Fresh-Frozen Plasma Infusions to Reduce Risk of Bleeding Related to Invasive Procedures
This study will compare patients with mild to moderate prolongation of the INR test who receive FFP infusions prior to invasive hepatobiliary procedures for bleeding complications to patients who do not receive FFP infusions. Bleeding complications will be defined as meeting one or more of the following:
- Intrahepatic hematoma greater than 1 ml/kg of patient weight as seen on post-procedure ultrasound examination performed between 4 to 30 hours after the procedure.
- Greater than 1.6g/dL hemoglobin decline measured within 4 to 30 hours post-procedure compared with the pre-procedure value, in the absence of another identified bleeding source to account for the hemoglobin drop.
- Need for transfusion of packed red blood cells for procedure-related bleeding while in the study.
The secondary endpoints of this study will be: 1) The need to perform subsequent procedures (angiography, embolization, additional imaging study including computerized tomography (CT) scan, surgery) to diagnose or to arrest procedure-related bleeding OR the need for subsequent medical therapies (FFP, coagulation factor concentrates, anti-fibrinolytics) to treat procedure-related bleeding between time of procedure and the end of patient's time in the study. If necessary, the relationship of procedure or therapy to procedure-related bleeding will be assessed by an adjudication panel; 2) The predictive value of INR; 3) The effect of study treatment on change in INR; 4) The cost of preventing one bleed; 5) The predictors of bleeding other than INR; 6) The number of transfusion-associated adverse events encountered to prevent one bleed; and 7) The effect of treatment on bleeding grade.
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Study of Hemostasis and Invasive Procedures (SHIP: A TMH CTN Study)|
- Clinically significant bleeding (measured 4 to 30 hours after invasive hepatobiliary procedure)
|Study Start Date:||March 2006|
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.
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.
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|United States, Iowa|
|University of Iowa Hospitals and Clinics|
|Iowa City, Iowa, United States, 52242|
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|University of Maryland Medical Center|
|Baltimore, Maryland, United States, 21201|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|Weill Medical College of Cornell University|
|New York, New York, United States, 10021|
|United States, North Carolina|
|University of North Carolina Hospital|
|Chapel Hill, North Carolina, United States, 27514|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|University of Pittsburgh Presbyterian and Shadyside Hospital|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Texas|
|University of Texas SW Medical Center|
|Dallas, Texas, United States, 75390|
|United States, Washington|
|Puget Sound Blood Center Div of Research|
|Seattle, Washington, United States, 98104|
|United States, Wisconsin|
|Blood Center of SE Wisconsin|
|Milwaukee, Wisconsin, United States, 53201|
|Principal Investigator:||Susan Assmann, PhD||New England Research Institutes, Inc.|
|Principal Investigator:||Mark Brecher, MD||University of North Carolina Hospital|
|Principal Investigator:||George Buchanan, MD||University of Texas SW Medical Center|
|Principal Investigator:||James Bussel, MD||Weill Medical College of Cornell University|
|Principal Investigator:||John Hess, MD, MPH||University of Maryland|
|Principal Investigator:||Christopher D. Hillyer, MD||Emory University|
|Principal Investigator:||Barbara Konkle, MD||University of Pennsylvania|
|Principal Investigator:||David Kuter, MD||Massachusetts General Hospital|
|Principal Investigator:||Jeffrey McCullough, MD||University of Minnesota - Clinical and Translational Science Institute|
|Principal Investigator:||Janice McFarland, MD||Blood Center of SE Wisconsin|
|Principal Investigator:||Paul Ness, MD||Johns Hopkins University|
|Principal Investigator:||Thomas Ortel, MD, PhD||Duke University|
|Principal Investigator:||Sherrill J. Slichter, MD||Puget Sound Blood Center Div of Research|
|Principal Investigator:||Ronald Strauss, MD||University of Iowa|
|Principal Investigator:||Darrell Triulzi, MD||University of Pittsburgh Presbyterian and Shadyside Hospital|
|Principal Investigator:||James R. Stubbs, MD||Mayo Clinic|