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

Liver Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02366845
• Other study ID #: 12-0064
• Status: Completed
• Phase: Phase 4
• Start date: June 27, 2012
• Est. completion date: March 27, 2019

Study information

• Verified date: October 2019
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 27, 2019
• Est. primary completion date: June 24, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Liver Disease
• Liver Diseases

Intervention

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.

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.
• 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.

Locations

Country	Name	City	State
United States	University of Colorado Hospital	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

References & Publications (10)

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):1710-7. doi: 10.1007/s00134-010-1954-x. Epub 2010 Jul 24. — View Citation

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. Epub 2007 Jul 12. — View Citation

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. — View Citation

Maltz GS, Siegel JE, Carson JL. Hematologic management of gastrointestinal bleeding. Gastroenterol Clin North Am. 2000 Mar;29(1):169-87, vii. Review. — View Citation

Mannucci PM. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? No. J Thromb Haemost. 2006 Apr;4(4):721-3. — View Citation

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. — View Citation

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. Review. — View Citation

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

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants That Reached Targeted International Normalized Ratio (INR) Within ±0.1 After First Fresh Frozen Plasma (FFP) Transfusion Completed.	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	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.	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.
Secondary	Dose Difference (Average # Units) Between Clinician Dosing and Algorithm Dosing (Units of FFP) Per Patient.		within 1 hour after entire plasma transfusion
Secondary	Hospital Length of Stay		Subjects will be followed for duration of hospital stay, anticipated within 1 Day to 28 Days