Clinical trial NCT05824377: To Determine the Best Feeding Practice in Preterm Infants on Non-invasive Ventilation.
Official title: To Determine the Best Feeding Practice in Preterm Infants on Non-invasive Ventilation.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prematurity; Extreme
Feeding Patterns
Ventilator Lung; Newborn
Keywords: Preterm infants
Feeding methods
bolus feeds
continuous feeds
non-invasive ventilation
RAM cannula
Lead sponsor: Cook County Health
Sponsor class: OTHER_GOV
First posted: 2023-04-21
Enrollment: 46
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Infants will be randomized into 2 groups; one will receive continuous nasogastric feeding and the other group will receive intermittent bolus feeds.

Each group will be stratified as per weight, thus (\<1000 g, 1000-1500 g, and \> 1500 g). It will be 1-1 randomization and will be randomized into each group by pulling a sealed envelope. Protected Health Information (PHI) will be de-identified by assigning a study code.

Sample size: A sample size of at least 23 in each arm was calculated using the SAS system. A power of 80% and a mean difference of 40% decrease in the length of time to achieve full feeds; and an SD of 8.5 was considered while calculating the number of patients. The mean length of time to achieve full feeds in our NICU as per chart review was 17 +/- 8.5 days.
Primary purpose: OTHER

Brief summary: To evaluate the duration to reach full feeds by comparing continuous gavage feeds versus bolus feeds in preterm infants who are on non-invasive respiratory support (RAM cannula - short binasal prongs).

Detailed description: Methods:

The study will be a randomized control trial at our NICU (Neonatal Intensive Care Unit) (Level III). Preterm infants on non -invasive ventilation (nasal intermittent positive pressure ventilation (NIPPV)/ continuous positive airway pressure (CPAP)) will be randomly assigned into either continuous feeds or bolus feeds groups. Baby will be fed enterally through a nasogastric tube via continuous or bolus feeds using either maternal milk or formula, according to parental choice. Feeds will be advanced as per the feeding guidelines or per treating physician. Currently we use both bolus and continuous feeding practice in our NICU, as per physician's discretion.

Intervention:

Infants will be randomized into 2 groups; one will receive continuous nasogastric feeding and the other group will receive intermittent bolus feeds. Continuous feeds will be delivered via an indwelling nasogastric/orogastric tube with a continuous infusion pump. Intermittent bolus feedings will be given by gravity every 3 hours over 15- 30 minutes.

Parents' consent will be taken when the infant is qualified for the study. The consent will be taken by one of the coinvestigators. Each coinvestigator will be trained to consent for standardization. Non-English-speaking parents will be consented using the medical video interpreter (Voyce). Accent will not be obtained as neonates aren't mature to give accent.

Patients will be randomized into each group by pulling a sealed envelope.

Monitoring for complications:

During the study, infants will be monitored for any complications due to either feeding protocol like feeding intolerance, reflux, abdominal distension, poor weight gain, any risk of aspiration pneumonia or necrotizing enterocolitis (NEC). Such symptoms are usually monitored by our NICU team as per our guidelines. These feeding issues can be encountered in either group. If such problems are encountered, feeding protocol will be changed as per the physician's clinical decision. Parents will be informed of the changes. Intention to treat protocol will be used while calculating the statistical analysis.

Guidelines for withholding the feeds (bolus or intermittent) or changing either group will be:

1. Excessive gastric residual (\> 50% of the volume fed)
2. Increase in abdominal girth (\>1.5-2.5 cm along with other signs and symptoms of intolerance to feeds)
3. Poor/slow weight gain (rate of weight gain is significantly below that expected for age and sex, or if weight has dropped ≥2 major percentile lines)
4. Occult blood positive in stools/visible blood in the stools
5. Concerns for neonatal sepsis clinically as per attending's discretion
6. Apnea pertaining for more than 20 secs alone or apnea for \> 10 seconds along with bradycardia (\<80) or desaturations (hypoxemia as per gestational age); and occurring more than 2 or 3 times a day and requiring intervention
7. Abnormal Abdominal X rays concerning for suspected NEC or NEC as per Bell's criteria
8. Infants who need to be on invasive ventilation
9. Treating physician's clinical decision

Feeding protocol:

BW: 500 -1000 grams:

Initiate: When baby is stable. Start with trophic feeds, that is, 5 -10 ml/kg/day.

Advance: If tolerating trophic feeds for 2-3 days, advance feeds by 10 ml/kg/day.

Initial choice of milk: Breast Milk/Donor Breast Milk / Formula (Enfamil) - 20Kcal/Oz.

Fortify: When 60-80 ml/kg/day feeds are reached, fortify to 22Kcal/Oz and within next few days to 24 Kcal/Oz.

BW 1000 - 1500 grams:

Initiate: When baby is stable. Trophic feeds 5-10 ml/kg/day. Advance: 15-20 ml/kg/day Initial choice of milk, fortifying and full feeds as above.

BW 1500 grams and above:

Initiate: 30 ml/kg/day. Advance: 20 -35 ml/kg/day Initial choice of milk, fortifying and full feeds as above.

Eligibility criteria: Inclusion Criteria:

1. Preterm Infants 24- 34 weeks of gestation
2. On Non-invasive ventilation (NIPPV/CPAP/HFNC)
3. Nothing by mouth (NPO) or on trophic feeds (\<20 ml/kg/day) at the time of randomization.

Exclusion Criteria:

1. Gestational Age \> 34 weeks
2. Infants on invasive ventilation or low flow nasal cannula and on feeding volume more than trophic feeds.
3. Major congenital anomalies.

Primary outcomes:
measure: Day of life to reach full feeds
timeFrame: From the date of randomization until the date of NICU discharge/death, assessed up to 1 year.
Secondary outcomes:
measure: Feeding interruptions
timeFrame: From the date of randomization until the date of NICU discharge/death, assessed up to 1 year.
measure: Time to reach (day of life) first oral feed
timeFrame: From the date of randomization until the date of NICU discharge/death, assessed up to 1 year.
measure: Weight gain, head circumference (HC) and Length.
timeFrame: From the date of randomization until the date of NICU discharge/death, assessed up to 1 year.
measure: Length of hospital stay
timeFrame: From the date of randomization until the date of NICU discharge/death, assessed up to 1 year.
measure: Use of investigative medicine for feeding intolerance
timeFrame: From the date of randomization until the date of NICU discharge/death, assessed up to 1 year.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Cook County Helath
state: Illinois
Study officials:
affiliation: Cook County Health
name: Rajeev Kumar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cresi F, Maggiora E, Borgione SM, Spada E, Coscia A, Bertino E, Meneghin F, Corvaglia LT, Ventura ML, Lista G; ENTARES Study Research Group. Enteral Nutrition Tolerance And REspiratory Support (ENTARES) Study in preterm infants: study protocol for a randomized controlled trial. Trials. 2019 Jan 18;20(1):67. doi: 10.1186/s13063-018-3119-0.
citation: Wang Y, Zhu W, Luo BR. Continuous feeding versus intermittent bolus feeding for premature infants with low birth weight: a meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2020 May;74(5):775-783. doi: 10.1038/s41430-019-0522-x. Epub 2019 Oct 28.
citation: Mukerji A, Abdul Wahab MG, Razak A, Rempel E, Patel W, Mondal T, Beck J. High CPAP vs. NIPPV in preterm neonates - A physiological cross-over study. J Perinatol. 2021 Jul;41(7):1690-1696. doi: 10.1038/s41372-021-01122-6. Epub 2021 Jun 5.
citation: Premji SS, Chessell L. Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature infants less than 1500 grams. Cochrane Database Syst Rev. 2011 Nov 9;2011(11):CD001819. doi: 10.1002/14651858.CD001819.pub2.
citation: Dumpa V, Kamity R, Ferrara L, Akerman M, Hanna N. The effects of oral feeding while on nasal continuous positive airway pressure (NCPAP) in preterm infants. J Perinatol. 2020 Jun;40(6):909-915. doi: 10.1038/s41372-020-0632-2. Epub 2020 Feb 21.
citation: Akintorin SM, Kamat M, Pildes RS, Kling P, Andes S, Hill J, Pyati S. A prospective randomized trial of feeding methods in very low birth weight infants. Pediatrics. 1997 Oct;100(4):E4. doi: 10.1542/peds.100.4.e4.