Saline Enema Administration in Meconium Obstruction of Prematurity and Impact on the Resolution, Feeds, Microbiome, and Gut-brain Axis.

NCT06048614 | Recruiting DMC

• 1 other identifier: 2023/2270
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to study the effect of twice-daily saline enema (SE) in the treatment obstruction of prematurity (MOP) in infants with the birth weight ≤1.25kg. The main questions, the trial aims to answer are

1. 1.To validate the finding of our pilot study which had shown that twice-daily SE reduces the time to reach full enteral feeds in premature infant as compared to premature infant treated with Glycerine Suppository (GS), in a larger cohort. Infant with MOP fails to pass meconium in the first 48 hours of life and develop symptoms and signs like abdominal distension and feed intolerance.
2. 2.The other aims of this study are to test whether the intervention is
3. 3.Effective treatment for MOP
4. 4.Reduce the duration of ICU stay
5. 5.Reduce the rate of necrotizing enterocolitis, sepsis, Total Parenteral Nutrition (TPN) days and number of intravenous catheter days
6. 6.The study also wants to explore the impact of this intervention on the gut microbiome, gut-brain interaction and immune response of the new-born.

Conditions

Meconium Obstruction of Prematurity

Outcome Measures

Primary Outcomes (1)

• Time to reach full enteral feeds in days

  Time to reach full enteral feeds is measured from birth to the time infant reaches full oral milk feeds. Full oral milk feed is defined as milk volume of 110ml/kg/day. The total parenteral nutrition is discontinued when infant reaches milk feed volume of 110ml/kg/day. Rationale: SE loosens the thick and sticky meconium by saline absorption and triggers effective and strong peristaltic contractions, thereby leading to the evacuation of meconium from the gut. The evacuation of meconium leads to the resolution of the gut obstruction, thereby enhancing feed tolerance in premature infants with meconium obstruction of prematurity.

  Before 36 weeks of corrected age of discharge of the infant

Secondary Outcomes (4)

• Rate of treatment failure

  Before 36 weeks of corrected age of discharge of the infant

• Rate of (a) Culture positive sepsis (b) Necrotising enterocolitis.

  Before 36 weeks of corrected age of discharge of the infant

• Duration in days of (a) ICU stay (b) Total parenteral nutrition (c) PICC days.

  Before 36 weeks of corrected age of discharge of the infant

• Overall cost of care calculated in SGD at the time of discharge

  Before 36 weeks of corrected age of discharge of the infant

Other Outcomes (9)

• Identification and quantification of bacteria from meconium/stool samples by DNA sequencing and analysis of top 50 bacteria Genus

  Before 36 weeks of corrected age of discharge of the infant

• To measure the serum level of IL 6 in pg/ml

  Before 36 weeks of corrected age of discharge of the infant

• To measure the serum level of neurotransmitters noradrenaline in pg/L

  Before 36 weeks of corrected age of discharge of the infant

Study Arms (2)

Intervention Arm (Saline Enema Arm)

EXPERIMENTAL

After randomisation, infant who allocated with intervention group will proceed with SE with normal saline (20-40ml/kg twice daily) earliest at 48 to 72 hours of age. Then continue until 2 days of yellow stools/ 110ml/kg/day of oral feeds; whichever is earlier. SE are recommended if baby do not do bowel opening (BO) for 2 days before reaching full feeds

Procedure: Saline Enema (SE)

Control Arm (Glycerin Suppository Arm)

ACTIVE COMPARATOR

Infants randomized to GS received the standard management protocol for meconium retention in the unit. GS (2,000 mg, a quarter unit, four doses 12 h apart) were administered to infants earliest at 48 hour to 72 hours of birth, with subsequent once-daily GS being administered at the discretion of the managing team. Infants who were diagnosed with meconium obstruction later in the first 2 weeks of life were also treated with glycerin suppositories for 48 hrs, with subsequent once-daily GS being administered at the discretion of the managing team. Infants who failed to respond to glycerin suppositories were referred to the surgical team by the managing team The subsequent management of meconium retention was at the surgeon's discretion and included continued GS by the surgical team, contrast enema or surgical interventions performed in escalating order as mentioned.

Drug: Glycerin Suppository

Interventions

Saline Enema (SE) PROCEDURE

infant who allocated with intervention group will proceed with SE with normal saline (20-40ml/kg twice daily) at 48 hours of age. Then continue until 2 days of yellow stools/ 110ml/kg/day of oral feeds; whichever is earlier. SE are recommended if baby do not do bowel opening (BO) for 2 days before reaching full feeds Failure to resolve the MOP with SE will be designated as treatment failure and managed with contrast enema or Laparotomy by paediatric surgeons, following a formal referral.GS is not allowed in intervention arm

Intervention Arm (Saline Enema Arm)

Glycerin Suppository DRUG

Infants randomized to GS received the standard management protocol for meconium retention in the unit. GS (2,000 mg, a quarter unit, four doses 12 h apart) were administered to infants earliest at 48 hour to 72 hours of birth, with subsequent once-daily GS being administered at the discretion of the managing team. Infants who were diagnosed with meconium obstruction later in the first 2 weeks of life were also treated with glycerin suppositories for 48 hrs, with subsequent once-daily GS being administered at the discretion of the managing team. Infants who failed to respond to glycerin suppositories were referred to the surgical team by the managing team The subsequent management of meconium retention was at the surgeon's discretion and included continued GS by the surgical team, contrast enema or surgical interventions performed in escalating order as mentioned.

Control Arm (Glycerin Suppository Arm)

Eligibility Criteria

• Age: 1 Day - 36 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Criteria A: For infant presenting with early onset of MOP
• Birth weight 500 - 1250 gram
• ≥ 23 weeks gestation
• No BO for 48 hours
• BO present but with a small amount or stain of meconium
• Feeds intolerance or abdominal X-ray showing dilated loops of bowel
• Criteria B: For infant presenting with Late onset of MOP
• Birth weight 500 - 1250 gram
• ≥ 23 weeks gestation
• Infants who passed meconium initially and develop evidence of meconium obstruction at a later age (feed intolerance or vomiting and abnormal abdominal X-ray with or without abdominal distension)

You may not qualify if:

• Infants that:
• Neuromuscular disorder
• Moderate or severe asphyxia
• Inability to start enteral feeding, which continued for 3 consecutive days before 2 weeks of post-natal age for reasons unrelated to meconium inspissation or its complication
• Without parental consent
• Aggravated medical instability
• Single mothers \< 21 years

Sponsors & Collaborators

• KK Women's and Children's Hospital: lead
• Singapore General Hospital: collaborator
• Genome Institute of Singapore: collaborator
• Translational Immunology Institute: collaborator
• Duke-NUS Graduate Medical School: collaborator

Study Sites (2)

Singapore General Hospital

Singapore, 169608, Singapore

RECRUITING

KK Women's and Children Hospital

Singapore, 229899, Singapore

RECRUITING

Related Publications (21)

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MeSH Terms

Conditions

Meconium Ileus

Condition Hierarchy (Ancestors)

Intestinal Obstruction; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Thowfique Ibrahim, FRCPCH, FAMS

  Singhealth Duke-NUS Medical School, NUS and LKC Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Seow Ching Li, Biomedical

CONTACT

63948005; li.seow.ching@kkh.com.sg

Kathy Liaw, Biomedical

CONTACT

63948939; kathy.liaw.c.s@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant(Assistant Professor)

Model Details: The treatment group will receive SE with normal saline (20-40 ml/kg/per SE) 2 times a day at 48 to 72 hrs of age at the earliest. The infant with medical instability procedure will be deferred until the infant is medically fit and intervention is continued until the infant reaches full feeds, defined as 110 ml/kg/day or yellow stools whichever is earlier. SE will be recommenced if the infant does not open bowel for 2 days before reaching full feeds. In ≤ 750 grams infant, paediatric surgeons would perform the first catheterisation with 6F catheter, insertion length will be limited to 8 cm, and saline is infused with the aid of gravity. Syringe flushing is allowed if gravity force fail to drive saline to the intestine.Two ultrasound abdominal examination will be performed and first scan will coincide with first SE in 500-750 grams infants.Failure to resolve the MOP with SE will be designated as treatment failure and managed with contrast enema or Laparotomy by paediatric surgeons.

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: September 21, 2023
• Study Start: January 2, 2024
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2)