Trophic Feeding for Sepsis Prevention

(LET-FEED Trial)

Recruiting at 5 trial locations

Overseen By Ariel Salas, MD, MSPH

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Washington

Disqualifiers: Low birth weight, Congenital anomalies, Genetic conditions, Vasopressor use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if starting small feedings earlier can reduce the risk of infections in very premature infants without causing other problems. It compares two feeding approaches: starting enteral feeds (feeding through a tube) after 24 hours (Extended Trophic Feeds) versus after 72 hours (Limited Trophic Feeds). Babies born between 25 and almost 32 weeks, weighing less than 1500 grams, and without certain health issues may be eligible to participate. The trial will assess whether different feeding times affect infections and other health outcomes during the hospital stay. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in neonatal care.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. It focuses on feeding regimens for preterm infants, so it's best to consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that giving small amounts of nutrition, known as trophic feeding, is generally safe for premature babies. Both short-term and long-term trophic feeding are well-tolerated by very premature infants. Studies have found fewer cases of serious infections among those receiving trophic feeding. Importantly, death rates were the same in both groups, suggesting that both feeding methods are equally safe.

Additionally, research indicates no significant harmful effects from starting trophic feeding early for these infants. Advancing feeding more quickly has been linked to better outcomes, especially in babies born after 29 weeks and weighing more than 1000 grams. Overall, both short-term and long-term trophic feeding appear safe and do not increase the risk of major complications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these feeding protocols because they explore how different durations of trophic feeding can prevent sepsis in vulnerable newborns. Unlike traditional feeding strategies that might not focus as intensively on gradual advancements, these methods emphasize a careful, step-by-step increase in enteral feeds, either after one or three days of initial trophic feeding. By utilizing either the parent's own milk or donor human milk, these approaches aim to determine the optimal feeding strategy to support the immune system and reduce sepsis risk in infants. This trial could lead to more precise feeding guidelines that enhance health outcomes for newborns.

What evidence suggests that this trial's treatments could be effective for preventing late-onset sepsis in preterm infants?

This trial will compare two approaches to trophic feeding for preterm infants: Limited Trophic Feeds and Extended Trophic Feeding. Research has shown that tube feeding preterm infants can lower the risk of serious infections like sepsis by ensuring adequate nutrition. Some studies suggest that starting nutritional support early might also reduce infections such as pneumonia. Infants receiving small, gradual feedings benefit from better feeding tolerance, improved weight gain, and a lower risk of widespread infections. Both short-term and long-term feeding plans aim to provide the right nutrition to support growth and health. The overall goal is to deliver the right amount of nutrition at the right time to help these infants grow and fight infections. ^{1 2 3 5 6}

Who Is on the Research Team?

Gregory C Valentine

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

The LET-FEED trial is for very preterm infants born between 25 and almost 32 weeks, weighing less than 1500 grams. It's not for those with severe congenital issues affecting feeding or growth, extremely low birth weight, early vasopressor need, or terminal illness where life support is limited.

Inclusion Criteria

My birth weight was less than 1500 grams.

I was born between 25 and 31 weeks of pregnancy.

Consent to feed donor milk when parent's own milk is not available or of insufficient quantity

Exclusion Criteria

My baby needed medicine to raise blood pressure within 24 hours of birth.

Parent or legal guardian unable to provide consent within 36 hours after birth

I have a birth defect that affects how I am fed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 days

Treatment

Infants receive either limited trophic feeds for 24-36 hours or extended trophic feeds for 72-84 hours before advancing to full enteral feeds

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for late-onset sepsis and other secondary outcomes

Until hospital discharge, average of 40 weeks' gestation

Long-term Follow-up

Monitoring of growth metrics and other health outcomes until 36 weeks corrected gestational age

From birth to 36 weeks corrected gestational age

What Are the Treatments Tested in This Trial?

Interventions

• Extended Trophic Feeds
• Limited Trophic Feeds

Trial Overview This study tests if starting regular feeds after one day (limited trophic feeds) versus three days (extended trophic feeds) affects the risk of late-onset sepsis in very preterm infants without increasing other risks. Infants will be randomly assigned to either group.

How Is the Trial Designed?

Group I: Limited Trophic Feeds Experimental Treatment 1 Intervention

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.

Group II: Extended Trophic Feeding Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

University of Oklahoma

Collaborator

Trials

484

Recruited

95,900+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

University of South Florida

Collaborator

Trials

433

Recruited

198,000+

St. Joseph's Medical Center

Collaborator

Trials

1

Recruited

350+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10599301/

The Practice of Enteral Nutrition: Clinical Evidence for Feeding ... Enteral nutrition effectively prevents cumulative nutritional deficits in critically ill preterm infants, which may mitigate the risk of late-onset sepsis.

2. withpower.com withpower.com/trial/phase-3-length-of-stay-3-2025-03d85

Trophic Feeding for Sepsis Prevention (LET-FEED Trial) Some studies suggest that starting nutritional support early in critically ill patients, like those with sepsis, may help reduce infections such as pneumonia.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0002916522028155

Early progressive feeding in extremely preterm infants This trial confirms the results of our retrospective study that compared short with extended periods of trophic feeding in 192 extremely preterm infants (1).

4. eoeneonatalpccsicnetwork.nhs.uk eoeneonatalpccsicnetwork.nhs.uk/wp-content/uploads/2021/10/Enteral-Feeding-guideline.pdf

Enteral Feeding of Preterm Infants on the Neonatal Unit. Commence feeding as close to birth as possible. Initiate trophic feeds as soon as possible and maintain only as long as clinically indicated. Infants can ...

5. karger.com karger.com/neo/article/112/3/211/231625/Short-versus-Extended-Duration-of-Trophic-Feeding

Short versus Extended Duration of Trophic Feeding to ... These potential benefits include reduced duration of parenteral nutrition [8], reduced need for central access, reduced risk of serious ...

6. chop.edu chop.edu/sites/default/files/2025-01/5-Preterm-Nutrition-Consensus-Enteral-Feeds_Rev12-13-24.pdf

Title: Preterm Nutrition Consensus Enteral Feeds - The available trial data do not provide evidence of important beneficial or harmful effects of early trophic feeding for very preterm or very low birth weight ...