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

NCT ID: NCT02366845

Last Updated: 2019-10-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-27

Study Completion Date

2019-03-27

Brief Summary

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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

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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).

Conditions

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Liver Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Caregivers

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Fresh Frozen Plasma

Intervention Type BIOLOGICAL

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.

Pre-Transfusion International Normalized Ratio (INR)

Intervention Type DIAGNOSTIC_TEST

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.

Post-Transfusion International Normalized Ratio (INR)

Intervention Type DIAGNOSTIC_TEST

INR result after Fresh Frozen Plasma (FFP) transfusion completed, determined by clinical lab testing performed within 1 hour after transfusion completed.

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.

Group Type EXPERIMENTAL

Fresh Frozen Plasma

Intervention Type BIOLOGICAL

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.

Pre-Transfusion International Normalized Ratio (INR)

Intervention Type DIAGNOSTIC_TEST

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.

Post-Transfusion International Normalized Ratio (INR)

Intervention Type DIAGNOSTIC_TEST

INR result after Fresh Frozen Plasma (FFP) transfusion completed, determined by clinical lab testing performed within 1 hour after transfusion completed.

Interventions

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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.

Intervention Type BIOLOGICAL

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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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FFP Pre-Transfusion INR Post-Transfusion INR

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Colorado, Denver

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Samuel C Berngard, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Marc Moss, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Countries

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United States

References

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Mannucci PM. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? No. J Thromb Haemost. 2006 Apr;4(4):721-3. doi: 10.1111/j.1538-7836.2006.01886.x. No abstract available.

Reference Type BACKGROUND
PMID: 16634735 (View on PubMed)

Stanworth SJ, Brunskill SJ, Hyde CJ, McClelland DB, Murphy MF. Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials. Br J Haematol. 2004 Jul;126(1):139-52. doi: 10.1111/j.1365-2141.2004.04973.x.

Reference Type BACKGROUND
PMID: 15198745 (View on PubMed)

Tripodi A. Tests of coagulation in liver disease. Clin Liver Dis. 2009 Feb;13(1):55-61. doi: 10.1016/j.cld.2008.09.002.

Reference Type BACKGROUND
PMID: 19150309 (View on PubMed)

Iorio A, Basileo M, Marchesini E, Materazzi M, Marchesi M, Esposito A, Palazzesi GP, Pellegrini L, Pasqua BL, Rocchetti L, Silvani CM. The good use of plasma. A critical analysis of five international guidelines. Blood Transfus. 2008 Jan;6(1):18-24. doi: 10.2450/2008.0041-07.

Reference Type BACKGROUND
PMID: 18661920 (View on PubMed)

Youssef WI, Salazar F, Dasarathy S, Beddow T, Mullen KD. Role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease: a dual phase study. Am J Gastroenterol. 2003 Jun;98(6):1391-4. doi: 10.1111/j.1572-0241.2003.07467.x.

Reference Type BACKGROUND
PMID: 12818286 (View on PubMed)

Sweatt AJ, Moss M, Tripputi M, Benson AB. "A dosing formula for INR-targeted plasma transfusion in bleeding patients with chronic liver disease." American Journal of Respiratory and Critical Care Medicine 2011;183:A5828

Reference Type BACKGROUND

Gajic O, Rana R, Winters JL, Yilmaz M, Mendez JL, Rickman OB, O'Byrne MM, Evenson LK, Malinchoc M, DeGoey SR, Afessa B, Hubmayr RD, Moore SB. Transfusion-related acute lung injury in the critically ill: prospective nested case-control study. Am J Respir Crit Care Med. 2007 Nov 1;176(9):886-91. doi: 10.1164/rccm.200702-271OC. Epub 2007 Jul 12.

Reference Type BACKGROUND
PMID: 17626910 (View on PubMed)

Sorbi D, Gostout CJ, Peura D, Johnson D, Lanza F, Foutch PG, Schleck CD, Zinsmeister AR. An assessment of the management of acute bleeding varices: a multicenter prospective member-based study. Am J Gastroenterol. 2003 Nov;98(11):2424-34. doi: 10.1111/j.1572-0241.2003.t01-1-07705.x.

Reference Type BACKGROUND
PMID: 14638344 (View on PubMed)

Maltz GS, Siegel JE, Carson JL. Hematologic management of gastrointestinal bleeding. Gastroenterol Clin North Am. 2000 Mar;29(1):169-87, vii. doi: 10.1016/s0889-8553(05)70111-4.

Reference Type BACKGROUND
PMID: 10752021 (View on PubMed)

Benson AB, Austin GL, Berg M, McFann KK, Thomas S, Ramirez G, Rosen H, Silliman CC, Moss M. Transfusion-related acute lung injury in ICU patients admitted with gastrointestinal bleeding. Intensive Care Med. 2010 Oct;36(10):1710-1717. doi: 10.1007/s00134-010-1954-x. Epub 2010 Jul 24.

Reference Type BACKGROUND
PMID: 20658125 (View on PubMed)

Other Identifiers

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12-0064

Identifier Type: -

Identifier Source: org_study_id

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