Plasma Resuscitation Without Lung Injury

Study Overview
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Brief Summary
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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.

Official Title
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Plasma Resuscitation withOut Lung Injury

Conditions
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Burns

Intervention / Treatment
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* Drug: Pathogen-Reduced Plasma
* Drug: Crystalloid Solutions


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is an open-label, phase IV, multicenter, randomized controlled prospective clinical trial in patients with burns. The study model is parallel (between-patient). The intervention to be tested is Pathogen-Reduced Plasma for burn shock resuscitation vs. standard-of-care resuscitation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plasma<br>Pathogen-Reduced Plasma resuscitation | Drug: Pathogen-Reduced Plasma<br>* 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.<br>* Other names: PRP;|
| Active Comparator: Crystalloid<br>Standardized crystalloid resuscitation | Drug: Crystalloid Solutions<br>* 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.<br>* Other names: LR;|

What is the study measuring?
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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 |