Lactated Ringer's Solution in Neonates With Feeding Intolerance (LR)

Enteral Administration of Lactated Ringer's Solution in Neonates With Feeding Intolerance, a Randomized Controlled Trial

The objective of this study is determining if enteral administration of Lactated Ringer's solution (LR) in preterm infants with feeding intolerance enables for faster advancement of milk feeding than fasting.

Study Overview

• Status: Unknown
• Conditions: Intestinal Disease; Feeding Disorder Neonatal
• Intervention / Treatment: Drug: Lactated Ringer's Solution

Detailed Description

Feeding intolerance is a common problem in premature infants in the Neonatal Intensive Care Unit. Definition is clinical and based on abdominal distension, abdominal tenderness, emesis, change in gastric residuals, presence of blood in stool, and apnea with bradycardia.

Feeding intolerance is associated with serious complications: necrotizing enterocolitis, longer hospitalization and prolonged intravenous nutrition complications (e.g. sepsis, liver damage). Therefore, the investigators aim to achieve adequate enteral nutrition as soon as possible.

Because LR is a an amniotic fluid-like solution, it may improve gastro-intestinal function and avoid fasting, as well as its multiple problems (e.g. intestinal atrophy and decreased intestinal motility). LR was chosen as the test solution because of experience documenting its safe use in comparable groups: in newborn resuscitation parenterally, in amnioinfusion, and in bowel irrigation. Moreover, LR is similar in electrolytes composition to the experimental solution used in previous studies by Barney et al in neonates.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H3H 2R9
      • McGill University Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Birth gestational age (GA) between 25 and 32 weeks
• Corrected gestational age less than 34 weeks
• Enteral feeding tolerated at a minimum of 10 ml/kg/day for a minimum of 48 hours

• Severe feeding intolerance, defined as a minimum of one or more of the following signs leading to withholding of milk feedings on two evaluations over 12 to 24 hours:

  1. Significant increased abdominal girth, as evaluated by the treatment team, with abdominal tenderness
  2. Visible enlarged bowel loops with abdominal tenderness
  3. Recurrent emesis leading to withhold feeds
  4. Gastric residuals in excess of one feeding, recurrent or with growing abdominal girth
  5. Visible blood in stools without anal etiology
• Documented informed consent for participation in the study

Exclusion Criteria:

• Infants who already reached full enteral feeds for 72 hours, in fact a minimum of 130 ml/kg/day enteral feeds without parenteral supplementation.
• Small for gestational age (SGA) (weight at or less than the 3rd percentile on the Fenton growth chart)
• NEC (Bell's stage II or higher, radiologic evidence of NEC, pneumatosis intestinalis or free intraperitoneal air)or history of NEC
• Gastric or intestinal occlusion (no transit, absent bowel sounds, incessant vomiting, bile stained vomiting or air fluid levels)
• Major congenital malformation
• Septic infants requiring therapeutic antibiotics or antimycotics (infants only on prophylactic antibiotics or antimycotics should not be excluded).
• Patients judged as being too ill to enroll in this study, as defined by a requirement for mechanical ventilation with >50% FIO2
• Patent Ductus Arteriosus requiring ibuprofen, indomethacin or ligature, until one week after the end of treatment
• Intraventricular Haemorrhage grade 3 or 4
• Hypernatremia ≥ 150 mmol/L

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Fasting
Active Comparator: Lactated Ringer's Solution	Drug: Lactated Ringer's Solution; 2.5 ml per kg every 3 hours, via nasogastric tube, orogastric tube or orally, until the infant reaches 80 ml/kg/day of milk feeding or for a maximum of 14 days; Other Names: Lactated Ringer's

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average of the daily enteral caloric intake (in calories/kg/day) received over the 14 days after study entry	To measure enteral caloric intake, the volume of milk feeding, for each patient will be recorded daily and for 14 days. Unfortified milk and fortified milk are calculated as containing respectively 0.67 Cal/ml and 0.81 Cal/ml.	14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of days to reach 130 ml/kg milk feeding	variable
Number of days to discontinue IV access	variable
Growth (weight, height, head circumference), increase % after 14 days and between study entry and discharge home	variable
Length of hospitalization	variable
Necrotizing enterocolitis	during the 14 day-study period and hospitalization
Electrolytes, bilirubin, serum urea nitrogen, creatinine and liver enzymes	14 days
Infections	until discharge

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Gaelle Sadani, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre; Principal Investigator: Louis Beaumier, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

General Publications

• Barney CK, Lambert DK, Alder SC, Scoffield SH, Schmutz N, Christensen RD. Treating feeding intolerance with an enteral solution patterned after human amniotic fluid: a randomized, controlled, masked trial. J Perinatol. 2007 Jan;27(1):28-31. doi: 10.1038/sj.jp.7211609.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): June 1, 2012
• Study Completion (Anticipated): September 1, 2012

Study Registration Dates

• First Submitted: November 8, 2010
• First Submitted That Met QC Criteria: November 8, 2010
• First Posted (Estimate): November 9, 2010

Study Record Updates

• Last Update Posted (Estimate): August 4, 2011
• Last Update Submitted That Met QC Criteria: August 2, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Newborn; Necrotizing Enterocolitis; Intestinal Disease; Premature Infant; Lactated Ringer's Solution; Isotonic Solution; Feeding Intolerance
• Additional Relevant MeSH Terms: Mental Disorders; Digestive System Diseases; Gastrointestinal Diseases; Feeding and Eating Disorders; Intestinal Diseases
• Other Study ID Numbers: 09-225-PED