

Study Overview

• Status: Not yet recruiting
• Conditions: Bronchopulmonary Dysplasia
• Intervention / Treatment: Procedure: Gastric Feeds; Procedure: Jejunal Feeds

Detailed Description

Bronchopulmonary dysplasia (BPD) affects up to 50,000 preterm infants annually in the United States and is the most common complication of prematurity. Despite improving survival in preterm infants, incidence of BPD is increasing. Overall, 11% of infants are born preterm in the United States annually. While many outcomes of prematurity, including survival, have improved over time, the incidence of BPD has increased.

Nearly all babies with BPD require provision of feeds via an enteral tube due to feeding immaturity and ongoing need for respiratory support, and up to ¼ of babies with the most severe forms of BPD require this long-term, and are discharged home with nasal or surgically placed feeding tubes. However, enteral feeding into the stomach frequently results in reflux in preterm infants. This may cause aspiration into the respiratory tract, which can result in further damage to the lungs and worsen respiratory outcomes.

The study will measure the impact of NJ feedings on lung disease severity in a prospective crossover trial among infants at high-risk of developing BPD.

Each randomized patient will participate in two blocks of feeding, a nasogastric (NG) and a nasojejunal (NJ, postpyloric) block. Subjects will be randomized to either the control (NG) or intervention (NJ) feedings in the first block. Outcomes will be compared pairwise by subject between the NG and NJ blocks.

The findings of this study would be immediately impactful for neonatologists, pediatricians, pediatric pulmonologists, pediatric gastroenterologists, advanced practitioners, and nutritionists who determine nutritional strategies for preterm infants.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jonathan Levin, MD; Phone Number: 617-355-1900; Email: jonathan.levin@childrens.harvard.edu
• Study Contact Backup: Name: Vanessa J Young, MS; Phone Number: 617-355-8330; Email: vanessa.young@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
      • Contact: Jonathan Levin, MD; Phone Number: 617-335-1900; Email: jonathan.levin@childrens.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Preterm infants born < 32 weeks' gestation may enroll at 34-44 weeks post-menstrual age, who:

1. Remain on either invasive ventilation or non-invasive ventilation (continuous positive airway pressure or nasal intermittent positive pressure ventilation) for minimum 48 hours at the time of study entry. The minimum support required for inclusion is CPAP > 5cm H2O or CPAP 5 with FiO2 > 21%.
2. Have ongoing need for respiratory support due to underlying lung disease from prematurity.
3. Are tolerating > 80 ml/kg/day of enteral feedings at baseline, either via nasogastric (NG) or nasojejunal (NJ) tube. Patients may be receiving gastric (NG) or postpyloric (NJ) feedings.

Exclusion Criteria:

1. Infants who are transiently on respiratory support at the time of study entry due to another reason than underlying lung disease from prematurity; for example, recovery from a surgical intervention.
2. Infants who have other comorbidities that significantly contribute to lung disease, including cyanotic congenital heart disease, or other genetic, congenital, or pulmonary abnormalities.
3. Infants who were evaluated for necrotizing enterocolitis (including holding feedings) in the 7 days prior to study enrollment.
4. Infants with known gastrointestinal or airway malformations that would affect tolerance of feeds or the route of delivery of enteral feedings.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Gastric Followed by Jejunal Feeds; Participants randomized into this group will begin with one ten-day block of nasogastric (NG) feeds followed by one ten-day block of nasojejunal (NJ, postpyloric) feeds.	Procedure: Gastric Feeds; The participant will receive nutrition via a nasogastric tube. Gastric feedings will be administered as bolus feeds every 3 hours over 1 hour. Infants who are deemed able to advance oral feedings via mouth during the study period will be permitted to do so, and this will be recorded.; Other Names: Nasogastric Feeding; NG feeds; Procedure: Jejunal Feeds; The participant will receive nutrition via a nasojejunal tube. Postpyloric feedings will be administered continuously into the jejunum. Infants who are deemed able to advance oral feedings via mouth during the study period will be permitted to do so, and this will be recorded.; Other Names: Nasojejunal Feeding; Postpyloric Feeding; NJ Feeds
Experimental: Group B: Jejunal Followed by Gastric Feeds; Participants randomized into this group will begin with one ten-day block of nasojejunal (NJ, postpyloric) feeds followed by one ten-day block of nasogastric (NG) feeds.	Procedure: Gastric Feeds; The participant will receive nutrition via a nasogastric tube. Gastric feedings will be administered as bolus feeds every 3 hours over 1 hour. Infants who are deemed able to advance oral feedings via mouth during the study period will be permitted to do so, and this will be recorded.; Other Names: Nasogastric Feeding; NG feeds; Procedure: Jejunal Feeds; The participant will receive nutrition via a nasojejunal tube. Postpyloric feedings will be administered continuously into the jejunum. Infants who are deemed able to advance oral feedings via mouth during the study period will be permitted to do so, and this will be recorded.; Other Names: Nasojejunal Feeding; Postpyloric Feeding; NJ Feeds

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in modified respiratory severity score (mRSS)	mRSS is a validated measurement for respiratory severity in chronic lung disease in neonates.	Over a 15 day period during study participation
Tracheal Aspirates	For infants who remain on invasive respiratory support, the study team will collect tracheal aspirates for the measurement of bile acid and pepsin concentration.	Over a 15 day period during study participation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Support Over the Course of the Study	The study team will monitor the patient's respiratory support needs by reviewing the medical record.	Over a 15 day period during study participation
Nutritional Status Over the Course of the Study	The study team will monitor the patient's nutritional status by reviewing the medical record at the end of each study period.	Over a 15 day period during study participation

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Jonathan Levin, MD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: February 9, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Actual): March 21, 2023

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: GERD; Bronchopulmonary Dysplasia; Chronic Lung Disease of Prematurity; Postpyloric Feeding; Nasojejunal Feeding; Gastro-esophageal Reflux
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia
• Other Study ID Numbers: IRB-P00043302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No