Prospective Validation of a Plasma Transfusion Dosing Algorithm in Patients With Chronic Liver Disease

October 7, 2019 updated by: University of Colorado, Denver

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University Of Colorado Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Clinician Chosen Dosing

Admitted University of Colorado Hospital or Denver Health bleeding patients with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. The total dose will be determined by the physician's judgment which is the current standard of care. The physician chosen dose will be utilized but physician will be unaware of which dosing strategy has been utilized.

INR measurements will be performed before (pre) and after (post) transfusion of plasma has been administered. Primary and secondary outcome measures will be collected. No other transfused blood component, crystalloid or colloidal fluid will be infused between the first and second INR studies except plasma.
Biological: Fresh Frozen Plasma
An INR dose-response curve with associated transfusion algorithm was generated for plasma in bleeding patients with chronic liver disease. In the intervention arm we will determine the plasma transfusion dose using the algorithm dosing table based on the pre-transfusion INR and the clinician chosen INR target. In the usual care group the dosing will be determined by the clinician.
Other Names:
  • FFP
Diagnostic test: Pre-Transfusion International Normalized Ratio (INR)
INR result prior to Fresh Frozen Plasma (FFP) transfusion determined by clinical lab testing performed within 6 hours to 1 day before transfusion start time.
Other Names:
  • Pre-Transfusion INR
Diagnostic test: Post-Transfusion International Normalized Ratio (INR)
INR result after Fresh Frozen Plasma (FFP) transfusion completed, determined by clinical lab testing performed within 1 hour after transfusion completed.
Other Names:
  • Post-Transfusion INR
Experimental: Algorithm Dosing

Admitted University of Colorado Hospital or Denver Health bleeding patients with chronic liver disease determined to receive fresh frozen plasma (FFP) for clinical indications as determined by hospital clinician. This group will receive plasma doses based on the study dosing algorithm table.

A pre-transfusion INR (before transfusion) and a target post-transfusion INR (after transfusion) will be used to determine dose of FFP. The study table will reveal the dose in (ml/kg) of FFP to be transfused. INR measurements will be performed before (pre) and after (post) transfusion of plasma has been administered. Primary and secondary outcome measures will be collected. No other transfused blood component,crystalloid or colloidal fluid will be infused between the first and second INR studies except plasma.
Biological: Fresh Frozen Plasma
An INR dose-response curve with associated transfusion algorithm was generated for plasma in bleeding patients with chronic liver disease. In the intervention arm we will determine the plasma transfusion dose using the algorithm dosing table based on the pre-transfusion INR and the clinician chosen INR target. In the usual care group the dosing will be determined by the clinician.
Other Names:
  • FFP
Diagnostic test: Pre-Transfusion International Normalized Ratio (INR)
INR result prior to Fresh Frozen Plasma (FFP) transfusion determined by clinical lab testing performed within 6 hours to 1 day before transfusion start time.
Other Names:
  • Pre-Transfusion INR
Diagnostic test: Post-Transfusion International Normalized Ratio (INR)
INR result after Fresh Frozen Plasma (FFP) transfusion completed, determined by clinical lab testing performed within 1 hour after transfusion completed.
Other Names:
  • Post-Transfusion INR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants That Reached Targeted International Normalized Ratio (INR) Within ±0.1 After First Fresh Frozen Plasma (FFP) Transfusion Completed.
Time Frame: within 1 hour after entire plasma transfusion

Ability of dosing algorithm to accurately predict necessary plasma dose (ml/kg), required to reach commonly targeted International Normalized Ratio (INR) values, compared to clinician chosen plasma transfusion dose, as determined by dose-response curve.

The primary outcome was achievement of the target INR within ±0.1 after the first round of FFP transfusion. This primary outcome 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).
within 1 hour after entire plasma transfusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: hours from first dose to initiation of procedure, anticipated timeframe between 1 minute to 8 hours.
Decreased time between initiation of plasma infusion, achieving a corrected target INR and start of planned patient procedures would potentially improve care efficiency and/or allow faster intervention in unstable patients.
hours from first dose to initiation of procedure, anticipated timeframe between 1 minute to 8 hours.
Dose Difference (Average # Units) Between Clinician Dosing and Algorithm Dosing (Units of FFP) Per Patient.
Time Frame: within 1 hour after entire plasma transfusion
within 1 hour after entire plasma transfusion
Hospital Length of Stay
Time Frame: Subjects will be followed for duration of hospital stay, anticipated within 1 Day to 28 Days
Subjects will be followed for duration of hospital stay, anticipated within 1 Day to 28 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Investigators

  • Principal Investigator: Samuel C Berngard, MD, University of Colorado, Denver

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 27, 2012

Primary Completion (Actual)

June 24, 2015

Study Completion (Actual)

March 27, 2019

Study Registration Dates

First Submitted

February 4, 2015

First Submitted That Met QC Criteria

February 11, 2015

First Posted (Estimate)

February 19, 2015

Study Record Updates

Last Update Posted (Actual)

October 29, 2019

Last Update Submitted That Met QC Criteria

October 7, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12-0064

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe