The Effect of Early Versus Standard Central Line Removal on Growth of Very Low Birth Weight Premature Infants

Study Overview
=================
Brief Summary
-----------------
This study compares two different regimens of a central line removal in respect to weight at 36 weeks postmenstrual age in very low birth weight (VLBW) preterm infants. Half of participants will have a central line removed at ≥100 ml/kg/d, while the other half will have a central line removed at ≥ 140 ml/kg/day.

Detailed Description
-----------------
Eligible infants will be randomized in equal proportions between two groups. In the first group (group A - early central line removal) central line will be removed at the time the infant reaches 100 ml/kg/d of enteral intake. In the second group (group B - standard central line removal) central line will be removed at the time the infant reaches 140 ml/kg/d of enteral intake (full enteral intake). Central lines will be removed after 3 well tolerated consecutive feedings (assessed by the physician) with no contraindications for central line removal present: necessity of administration of drugs that must be given via central venous access, necessity of administration of drugs that must be given intravenously along with difficulties to secure peripheral venous access, necessity of prolonged (> 7 days) administration of drugs that must be given intravenously, necessity to continue parenteral nutrition along with difficulties to secure peripheral venous access. Assessment of feedings tolerance will be at discretion of the physician taking care for the infant. After central line removal, infants in group A will continue to receive parenteral nutrition via peripheral venous access at the discretion of the physician taking care for the infant. The solution used to continue parenteral nutrition via peripheral venous access will contain at maximum 2,5% amino acids, 10% glucose and no calcium or phosphate preparations to ensure fluid's osmolality will not exceed 900 mOsm/l and the solution will be well tolerated when administered via peripheral vein. Parenteral nutrition will be prescribed according to the local protocol. Enteral nutrition will be initiated during the first days of life and advanced gradually at the discretion of the neonatologist.

Official Title
-----------------
The Effect of Early Versus Standard Central Line Removal on Growth of Very Low Birth Weight Premature Infants: A Non-inferiority, Randomized Controlled Trial

Conditions
-----------------
Growth Failure, CLABSI - Central Line Associated Bloodstream Infection

Intervention / Treatment
-----------------
* Procedure: Central line removal at 100ml/kg/day.
* Procedure: Central line removal at 140ml/kg/day.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Birth weight ≤ 1500 g (very low birth weight). Birth weight ≥ 3rd percentile at a given gestational age. Central line inserted (PICC or UVC). Oral intake not exceeding 100 ml/kg/d at randomization. Lack of congenital illness or malformation that may affect growth. Signed parental consent. Exclusion Criteria: Birth weight > 1500 g. Birth weight < 3rd percentile at a given gestational age. The absence of a central line. Oral intake ≥100 ml/kg/d at randomization. Congenital illness or malformation that may affect growth. Lack of informed consent. Participation in other intervention (investigational) trials, that may affect the primary outcome.

Ages Eligible for Study
-----------------
Maximum Age: 2 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Central line removal at 100ml/kg/day.<br>In this group central line will be removed at the time the infant reaches 100 ml/kg/day of enteral intake. Central lines will be removed after 3 well tolerated consecutive feedings (assessed by the physician) with no contraindications for central line removal present. Assessment of feedings tolerance will be at discretion of the physician taking care for the infant. After central line removal, infants in this group may continue to receive parenteral nutrition via peripheral venous access, depending on the decision of the physician taking care for the infant. Parenteral nutrition will be prescribed according to the local protocol. Enteral nutrition will be initiated during the first days of life and advanced gradually at the discretion of the neonatologist. | Procedure: Central line removal at 100ml/kg/day.<br>* In this group central line will be removed at the time the infant reaches 100 ml/kg/day of enteral intake if well tolerated.<br>|
| Active Comparator: Central line removal at 140 ml/kg/day.<br>In this group central line will be removed at the time the infant reaches 140 ml/kg/day of enteral intake (full enteral intake). In this group central line will be removed at the time the infant reaches 100 ml/kg/day of enteral intake. Central lines will be removed after 3 well tolerated consecutive feedings (assessed by the physician) with no contraindications for central line removal present. Assessment of feedings tolerance will be at discretion of the physician taking care for the infant. Parenteral nutrition will be prescribed according to the local protocol. Enteral nutrition will be initiated during the first days of life and advanced gradually at the discretion of the neonatologist. | Procedure: Central line removal at 140ml/kg/day.<br>* In this group central line will be removed at the time the infant reaches 140 ml/kg/day of enteral intake if well tolerated.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight at 36 weeks PMA. | Difference between the two intervention arms in weight at 36 weeks PMA. Noninferiority would be declared if a mean difference in weight at 36 weeks PMA will be no more than 210 g. | 36 weeks PMA. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Head circumference at 36 weeks PMA. | Difference between the two intervention arms in head circumference at 36 weeks PMA. | 36 weeks PMA. | 
| Length at 36 weeks PMA. | Difference between the two intervention arms in length at 36 weeks PMA. | 36 weeks PMA. | 
| The rate of CLABSI. | The rate of CLA-BSI in both groups. | From enrollment up to 2 days after central line removal; day of central line removal is considered Day 1. | 
| Time to regain birth weight. | If the infants remain above their birth weight for 3 consecutive days, the first day of the 3 weights will be used as the date of regaining birth weight. | Up to 4 weeks. | 
| Number of peripheral intravenous accesses inserted until discontinuation of parenteral nutrition. | Safety of early central line removal will be assessed in respect to number of peripheral intravenous accesses inserted until discontinuation of parenteral nutrition. | Up to 7 days post-intervention. | 
| Central line insertion due to feeding intolerance. | Need for central line insertion within 7 days following intervention because of feeding intolerance. | Up tp 7 days post-intervention. | 
| Weight at 18 to 22 months corrected age (CA). | Weight at the age of 18 to 22 months corrected age (CA) will be assessed for noninferiority. | At 18 to 22 months corrected age (CA). | 
| Length at 18 to 22 months corrected age (CA). | Length at the age of 18 to 22 months corrected age (CA) will be assessed for noninferiority. | At 18 to 22 months corrected age (CA) | 
| Head circumference at 18 to 22 months corrected age (CA). | Head circumference at the age of 18 to 22 months corrected age (CA) will be assessed for noninferiority. | At 18 to 22 months corrected age (CA). | 
| Length of hospital stay. | The data on the length of hospital stay expressed in days will be recorded. | Through study completion, an average of 2 years. |