Limited Versus Extended Trophic Feeding (LET-FEED) Trial

NCT06893939 | Recruiting Phase 3 DMC

• 1 other identifier: STUDY00021132
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 6

Brief Summary

Study Hypothesis/Question In infants born very preterm, advancing enteral feeds after 24 hours from birth (limited trophic feeds) versus after 72 hours (extended trophic feeds) reduces the risk of all-cause late onset sepsis (LOS) without increasing the risk of other adverse outcomes. Study Design Type This is a multi-center, open-label, parallel-group, individual randomized controlled trial comparing two different trophic feeding regimens in preterm infants born between 25w0d and 31w6d. These infants will be randomly assigned to either the intervention group, receiving limited trophic feeding (20 to 25 mL/kg/day for one day) or the control group, receiving extended trophic feeding (20 to 25 mL/kg/day for three days) prior to advancing enteral feeds until full feeding volume (140 mL/kg/day) is achieved. Eligibility Criteria Preterm infants with gestational ages between 25 0/7 and 31 6/7 weeks and a birthweight of \<1500 grams who are admitted to six participating neonatal units will be eligible for inclusion. Infants with \<5th percentile for weight at birth, vasopressor use within first 24 hours of life major congenital/genetic anomalies affecting enteral feeding, growth, or mortality, and those with a terminal illness in which decisions to withhold or limit support have been made will be excluded. Infants of parents or legal guardians who are unable to provide consent within 36 hours of birth will also be excluded. Study Intervention/Methods Written parental informed consent will be obtained prenatally or within the first 36 hours of birth. Infants will be randomized to receive limited trophic feeds of 24 to 36 hours or extended trophic feeds for 72 hours prior to the advancement of enteral feeds. Infants will be fed parent's own milk (POM) with donor human milk as the alternative if POM is unavailable. Primary Outcome Late-onset sepsis, defined as positive blood, urine, and/or cerebrospinal fluid (CSF) cultures in the presence of compatible clinical signs of sepsis, occurring after postnatal day 3 and before hospital discharge, and treated with antibiotics for 5 days or more. Secondary Outcome(s) The trial will assess various secondary outcomes including length of hospital stay, all-cause in-hospital mortality, duration of IV fluids and central line utilization, necrotizing enterocolitis (Bell's stage IIa or higher), severe intraventricular hemorrhage (grade III or IV either unilaterally or bilaterally), bronchopulmonary dysplasia (oxygen requirement or positive pressure ventilation at 36 weeks corrected gestational age), or retinopathy of prematurity requiring intervention. Additionally, growth metrics throughout hospitalization will be evaluated using change in weight, length, and head circumference z-scores from birth to 36 weeks' corrected gestational age between infants in the limited and extended trophic feeding groups.

Conditions

Sepsis; Length of Stay; Mortality

Keywords

Feeding; Nutrition; Prematurity; Very preterm; Trophic; Trophic feeds; Trophic feeding; enteral feeds; sepsis

Outcome Measures

Primary Outcomes (1)

• Late Onset Sepsis

  Defining LOS: For the purposes of this study, a positive finding of LOS will be defined as the following: a body fluid culture (e.g. blood, urine, CSF) that returns positive, obtained in the presence of compatible clinical signs of sepsis (e.g. hypotension, apnea/bradycardia, increasing oxygen requirements, increasing metabolic acidosis, lactic acidosis, hypoglycemia, hyperglycemia, etc.) occurring after 72 hours from birth and before hospital discharge that was treated with antibiotics for a minimum of 5 days.

  Through study completion, the end of NICU hospitalization, an average of 40 weeks' gestation

Secondary Outcomes (17)

• All-Cause In-Hospital Mortality

  Through study completion, the end of NICU hospitalization, an average of 40 weeks' gestation

• Duration of parenteral nutrition

  Through study completion, the end of NICU hospitalization, an average of 40 weeks' gestation

• Duration of Central Venous Access

  Through study completion, the end of NICU hospitalization, an average of 40 weeks' gestation

• Length of hospitalization

  Through study completion, the end of NICU hospitalization, an average of 40 weeks' gestation

• Time to reach full enteral feeding volumes

  Through study completion, the end of NICU hospitalization, an average of 40 weeks' gestation

Study Arms (2)

Extended Trophic Feeding

ACTIVE COMPARATOR

Advancing enteral feeds after 3 days of trophic feeds of 20-25 mL/kg birthweight/day. Advancement of enteral feeds will be by approximately 30 mL/kg birthweight/day after 3 days of trophic feeds. Advancement will occur until achieving at least 140 mL/kg birthweight/day of enteral feeds. Enteral feeds will consist of parent's own milk or donor human milk.

Other: Extended Trophic Feeds (3 days of trophics)

Limited Trophic Feeds

EXPERIMENTAL

Advancing enteral feeds after 1 day of trophic feeds of 20-25 mL/kg birthweight/day. Advancement of enteral feeds will be by approximately 30 mL/kg birthweight/day until achieving at least 140 mL/kg birthweight/day of enteral feeds. Enteral feeds will consist of parent's own milk or donor human milk.

Other: Limited Trophic Feeds (1 day of trophic feeds)

Interventions

Limited Trophic Feeds (1 day of trophic feeds) OTHER

Advancing enteral feeds after 1 day of trophic feeds of 20-25 mL/kg birthweight/day. Advancement of enteral feeds will be by approximately 30 mL/kg birthweight/day until achieving at least 140 mL/kg birthweight/day of enteral feeds. Enteral feeds will consist of parent's own milk or donor human milk.

Also known as: Limited Trophic Feeds

Limited Trophic Feeds

Extended Trophic Feeds (3 days of trophics) OTHER

Advancing enteral feeds after 3 days of trophic feeds of 20-25 mL/kg birthweight/day. Advancement of enteral feeds will be by approximately 30 mL/kg birthweight/day after 3 days of trophic feeds. Advancement will occur until achieving at least 140 mL/kg birthweight/day of enteral feeds. Enteral feeds will consist of parent's own milk or donor human milk.

Extended Trophic Feeding

Eligibility Criteria

• Age: 0 Hours - 36 Hours
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• \<1500 gram birthweight
• w0d-31w6d at birth
• Consent to feed donor milk when parent's own milk is not available or of insufficient quantity

You may not qualify if:

• \<5th percentile for weight at birth (Fenton growth curve)
• Parent or legal guardian unable to provide consent within 36 hours after birth
• Congenital anomaly affecting decisions on enteral feedings (e.g. gastroschisis, omphalocele, congenital diaphragmatic hernia, congenital heart disease, etc.)
• Known genetic condition affecting growth, feeding, or mortality
• Vasopressor use within first 24 hours after birth (not including hydrocortisone)
• Considered terminally ill

Sponsors & Collaborators

• University of Washington: lead
• University of Alabama at Birmingham: collaborator
• Baylor College of Medicine: collaborator
• University of South Florida: collaborator
• University of Oklahoma: collaborator
• St. Joseph's Medical Center: collaborator

Study Sites (6)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

NOT YET RECRUITING

University of South Florida

Tampa, Florida, 33606, United States

NOT YET RECRUITING

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

NOT YET RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

NOT YET RECRUITING

University of Washington

Seattle, Washington, 98195, United States

NOT YET RECRUITING

St. Joseph's Medical Center

Tacoma, Washington, 98405, United States

RECRUITING

Related Publications (32)

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MeSH Terms

Conditions

Sepsis; Premature Birth

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Gregory C Valentine

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gregory C Valentine, MD MED FAAP

CONTACT

(206) 543-3200; gcvalent@uw.edu

Ariel Salas, MD, MSPH

CONTACT

asalas@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This will be an open label trial as it relates to do different feeding approaches preventing masking/blinding.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Pediatrics

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 25, 2025
• Study Start: July 3, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Deidentified data will be shared with researchers requesting access to the data if they have a scientifically sound and reasonable plan. The data will be shared within 6-12 months of receiving the request by the researchers and a determination is made.
• Access Criteria: Deidentified data will be shared with researchers requesting access to the data if they have a scientifically sound and reasonable plan. The data will be shared within 6-12 months of receiving the request by the researchers and a determination is made. The data will be transferred via a HIPAA secure format.

Locations

US (6)