Plasma Resuscitation Without Lung Injury (PROPOLIS)

Plasma Resuscitation withOut Lung Injury

The treatment of patients with major burns requires resuscitation with massive amounts of fluid, typically a type of salt water that is given by vein. This frequently results in injury to vital organs, especially the lungs and kidneys, and even in death. In this study, the investigators propose to use plasma, a specially prepared blood product made from the liquid part of blood, that has undergone special treatment to reduce the risk of disease transmission. The aims include 1) reduce the amount of fluid given during the first 24 hours after a burn 2) reduce the incidence of lung injury and other complications related to the administration of funds and 3) determine if the blood product has any effect on inflammation. An overall decrease the amount of fluids that burn patients receive should decrease the potential for lung injury, decrease days in the hospital, and improve survival.

Study Overview

• Status: Recruiting
• Conditions: Burns
• Intervention / Treatment: Drug: Pathogen-Reduced Plasma; Drug: Crystalloid Solutions

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Monica Phillips, MBA; Phone Number: 210-884-3410; Email: monica@nattrauma.org
• Study Contact Backup: Name: Michelle Price, PhD; Phone Number: 210-455-8038; Email: michelle@nattrauma.org

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham Burn Center
      • Contact: Shannon Stephens; Phone Number: 205-934-5890; Email: swstephens@uabmc.edu
      • Principal Investigator: Jan Jensen, MBBS, Phd
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Not yet recruiting
      • University of Maryland School of Medicine
      • Contact: Rosemary Kozar, MD; Phone Number: 410-328-3495; Email: rkozar@som.umaryland.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Sarah Folliard, BSN; Phone Number: 615-936-2876; Email: sarah.folliard@vumc.org
      • Principal Investigator: Robel Beyene, MD
  • Texas
    • Dallas, Texas, United States, 75390
      • Withdrawn
      • University of Texas Southwestern
    • Fort Sam Houston, Texas, United States, 78234-6315
      • Recruiting
      • U.S. Army Burn Center
      • Contact: Shannon Gutierrez, BSN; Phone Number: 210-916-0990; Email: shannon.gutierrez4.ctr@health.mil
      • Principal Investigator: Leopoldo Cancio, MD
    • Galveston, Texas, United States, 77555
      • Not yet recruiting
      • University of Texas Medical Branch
      • Principal Investigator: Steven Wolf, MD
      • Contact: Elizabeth Hennessy; Email: eahennes@utmb.edu
  • Washington
    • Seattle, Washington, United States, 98104-2499
      • Active, not recruiting
      • University of Washington School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18 years
• Weight > 40 kg
• Initial assessment of thermal injury size ≥ 20% TBSA
• Admitted to the burn center and enroll able within 8 hours of injury
• Expected to receive intravenous resuscitation fluids for at least 24 hours after injury
• Expected to live > 24 hours after injury

Exclusion Criteria:

• Chemical injury
• Deep electric injury
• Associated non-thermal injuries with estimated Injury Severity Score > 25
• Inability to obtain informed consent
• Decision not to treat due to injury severity or other factors
• Patient age > 65 years or < 18 years
• Presence of anoxic brain injury that is not expected to result in complete recover
• Patent already receiving plasma infusion, or judged to be likely to require plasma infusion
• Patent already receiving "rescue procedures" (albumin infusion, CRRT, TPE, or high-dose ascorbic acid)
• Existence of pre-morbid conditions: Congestive heart failure (NYHA Class IV); End-stage kidney disease (dialysis patient); Cirrhosis of the liver; Oxygen-dependent chronic obstructive pulmonary disease; Malignancy currently under treatment; Previous bilateral lower extremity amputations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plasma; Pathogen-Reduced Plasma resuscitation	Drug: Pathogen-Reduced Plasma; The treatment group will receive an additional infusion of Pathogen-Reduced Plasma based on the formula, hourly rate, mL/hr = (1 mL*kg*TBSA)/24 hr. This infusion will not be titrated. It will be discontinued at the end of the 24th postburn hour.; Other Names: PRP
Active Comparator: Crystalloid; Standardized crystalloid resuscitation	Drug: Crystalloid Solutions; The control group will receive an additional infusion of LR based on the formula: hourly rate, mL/hr = (1mL*kg*TBSA)/24 hr. this infusion will not be titrated. It will be discontinued at the end of the 24th postburn hour.; Other Names: LR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The total volume of all resuscitation fluids delivered between hours 0-24 postern, in ml/kg.	The total volume of all resuscitation fluids delivered between hours 0-24 postburn, in ml/kg	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total resuscitation volume in ml/kg	The total volume of all resuscitation fluids delivered between hours 0-48 postburn, in ml/kg	48 hours
Total 24 hour resuscitation volume in ml/kg/TBSA	The total volume of all resuscitation fluids delivered between hours 0-24 postburn, in ml/kg/TBSA	24 hours
Total 48 hour resuscitation volume in ml/kg/TBSA	The total volume of all resuscitation fluids delivered between hours 0-48 postburn, in ml/kg/TBSA	48 hours
Hemodynamic instability	Severity and duration of hemodynamic instability during hours 0-48 postburn (norepinephrine equivalents)	48 hours
Metabolic acidosis	Severity and duration of metabolic acidosis (arterial lactate levels)	48 hours
Incidence of "rescue" (a)	Initiation of extracorporeal therapy (continuous renal replacement therapy or therapeutic plasma exchange	48 hours
Incidence of "rescue" (b)	Infusion of high-dose ascorbic acid (66 mg/kg/hr)	48 hours
Incidence of "rescue" (c)	Initiation of a continuous infusion of albumin	24 hours
Acute Respiratory Distress Syndrome	Incidence of Acute Respiratory Distress Syndrome using Berlin Criteria	7 days
Mechanical ventilation	Ventilator free days	28 days
Intensive Care Unit days	Intensive Care Unit free days	28 days
Multi-Organ Failure Assessment	Sequential Organ Failure Assessment scores. Minimum score 1, maximum score 4. The higher the score the worse the outcome.	7 days
Transfusion-Related Acute Lung Injury	Incidence of Transfusion-Related Acute Lung Injury, Type I or II.	72 hours
Thromboembolic events	Incidence of venous thrombosis-embolic events (deep vein thrombosis or pulmonary embolism)	7 days
Mortality	In hospital mortality	throughout study completion, an average of 1 year
Patient reported outcomes	Patient reported outcomes using the Patient Reported Outcomes Measurement Information System, Global 10. This scale10-item patient-reported questionnaire in which the response options are presented as 5-point (as well as a single 11-point) rating scales. The results of the questions are used to calculate two summary scores: a Global Physical Health Score and a Global Mental Health score. Higher scores equal a healthier patient.	6 months
Syndecan-1 levels	Syndecan-1 level in ng/dl	48 hours
Cytokines	Cytokines	48 hours

Collaborators and Investigators

• Sponsor: Coalition for National Trauma Research
• Collaborators: Cerus Corporation
• Investigators: Principal Investigator: Leopoldo Cancio, MD, U.S. Army Burn Center

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Estimated): June 29, 2024
• Study Completion (Estimated): September 29, 2024

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: December 19, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Lung Injury
• Other Study ID Numbers: CNTR-2020-001; CDMRP-DM190167 (Other Grant/Funding Number: Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Data will become available one year after initial results publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes