Chronic Lung Disease of PrematurityCONFERNCT03961139
Continuous Versus Intermittent Bolus Feeding in Very Preterm Infants - Effect on Respiratory Morbidity
A study testing Method of feeding; continuous feeding OR bolus feeding in people with Chronic Lung Disease of Prematurity and Bronchopulmonary Dysplasia, run by National University Hospital, Singapore at 2 sites in 2 countries.
Trial summary
Chronic Lung Disease (CLD) of Prematurity is a common yet challenging co-morbidity affecting extremely premature newborns. Multifactorial influences leading to this co-morbidity is known and targeted in various research studies. Gastroesophageal reflux (GER) is common among the same cohort of patients. Read more about this study
- Who is it for?
- Ages 1 day to 3 days
- Conditions the study is for
- Chronic Lung Disease of Prematurity, Bronchopulmonary Dysplasia
- What is being tested?
- Method of feeding; continuous feeding OR bolus feeding
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 3 Dec 2019to Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 3 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants with a birth weight <1250g and a gestational age of between 24+0 - 33+6 weeks
Who cannot join
- Major congenital malformation
- Chromosomal abnormality
- 10-minute Apgar score of =3
- Not expected to survive beyond 72 hours of age
- Bilateral grade 4 intraventricular haemorrhage (IVH)
- Did not consent / Consent not available
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Malaysia1 site, 1 recruiting
- Recruiting
NICU, Universiti Kebangsaan Malaysia
Kuala Lumpur, 56000
Fook-Choe Cheah, FRCPCH, +60 3 91456637, cheahfc@ppukm.ukm.edu.my
Singapore1 site, 1 recruiting
- Recruiting
NICU, National University Hospital
Singapore, 119074
Agnihotri Biswas, MRCPCH, 67725075, biswas_agnihotri@nuhs.edu.sg
Jiun Lee, MRCPCH, 67725075, lee_jiun@nuhs.edu.sg
About this study
Official title: Continuous Versus Intermittent Bolus Feeding in Very Preterm Infants - Effects on Respiratory Morbidity: A Multicentre Randomised Controlled Clinical Trial
Chronic Lung Disease (CLD) of Prematurity is a common yet challenging co-morbidity affecting extremely premature newborns. Multifactorial influences leading to this co-morbidity is known and targeted in various research studies. Gastroesophageal reflux (GER) is common among the same cohort of patients. The investigators hypothesize that recurrent milk reflux into the airways of the premature babies worsen the inflammation of premature lungs and is a major contributor of CLD.
The investigators hypothesize that Continuous feeding (CF) minimises GER and micro-aspiration, thereby reducing the incidence and severity of CLD in high-risk infants.
Our aim is to compare the effect of intermittent bolus versus continuous intra-gastric feeding on the incidence and severity of CLD in very low birth weight infants ≤ 1250 grams.
Read the detailed description
The pathogenesis of bronchopulmonary dysplasia (BPD) is complex and multifactorial. As a result of premature birth, developmental arrest during a critical period of fetal lung development compounded by mechanical, oxidative and other injuries sustained during neonatal respiratory care forms the basis of pathogenesis. BPD affects up to 50% of infants with birth weight less than 1000 g. Between 2000 and 2009, despite advancement of neonatal care, annual BPD rates reported by Vermont Oxford Network among very low birth weight infants varied from 26.2% to 30.4% without any decline. Severely affected infants often require prolonged ventilation, high oxygen use, alternative airway and several potent medications over the first few months to years of their lives. High mortality rates, neurodevelopmental delay, respiratory morbidity and growth failure are associated with BPD.
Treatment of severe BPD with or without pulmonary hypertension is challenging. Prolonging the pregnancy in the face of premature labour, treating perinatal infections, augmenting pulmonary maturity with corticosteroids, judicious oxygen use, lung protective ventilation and optimizing nutrition to promote growth are important and well established measures to prevent or modify the progress of the chronic lung disease.
It is common to find infants with BPD also having significant symptoms of reflux. Gastroesophageal reflux (GER) is a well-known co-morbidity among preterms and ex-preterms on chronic ventilation, many of whom go on to require surgical fundoplication to stop the reflux thus preventing further lung damage. Some have reported dramatic respiratory improvement after resolution of GER. In the early days of a preterm baby with respiratory distress, GER is common and silent. Among infants, diagnosis of pathologic GER from a benign one is difficult. Many neonatal intensive care units (NICUs) would investigate for GER only when faced with moderate to severe BPD to achieve better respiratory symptom control. However GER has not been studied well as a factor precipitating the development of BPD among VLBW neonates. This is the focus of the study.
Aspiration of gastric contents into the lung is a widespread phenomenon in mechanically ventilated preterm infants. In animal models of gastric aspiration, gastric particulates altered the pulmonary mechanics, increased pulmonary inflammatory cells, released pro-inflammatory mediators, and inactivated surfactant. Development of bacterial pneumonia is a well-recognized complication following aspiration of gastric contents. The investigators hypothesize that repeated aspirations would aggravate and accelerate an inflammatory response in the lung finally leading on to BPD. In addition oxygen mediated damage and mechanical ventilation potentiate lung injury due to aspiration. Logically, if GER and aspiration could be minimized, it could decrease the incidence and severity of BPD.
Certain positioning of the baby, small volume of feed increment, keeping a close watch on feed tolerance are practical ways of improving feeding tolerance and reducing GER. The intermittent bolus intra-gastric feeding method is commonly used to feed premature babies. Other alternatives are continuous intra-gastric (feed volume is slowly infused in the stomach over couple of hours through the nasogastric tube) and continuous transpyloric feeding (feeding tube passes beyond the stomach to the duodenum and feed volume is slowly infused over hours). Transpyloric continuous feeding as compared to intermittent gastric bolus feeding, has been found to significantly reduce ventilatory support requirements in extremely low birth weight (ELBW) infants, possibly via its effect of minimising GER. In this study, none of the babies who received transpyloric feeding developed significant BPD and in addition babies with significant BPD improved after switching to transpyloric method. Transpyloric feeding tubes however are challenging to insert, and intestinal perforation is an uncommon but significant adverse effect. This feeding method is also not physiological as it bypasses the stomach. It remains to be seen if continuous gastric feeds, which is easily administered and safer, would yield some of the advantages of continuous transpyloric feeds over intermittent gastric feeding.
A Cochrane review in 2011 of continuous intra-gastric versus intermittent bolus intra-gastric feeding for premature infants found conflicting results, and was unable to make recommendations regarding the benefits and risks of these feeding methods. Clinical outcomes of interest from these trials were related to growth, feeding tolerance and gastrointestinal complications. The Cochrane review importantly found no significant difference in somatic growth and incidence of necrotising enterocolitis (NEC) between either feeding methods. Another Cochrane review in 2014 did not identify any randomised trial that evaluated the effects of continuous versus intermittent bolus intragastric tube feeding on gastro-oesophageal reflux disease in preterm and low birth weight infants and opined that well-designed and adequately powered trials are needed in this field. There were no studies comparing the effect of the above feeding methods on respiratory outcomes either.
Trial objectives
Aim: To compare the effect of intermittent bolus versus continuous intra-gastric feeding on the incidence and severity of BPD in very low birth weight infants (≤ 1250 grams).
Hypothesis: Continuous feeding (CF) minimises silent GER and micro-aspiration, thereby reducing the incidence and severity of bronchopulmonary dysplasia (BPD) in high-risk infants when compared to intermittent bolus feeding (BF).
Statistical considerations
Sample size calculation: based on 2015 data from the Singapore National Very-Low-Birth-Weight (VLBW) Infant Network for infants ≤ 1250 grams, mortality rate was 12.9% and BPD rate (defined as any oxygen supplementation or any respiratory support at 36 weeks post-conceptional age) was 29.4%. Thus the composite primary outcome rate was 42.3%. For a primary outcome rate reduction from 45% to 22.5%, with a type 1 error rate of 5% and a power of 80%, a sample size of 68 infants in each arm is required, giving a total sample size of 136 infants.
- Being tested
- Method of feeding; continuous feeding OR bolus feeding
- Keywords
- Prematurity, Randomised control trial (RCT), BPD, CLD, continuous feeding
- Medical subject headings
- Bronchopulmonary Dysplasia, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Method of feeding; continuous feeding OR bolus feedingOther
CF: Infants fed through a naso or orogastric tube in a continuous fashion using syringe pump. Each feed cycle is of 4 hours (3 hrs continuous feeding and 1 hour rest). 6 feed cycles in a day.
BF: Infants fed through a naso or orogastric tube in a gravity dependent bolus feeding every 2-3 hours. Each feed would take approximately 10 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Continuous feeding (CF) | Experimental | Infants fed through a naso or orogastric tube in a continuous fashion using syringe pump. Each feed cycle is of 4 hours (3 hrs continuous feeding and 1 hour rest). 6 feed cycles in a day.
Feed volume increment per day is as per departmental protocol and same as comparator arm. Receives: Other: Method of feeding; continuous feeding OR bolus feeding |
| Bolus feeding (BF) | Active comparator | Infants fed through a naso or orogastric tube in a gravity dependent bolus feeding every 2-3 hours. Each feed would take approximately 10 minutes.
Feed volume increment per day is as per departmental protocol and same as experimental arm. Receives: Other: Method of feeding; continuous feeding OR bolus feeding |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of BPD
BPD as defined by 2001 NICHD criteria
Measured: occurring before 36 weeks post menstrual age or 28 days of life
Incidence of Death
Death occurring before 36 weeks post menstrual age or 28 days of life
Measured: occurring before 36 weeks post menstrual age or 28 days of life
Secondary outcomes (7)
Invasive Ventilatory requirements
Days on invasive ventilation
Measured: 36 weeks post menstrual age or 28 days of life
Any Ventilatory requirements
Days on any ventilatory (invasive or non invasive) support
Measured: 36 weeks post menstrual age or 28 days of life
Supplemental Oxygen support
Days on supplemental oxygen
Measured: 36 weeks post menstrual age or 28 days of life
Feed tolerance
Time (days) from randomization to achievement of full feeds (defined as 150ml/Kg/Day)
Measured: 36 weeks post menstrual age or 28 days of life
Weight outcomes
Z-scores for weight (grams)
Measured: birth, 36 weeks and 40 weeks post menstrual age
Length outcomes
Z-scores for length (cm)
Measured: birth, 36 weeks and 40 weeks post menstrual age
Head Growth outcomes
Z-scores for head circumference (cm)
Measured: birth, 36 weeks and 40 weeks post menstrual age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2019
- Study start3 Dec 2019
- Primary completionJun 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for Chronic Lung Disease of PrematurityStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised-controlled trial with 2 parallel groups (1:1 ratio). Control group: intermittent bolus intra-gastric tube feeding (BF), Intervention group: continuous intra-gastric tube feeding (CF). Not blinded. Stratified randomization along following birth weight groups: 1. \</=750 g 2. 751 - 1000 g 3. 1001 -1250 g Method of randomisation: Computer generated randomization codes stored in sealed opaque envelopes. Intervention started by 72 hours of life (more than trophic feed volume achieved) and continued until an infant reaches a weight of 1.6 kg and is determined by the attending Neonatologist to be ready to commence oral feeding by breast or bottle, or when an infant attains a post-conceptional age of 36 weeks, whichever is earlier. Continuous fed is delivered through a nasogastric tube by a syringe pump over 3hrs with 1 hour of break - 6 cycles a day. Feed volume, type of feed, feed increment regulated by the clinical team. Intention to treat analysis.
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Agnihotri Biswas, MRCPCH, Principal investigator, Senior Consultant Neonatologist, NUH Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03961139
- Sponsor's protocol ID
- 2018/00773
- Other IDs
- 2018
- Acronym
- CONFER
- Status last verified
- May 2019
- First submitted
- 15 May 2019
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bancalari E, Claure N, Sosenko IR. Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol. 2003 Feb;8(1):63-71. doi: 10.1016/s1084-2756(02)00192-6.
PubMed 12667831Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, Hale EC, Newman NS, Schibler K, Carlo WA, Kennedy KA, Poindexter BB, Finer NN, Ehrenkranz RA, Duara S, Sanchez PJ, O'Shea TM, Goldberg RN, Van Meurs KP, Faix RG, Phelps DL, Frantz ID 3rd, Watterberg KL, Saha S, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010 Sep;126(3):443-56. doi: 10.1542/peds.2009-2959. Epub 2010 Aug 23.
PubMed 20732945Horbar JD, Carpenter JH, Badger GJ, Kenny MJ, Soll RF, Morrow KA, Buzas JS. Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009. Pediatrics. 2012 Jun;129(6):1019-26. doi: 10.1542/peds.2011-3028. Epub 2012 May 21.
PubMed 22614775Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, Wrage LA, Poole K; National Institutes of Child Health and Human Development Neonatal Research Network. Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics. 2005 Dec;116(6):1353-60. doi: 10.1542/peds.2005-0249.
PubMed 16322158Jobe AH. The new bronchopulmonary dysplasia. Curr Opin Pediatr. 2011 Apr;23(2):167-72. doi: 10.1097/MOP.0b013e3283423e6b.
PubMed 21169836Cristea AI, Carroll AE, Davis SD, Swigonski NL, Ackerman VL. Outcomes of children with severe bronchopulmonary dysplasia who were ventilator dependent at home. Pediatrics. 2013 Sep;132(3):e727-34. doi: 10.1542/peds.2012-2990. Epub 2013 Aug 5.
PubMed 23918888Walsh MC, Morris BH, Wrage LA, Vohr BR, Poole WK, Tyson JE, Wright LL, Ehrenkranz RA, Stoll BJ, Fanaroff AA; National Institutes of Child Health and Human Development Neonatal Research Network. Extremely low birthweight neonates with protracted ventilation: mortality and 18-month neurodevelopmental outcomes. J Pediatr. 2005 Jun;146(6):798-804. doi: 10.1016/j.jpeds.2005.01.047.
PubMed 15973322Khemani E, McElhinney DB, Rhein L, Andrade O, Lacro RV, Thomas KC, Mullen MP. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics. 2007 Dec;120(6):1260-9. doi: 10.1542/peds.2007-0971.
PubMed 18055675Radford PJ, Stillwell PC, Blue B, Hertel G. Aspiration complicating bronchopulmonary dysplasia. Chest. 1995 Jan;107(1):185-8. doi: 10.1378/chest.107.1.185.
PubMed 7813274Demirel G, Yilmaz Y, Uras N, Erdeve O, Ulu HO, Oguz SS, Dilmen U. Dramatical recovery of a mechanical ventilatory dependent extremely low birth weight premature infant after Nissen fundoplication. J Trop Pediatr. 2011 Dec;57(6):484-6. doi: 10.1093/tropej/fmq125. Epub 2011 Jan 19.
PubMed 21252395Gien J, Kinsella J, Thrasher J, Grenolds A, Abman SH, Baker CD. Retrospective Analysis of an Interdisciplinary Ventilator Care Program Intervention on Survival of Infants with Ventilator-Dependent Bronchopulmonary Dysplasia. Am J Perinatol. 2017 Jan;34(2):155-163. doi: 10.1055/s-0036-1584897. Epub 2016 Jun 29.
PubMed 27355979Newell SJ, Booth IW, Morgan ME, Durbin GM, McNeish AS. Gastro-oesophageal reflux in preterm infants. Arch Dis Child. 1989 Jun;64(6):780-6. doi: 10.1136/adc.64.6.780.
PubMed 2774613Ewer AK, Durbin GM, Morgan ME, Booth IW. Gastric emptying and gastro-oesophageal reflux in preterm infants. Arch Dis Child Fetal Neonatal Ed. 1996 Sep;75(2):F117-21. doi: 10.1136/fn.75.2.f117.
PubMed 8949695Peter CS, Sprodowski N, Bohnhorst B, Silny J, Poets CF. Gastroesophageal reflux and apnea of prematurity: no temporal relationship. Pediatrics. 2002 Jan;109(1):8-11. doi: 10.1542/peds.109.1.8.
PubMed 11773535Lopez-Alonso M, Moya MJ, Cabo JA, Ribas J, del Carmen Macias M, Silny J, Sifrim D. Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux. Pediatrics. 2006 Aug;118(2):e299-308. doi: 10.1542/peds.2005-3140. Epub 2006 Jul 10.
PubMed 16831894
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Continuous Versus Intermittent Bolus Feeding in Very Preterm Infants - Effects on Respiratory Morbidity: A Multicentre Randomised Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT03961139
- Acronym / sponsor ID
- CONFER / 2018/00773
- Keywords
- Prematurity, Randomised control trial (RCT), BPD, CLD, continuous feeding
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 3 Dec 2019 (actual)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 23 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic Lung Disease (CLD) of Prematurity is a common yet challenging co-morbidity affecting extremely premature newborns. Multifactorial influences leading to this co-morbidity is known and targeted in various research studies. Gastroesophageal reflux (GER) is common among the same cohort of patients. The investigators hypothesize that recurrent milk reflux into the airways of the premature babies worsen the inflammation of premature lungs and is a major contributor of CLD.
The investigators hypothesize that Continuous feeding (CF) minimises GER and micro-aspiration, thereby reducing the incidence and severity of CLD in high-risk infants.
Our aim is to compare the effect of intermittent bolus versus continuous intra-gastric feeding on the incidence and severity of CLD in very low birth weight infants ≤ 1250 grams.
Detailed description
The pathogenesis of bronchopulmonary dysplasia (BPD) is complex and multifactorial. As a result of premature birth, developmental arrest during a critical period of fetal lung development compounded by mechanical, oxidative and other injuries sustained during neonatal respiratory care forms the basis of pathogenesis. BPD affects up to 50% of infants with birth weight less than 1000 g. Between 2000 and 2009, despite advancement of neonatal care, annual BPD rates reported by Vermont Oxford Network among very low birth weight infants varied from 26.2% to 30.4% without any decline. Severely affected infants often require prolonged ventilation, high oxygen use, alternative airway and several potent medications over the first few months to years of their lives. High mortality rates, neurodevelopmental delay, respiratory morbidity and growth failure are associated with BPD.
Treatment of severe BPD with or without pulmonary hypertension is challenging. Prolonging the pregnancy in the face of premature labour, treating perinatal infections, augmenting pulmonary maturity with corticosteroids, judicious oxygen use, lung protective ventilation and optimizing nutrition to promote growth are important and well established measures to prevent or modify the progress of the chronic lung disease.
It is common to find infants with BPD also having significant symptoms of reflux. Gastroesophageal reflux (GER) is a well-known co-morbidity among preterms and ex-preterms on chronic ventilation, many of whom go on to require surgical fundoplication to stop the reflux thus preventing further lung damage. Some have reported dramatic respiratory improvement after resolution of GER. In the early days of a preterm baby with respiratory distress, GER is common and silent. Among infants, diagnosis of pathologic GER from a benign one is difficult. Many neonatal intensive care units (NICUs) would investigate for GER only when faced with moderate to severe BPD to achieve better respiratory symptom control. However GER has not been studied well as a factor precipitating the development of BPD among VLBW neonates. This is the focus of the study.
Aspiration of gastric contents into the lung is a widespread phenomenon in mechanically ventilated preterm infants. In animal models of gastric aspiration, gastric particulates altered the pulmonary mechanics, increased pulmonary inflammatory cells, released pro-inflammatory mediators, and inactivated surfactant. Development of bacterial pneumonia is a well-recognized complication following aspiration of gastric contents. The investigators hypothesize that repeated aspirations would aggravate and accelerate an inflammatory response in the lung finally leading on to BPD. In addition oxygen mediated damage and mechanical ventilation potentiate lung injury due to aspiration. Logically, if GER and aspiration could be minimized, it could decrease the incidence and severity of BPD.
Certain positioning of the baby, small volume of feed increment, keeping a close watch on feed tolerance are practical ways of improving feeding tolerance and reducing GER. The intermittent bolus intra-gastric feeding method is commonly used to feed premature babies. Other alternatives are continuous intra-gastric (feed volume is slowly infused in the stomach over couple of hours through the nasogastric tube) and continuous transpyloric feeding (feeding tube passes beyond the stomach to the duodenum and feed volume is slowly infused over hours). Transpyloric continuous feeding as compared to intermittent gastric bolus feeding, has been found to significantly reduce ventilatory support requirements in extremely low birth weight (ELBW) infants, possibly via its effect of minimising GER. In this study, none of the babies who received transpyloric feeding developed significant BPD and in addition babies with significant BPD improved after switching to transpyloric method. Transpyloric feeding tubes however are challenging to insert, and intestinal perforation is an uncommon but significant adverse effect. This feeding method is also not physiological as it bypasses the stomach. It remains to be seen if continuous gastric feeds, which is easily administered and safer, would yield some of the advantages of continuous transpyloric feeds over intermittent gastric feeding.
A Cochrane review in 2011 of continuous intra-gastric versus intermittent bolus intra-gastric feeding for premature infants found conflicting results, and was unable to make recommendations regarding the benefits and risks of these feeding methods. Clinical outcomes of interest from these trials were related to growth, feeding tolerance and gastrointestinal complications. The Cochrane review importantly found no significant difference in somatic growth and incidence of necrotising enterocolitis (NEC) between either feeding methods. Another Cochrane review in 2014 did not identify any randomised trial that evaluated the effects of continuous versus intermittent bolus intragastric tube feeding on gastro-oesophageal reflux disease in preterm and low birth weight infants and opined that well-designed and adequately powered trials are needed in this field. There were no studies comparing the effect of the above feeding methods on respiratory outcomes either.
Trial objectives
Aim: To compare the effect of intermittent bolus versus continuous intra-gastric feeding on the incidence and severity of BPD in very low birth weight infants (≤ 1250 grams).
Hypothesis: Continuous feeding (CF) minimises silent GER and micro-aspiration, thereby reducing the incidence and severity of bronchopulmonary dysplasia (BPD) in high-risk infants when compared to intermittent bolus feeding (BF).
Statistical considerations
Sample size calculation: based on 2015 data from the Singapore National Very-Low-Birth-Weight (VLBW) Infant Network for infants ≤ 1250 grams, mortality rate was 12.9% and BPD rate (defined as any oxygen supplementation or any respiratory support at 36 weeks post-conceptional age) was 29.4%. Thus the composite primary outcome rate was 42.3%. For a primary outcome rate reduction from 45% to 22.5%, with a type 1 error rate of 5% and a power of 80%, a sample size of 68 infants in each arm is required, giving a total sample size of 136 infants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomised-controlled trial with 2 parallel groups (1:1 ratio). Control group: intermittent bolus intra-gastric tube feeding (BF), Intervention group: continuous intra-gastric tube feeding (CF). Not blinded. Stratified randomization along following birth weight groups: 1. </=750 g 2. 751 - 1000 g 3. 1001 -1250 g Method of randomisation: Computer generated randomization codes stored in sealed opaque envelopes. Intervention started by 72 hours of life (more than trophic feed volume achieved) and continued until an infant reaches a weight of 1.6 kg and is determined by the attending Neonatologist to be ready to commence oral feeding by breast or bottle, or when an infant attains a post-conceptional age of 36 weeks, whichever is earlier. Continuous fed is delivered through a nasogastric tube by a syringe pump over 3hrs with 1 hour of break - 6 cycles a day. Feed volume, type of feed, feed increment regulated by the clinical team. Intention to treat analysis.
| Arm | Type | Receives |
|---|---|---|
| Continuous feeding (CF) | Experimental | Other: Method of feeding; continuous feeding OR bolus feedingInfants fed through a naso or orogastric tube in a continuous fashion using syringe pump. Each feed cycle is of 4 hours (3 hrs continuous feeding and 1 hour rest). 6 feed cycles in a day. Feed volume increment per day is as per departmental protocol and same as comparator arm. |
| Bolus feeding (BF) | Active comparator | Other: Method of feeding; continuous feeding OR bolus feedingInfants fed through a naso or orogastric tube in a gravity dependent bolus feeding every 2-3 hours. Each feed would take approximately 10 minutes. Feed volume increment per day is as per departmental protocol and same as experimental arm. |
Who may qualify
- Ages
- 1 day to 3 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Infants with a birth weight <1250g and a gestational age of between 24+0 - 33+6 weeks
Key exclusion criteria (6 listed)
- Major congenital malformation
- Chromosomal abnormality
- 10-minute Apgar score of =3
- Not expected to survive beyond 72 hours of age
- Bilateral grade 4 intraventricular haemorrhage (IVH)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Method of feeding; continuous feeding OR bolus feedingCF: Infants fed through a naso or orogastric tube in a continuous fashion using syringe pump. Each feed cycle is of 4 hours (3 hrs continuous feeding and 1 hour rest). 6 feed cycles in a day. BF: Infants fed through a naso or orogastric tube in a gravity dependent bolus feeding every 2-3 hours. Each feed would take approximately 10 minutes. | Other | Bolus feeding (BF), Continuous feeding (CF) |
Primary outcome
Incidence of BPD
Time frame: occurring before 36 weeks post menstrual age or 28 days of life
BPD as defined by 2001 NICHD criteria
Incidence of Death
Time frame: occurring before 36 weeks post menstrual age or 28 days of life
Death occurring before 36 weeks post menstrual age or 28 days of life
7 secondary outcomes
Invasive Ventilatory requirements
Time frame: 36 weeks post menstrual age or 28 days of life
Any Ventilatory requirements
Time frame: 36 weeks post menstrual age or 28 days of life
Supplemental Oxygen support
Time frame: 36 weeks post menstrual age or 28 days of life
Feed tolerance
Time frame: 36 weeks post menstrual age or 28 days of life
Weight outcomes
Time frame: birth, 36 weeks and 40 weeks post menstrual age
Length outcomes
Time frame: birth, 36 weeks and 40 weeks post menstrual age
Head Growth outcomes
Time frame: birth, 36 weeks and 40 weeks post menstrual age
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Background: PubMed 12667831Bancalari E, Claure N, Sosenko IR. Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol. 2003 Feb;8(1):63-71. doi: 10.1016/s1084-2756(02)00192-6.
- Background: PubMed 20732945Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, Hale EC, Newman NS, Schibler K, Carlo WA, Kennedy KA, Poindexter BB, Finer NN, Ehrenkranz RA, Duara S, Sanchez PJ, O'Shea TM, Goldberg RN, Van Meurs KP, Faix RG, Phelps DL, Frantz ID 3rd, Watterberg KL, Saha S, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010 Sep;126(3):443-56. doi: 10.1542/peds.2009-2959. Epub 2010 Aug 23.
- Background: PubMed 22614775Horbar JD, Carpenter JH, Badger GJ, Kenny MJ, Soll RF, Morrow KA, Buzas JS. Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009. Pediatrics. 2012 Jun;129(6):1019-26. doi: 10.1542/peds.2011-3028. Epub 2012 May 21.
- Background: PubMed 16322158Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, Wrage LA, Poole K; National Institutes of Child Health and Human Development Neonatal Research Network. Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics. 2005 Dec;116(6):1353-60. doi: 10.1542/peds.2005-0249.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Agnihotri Biswas, MRCPCH principal investigator
Senior Consultant Neonatologist, NUH Singapore
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Method of feeding; continuous feeding OR bolus feeding in people with Chronic Lung Disease of Prematurity and Bronchopulmonary Dysplasia, run by National University Hospital, Singapore at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Malaysia, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Agnihotri Biswas, MRCPCH (+65 67725075, biswas_agnihotri@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of BPD (time frame: occurring before 36 weeks post menstrual age or 28 days of life). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03961139, which also lists 27 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.