Heparin Versus no Heparin on Duration of Peripherally Inserted Central Catheter (PICC) Patency in Neonates

Background: Heparin is an anticoagulant commonly used in the neonatal population as a means
to prevent catheter related occlusion and malfunction by thrombosis (clot). Given the
recent overdoses of infants using heparin, there is concern as to whether heparin should be
used in peripherally inserted central venous catheters (PICC). Scientific evidence
comparing the duration of use of heparin versus no heparin in PICCs is conflicting.

Purpose: The purpose of this study is to evaluate the effect of continuous IV fluids with
heparin versus IV fluids without heparin on the duration of percutaneously inserted central
venous catheters (PICC) in neonates.

Design: Prospective, double-blind, randomized controlled trial Hypothesis: The use of
heparin in PICC fluids has no difference on duration of catheter patency.

Design and Methods: The study will be conducted at the Neonatal Intensive Care Unit at
University Hospital, San Antonio, TX. Randomization to either the experimental group
(no-heparin) or the standard medical group (with heparin) will occur once parental consent
is obtained and prior to PICC insertion. PICC placement will be done by the PICC certified
neonatal nurses. Correct placement of the PICC will be assured by radiography which is
standard procedure.

Parents, NICU team members and staff, and investigators will be masked to the grouping.
Pharmacy will be responsible for randomization. Both the heparin group and the no heparin
group solutions will be dispensed in identical containers, compounded by the pharmacy.

The study medication, heparin, will be mixed by the pharmacy at a standard dose of 0.5
units/mL for the intravenous infusions used in the heparin group. The experimental group
will receive only the base solution, whether it is 5% dextrose, 0.9% sodium chloride, or
total parenteral nutrition infused into the PICC line. Pharmacy and the NICU staff will
ensure compatibility of heparin with other infusions. Heparin bonded catheters, heparin
flushes, and hep-lock solutions are not used by the NICU service.

The primary outcome, duration of catheter use, is defined as the time (in hours) between
insertion and removal of the catheter due to occlusion. Occlusion will be defined as the
inability to push 1 mL of 0.9% sodium chloride, via a 5 mL syringe, through the catheter in
situ or detection of clots along the catheter after removal.

Secondary outcomes include septicemia vs. catheter-related septicemia, phlebitis, death
before discharge, and thrombosis. Septicemia is identified as clinical signs and symptoms
associated with sepsis in the presence of a positive peripheral blood culture obtained
irrespective of the catheter tip culture result. Catheter-related sepsis will be defined as
positive blood culture obtained from the catheter fluid as well as a positive blood culture
obtained from a peripheral venous specimen. Both cultures must demonstrate the same
organism. Phlebitis is defined by visual detection, swelling, and change of skin color
associated with an inflamed vein. Thrombosis is defined as a thrombus along catheter path
diagnosed by visual inspection upon removal of the catheter. Elective versus non-elective
removal will also be recorded.

Adverse events monitored include: heparin induced thrombocytopenia (HIT), defined as a
platelet count dropping below 50 x 103/mL with a positive antibody titer, aPTT > 100 seconds
(This will be measured upon clinical evidence of bleeding), hemorrhage from > 2 sites,
intraventricular hemorrhage, extravasation, and dislodgement or breakage of catheter.

The sample size will be determined based on retrospective data collection to reach a
statistical power of 80% with a type I error or 0.05. The investigators expect the sample
size to be approximately 102 patients in each arm of the study.

The study will terminate once the PICC is discontinued or if there is an indication to stop
the study early for safety reasons. These could include increased adverse events in one
group versus the other. A Safety Control Panel composed of 2 neonatologists from another
site will review the data at the points when 1/3 and then 2/3 of total patient enrollment
has been achieved.

Data Collection and Analysis: Data will be collected and tabulated on a Microsoft Excel
spreadsheet using unique patient identifiers and stored at a secure location at UHS then
analyzed using appropriate statistical tests.