BACKGROUND:
It is important to determine whether or not prophylactic FFP is necessary for patients with mild to moderate elevation of the INR who require an invasive procedure. It is also important to establish whether routine pre-procedure coagulation tests are predictive of bleeding outcomes at the time of a significant invasive procedure. Although prophylactic FFP is often given to such patients before invasive procedures, there is little evidence to show that pre-procedure INR in this range is predictive of procedure-related bleeding or that prophylactic FFP reduces this risk.
DESIGN NARRATIVE:
After obtaining consent and verifying eligibility requirements, the study staff will randomize the patient to one of two treatment groups. One group will receive a prophylactic FFP infusion before the hepatobiliary procedure. The other group will not receive prophylactic FFP.
The dose of FFP will be approximately 10 ml/kg. The dose of FFP for each patient will be determined in one of two ways in accordance with local policies: 1) rounding to the nearest integer number of units (Method 1); or 2) using split units (Method 2). The method chosen may vary between patients (e.g., a physician might decide to dose adult patients by rounding to the nearest integer number of units and to dose pediatric patients using split units).
Method 1: The dose of FFP will be the number of units that comes closest to a dose of 10 ml/kg, determined as follows: nearest integer to (10 x weight in kg)/200. Decimals .5 and higher should be rounded up to the next integer. Decimals less than .5 should be rounded down (e.g., a 70 kg patient would receive 4 units, while a 69 kg patient would receive 3 units).
Method 2: The dose of FFP will be chosen in order to come as close as possible to a dose of 10 ml/kg, and can contain either full units, split units, or a combination thereof.
After the FFP infusion (if any) and within 2 hours prior to the hepatobiliary procedure, blood will be drawn for laboratory tests and for the repository. Although Study of Hemostasis and Invasive Procedures (SHIP) will not be a truly blinded study, the clinicians performing the hepatobiliary procedure and the radiology team performing the post-procedure ultrasound will not be told whether the participant received prophylactic FFP. They will also not know the results of the immediate pre-procedure Prethrombin Time (PT)/INR and Partial Thomboplastin Time (PTT) tests.
Participants in the study may not be treated with any other systemic hemostatic agents prior to the procedure. Local hemostatic treatments may be used during the procedure, according to standard practice. The invasive hepatobiliary procedure techniques, all other concomitant treatments and interventions, and all post-procedure treatments and interventions are at the discretion of the treating physicians. Participants will be followed for clinical evidence of bleeding and will be treated as needed for any bleeding that may occur.
Repository samples will only be used for genetic and protein tests of hemostasis, coagulation, and fibrinolysis.
SHIP is designed as a one-sided non-inferiority study. The null hypothesis is that the proportion of patients not given prophylactic FFP who meet the criteria for the bleeding endpoint is at least .04 higher than the proportion of patients given prophylactic FFP who meet the criteria for the bleeding endpoint. The goal of this study is to determine whether there is strong evidence that the difference between the two treatment plans is not that large.
