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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
|Official Title:||Comparison of Heparin vs. no Heparin on Duration of Peripherally Inserted Central Catheter Patency in Neonates|
- The primary outcome will be duration of catheter patency, as defined by the length of time between insertion and removal of the PICC due to catheter occlusion. [ Time Frame: 1 day to 3 months ] [ Designated as safety issue: Yes ]
- Bacteremia [ Time Frame: 1 day to 3 months ] [ Designated as safety issue: Yes ]
- Catheter-related bacteremia [ Time Frame: 1 day to 3 months ] [ Designated as safety issue: Yes ]
- Phlebitis [ Time Frame: 1 day to 3 months ] [ Designated as safety issue: Yes ]
- Thrombosis [ Time Frame: 1 day to 3 months ] [ Designated as safety issue: Yes ]
- Death [ Time Frame: 1 day to 6 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2010|
|Study Completion Date:||May 2011|
|Estimated Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
Active Comparator: Heparin group
The heparin group is the arm of the study in which all of the subjects will be treated according to current standard medical therapy. All fluids to be infused through their PICCs will have 0.5 units heparin per milliliter of intravenous fluid.
Heparin will be added to PICC infusions at a dose of 0.5 units heparin per milliliter of intravenous fluid/parenteral nutrition.
Experimental: No heparin group
This group will only receive the prescribed fluids to infuse through their PICCs. No heparin will be added to the intravenous infusions.
Drug: No heparin
In the no heparin group, the subjects will not receive heparin as an additive to their PICC infusions.
|United States, Texas|
|San Antonio, Texas, United States, 78229|
|Principal Investigator:||Aaron A Reeves, M.D.||University of Texas Health Science Center at San Antonio|
|Study Director:||Cynthia L Blanco, M.D.||University of Texas Health Science Center at San Antonio|