Clinical trial NCT02366845: Prospective Validation of a Plasma Transfusion Dosing Algorithm in Patients With Chronic Liver Disease
Official title: Prospective Validation of a Plasma Transfusion Dosing Algorithm in Patients With Chronic Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Liver Disease
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2015-02-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study plans to learn more about transfusion of a human blood component called plasma in patients who have liver problems. Patients are asked to be in this study because they have liver disease and therefore may require the transfusion of plasma.

The dose of plasma required to reach certain blood clotting laboratory targets is usually determined by clinicians. Due to the complexity of the patient's blood clotting disorder, determining the appropriate dose of plasma is very difficult. The investigators have developed a dosing table based on information from other patients with liver disease and the investigators are testing it to see if it is a more accurate dosing tool then clinician chosen dosing of plasma in patients with liver disease who need one or more plasma transfusions

Detailed description: Clinicians currently transfuse plasma to International Normalized Ratio (INR) targets without an understanding of the dose response characteristics of plasma in bleeding patients with liver disease. Epidemiologic studies show that INR is infrequently corrected to target INR values after clinician chosen plasma transfusion doses in patients with liver disease. Plasma transfusion is frequently given to patients prior to procedures and during active bleeding in this patient population though there are no dosing guidelines to aid clinicians in reaching INR targets in patients with liver disease. Previous studies suggest that patients with liver disease may need more plasma then patients without liver disease to correct any given pre-transfusion INR (INR value measured before plasma transfusion) to the same post-transfusion INR target (INR value measured after plasma transfusion).

Current physician dosing of plasma is variable and rarely successful at reaching stated INR targets. The INR thresholds, commonly used triggers for plasma transfusion by Gastro-Intestinal (GI), Hepatology and critical care physicians at our institution range from 1.5-3.0 in bleeding or pre-procedural patients with liver disease representing tremendous variability. When we evaluated plasma transfusion dosing practices in bleeding patients with liver disease over 8 years, we demonstrated that these same physicians rarely met stated theoretical targets.

Over or under dosing plasma in these patients may lead to serious clinical complications.The target INR goal was to be within ±0.1 after the first round of FFP transfusion, and was selected because underdosing can result in prolonged bleeding, delayed procedure times, and more rounds of FFP transfusion. Furthermore, overdosing can result in excess cost, increased portal pressures, bleeding, transfusion associated circulatory overload (TACO), and transfusion related acute lung injury (TRALI).

Eligibility criteria: Inclusion Criteria:

Subjects will be eligible to participate in the study if they meet all of the following criteria:

1. Admission to the University of Colorado Hospital or Denver Health hospital and the clinical care team plans to transfuse the patient plasma to target a specific INR value. (reason for transfusion is not considered).
2. Patient has chronic liver disease defined as 1 or more of the following: Previous diagnosis of chronic liver disease OR -Imaging or biopsy diagnosis of cirrhosis; or
3. Signs of portal hypertension (ascites, varices, hypersplenism), or
4. Laboratory evidence of synthetic dysfunction (INR\>1.5, bilirubin\> 2.0 mg/dL, albumin\<2.5 mg/dL) AND ≥2 physical exam findings on admission associated with chronic liver disease (palmar erythema, spider angiomata, asterixis, caput medusa, gynecomastia)

Exclusion Criteria Subjects will be ineligible to participate in the study if they meet any of the following criteria

1. Patient under age 18
2. Patient actively taking vitamin K antagonists
3. Inability to obtain consent
4. Clinical team does not desire to target a specific INR value
5. Pregnant patients and prisoners
6. Patients with Acute Liver Failure

Primary outcomes:
measure: Number of Participants That Reached Targeted International Normalized Ratio (INR) Within ±0.1 After First Fresh Frozen Plasma (FFP) Transfusion Completed.
timeFrame: within 1 hour after entire plasma transfusion
Secondary outcomes:
measure: Time (Hours) From Initiation of First Dose of Plasma to Initiation of Planned Procedure (in Patient Undergoing Transfusion Before a Procedure) for Clinician Dosing Compared to Algorithm Dosing Strategies.
timeFrame: hours from first dose to initiation of procedure, anticipated timeframe between 1 minute to 8 hours.
measure: Dose Difference (Average # Units) Between Clinician Dosing and Algorithm Dosing (Units of FFP) Per Patient.
timeFrame: within 1 hour after entire plasma transfusion
measure: Hospital Length of Stay
timeFrame: Subjects will be followed for duration of hospital stay, anticipated within 1 Day to 28 Days
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Samuel C Berngard, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Marc Moss, MD
role: PRINCIPAL_INVESTIGATOR
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