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

NCT02366845 | Completed Phase 4 Results DMC

• 1 other identifier: 12-0064
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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

Conditions

Liver Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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.

  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.

  within 1 hour after entire plasma transfusion

• Hospital Length of Stay

  Subjects will be followed for duration of hospital stay, anticipated within 1 Day to 28 Days

Study Arms (2)

Clinician Chosen Dosing

ACTIVE COMPARATOR

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; Diagnostic Test: Pre-Transfusion International Normalized Ratio (INR); Diagnostic Test: Post-Transfusion International Normalized Ratio (INR)

Algorithm Dosing

EXPERIMENTAL

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; Diagnostic Test: Pre-Transfusion International Normalized Ratio (INR); Diagnostic Test: Post-Transfusion International Normalized Ratio (INR)

Interventions

Fresh Frozen Plasma 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.

Also known as: FFP

Algorithm Dosing; Clinician Chosen Dosing

Pre-Transfusion International Normalized Ratio (INR) 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.

Also known as: Pre-Transfusion INR

Algorithm Dosing; Clinician Chosen Dosing

Post-Transfusion International Normalized Ratio (INR) DIAGNOSTIC_TEST

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

Also known as: Post-Transfusion INR

Algorithm Dosing; Clinician Chosen Dosing

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects will be eligible to participate in the study if they meet all of the following criteria:
• 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).
• 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
• Signs of portal hypertension (ascites, varices, hypersplenism), or
• 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)

You may not qualify if:

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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Related Publications (10)

• 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.

  PMID: 16634735 BACKGROUND

• 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.

  PMID: 15198745 BACKGROUND

• 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.

  PMID: 19150309 BACKGROUND

• 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.

  PMID: 18661920 BACKGROUND

• 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.

  PMID: 12818286 BACKGROUND

• 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

  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.

  PMID: 17626910 BACKGROUND

• 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.

  PMID: 14638344 BACKGROUND

• 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.

  PMID: 10752021 BACKGROUND

• 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.

  PMID: 20658125 BACKGROUND

MeSH Terms

Conditions

Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Results Point of Contact

• Title: Dr. Marc Moss
• Organization: University of Colorado

marc.moss@cuanschutz.edu

303-724-6080

Study Officials

• Samuel C Berngard, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Marc Moss, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2015
• First Posted: February 19, 2015
• Study Start: June 27, 2012
• Primary Completion: June 24, 2015
• Study Completion: March 27, 2019
• Last Updated: October 29, 2019
• Results First Posted: October 29, 2019

Record last verified: 2019-10

Locations

US (1)