Fresh Frozen Plasma vs Albumin for Burns

(FFP Trial)

Overseen By Blaire Balstad, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Disqualifiers: Pregnancy, Renal failure, Coagulopathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 hours

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators propose a prospective randomized trial to study fresh frozen plasma (FFP) versus albumin to determine the optimal colloid in burn resuscitations. This work addresses both FY20 focus areas, prolonged field care (PFC) and en route care, along with mitigating secondary effects of acute intervention, such as prevention of over resuscitation. Future military conflicts anticipate more extensive burn and blast injuries, and delayed evacuation. Therefore, the direct comparison of colloids used in burn resuscitation is critical to advancing battlefield medicine. Specifically, this work will provide the foundation for the use of freeze-dried plasma (FDP) in burn care by medical responders in PFC and en route care scenarios. The investigators hypothesize that FFP administration, and later FDP, in burn resuscitation is as safe as albumin, and more efficacious, in both reducing the total volume of fluid required in acute burn resuscitation and correcting burn endotheliopathy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Fresh Frozen Plasma for burns?

Research shows that Fresh Frozen Plasma (FFP) is effective in treating severe burns by improving blood volume and reducing fluid needs, which helps in faster recovery. It is also safer now with reduced risks of disease transmission. ^{1 2 3 4 5}

Is fresh frozen plasma (FFP) generally safe for use in humans?

Fresh frozen plasma (FFP) is generally safe but can have side effects like allergic reactions, fever, and more serious issues like transfusion-related acute lung injury. It's important to use FFP appropriately to minimize these risks. ^{1 6 7 8 9}

How does fresh frozen plasma treatment differ from other treatments for burns?

Fresh frozen plasma (FFP) is unique in burn treatment because it helps improve blood clotting and expand blood volume, which can be crucial for patients with severe burns. Unlike albumin, FFP contains clotting factors that can reduce bleeding risks, but it may carry higher costs and risks of viral transmission. ^{1 2 10 11 12}

Eligibility Criteria

This trial is for children and young adults aged 2-18 with severe burns covering more than 20% of their body, seen at UCH Burn Center within 8 hours of injury. It excludes those who can't receive blood products, have severe coagulation or liver issues, are prisoners, pregnant, or have certain types of injuries or kidney disease.

Inclusion Criteria

I am a child (2-18 years) with burns covering more than 20% of my body, seen within 8 hours of the injury.

Exclusion Criteria

You have severe injuries that are life-threatening.

I have moderate to severe liver cirrhosis.

Coagulopathy (admission INR >2.5)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Fresh Frozen Plasma (FFP) or Albumin for burn resuscitation

24 hours

In-hospital treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measuring fluid volume and complications

3 years

Treatment Details

Interventions

• Fresh Frozen Plasma

Trial Overview The study compares the use of fresh frozen plasma (FFP) versus albumin in acute burn resuscitation to see which is better for managing fluid needs and correcting endothelial damage caused by burns. The goal is to improve care in prolonged field scenarios.

Participant Groups

Group I: Fresh Frozen Plasma Active Control 1 Intervention

At 6-8 hours, Initiate FFP infusion

Group II: Albumin Active Control 1 Intervention

At 7 hours, Initiate 5% Albumin infusion

Fresh Frozen Plasma is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fresh Frozen Plasma for:

• Acute burn resuscitation
• Coagulopathy correction
• Volume expansion in shock

Approved in European Union as Fresh Frozen Plasma for:

• Acute burn resuscitation
• Coagulopathy correction
• Volume expansion in shock

Approved in Canada as Fresh Frozen Plasma for:

• Acute burn resuscitation
• Coagulopathy correction
• Volume expansion in shock

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

In a study of 209 patients with severe burns covering more than 30% of their body, those treated with fresh frozen plasma (FFP) had a significantly lower mortality rate (33.8%) compared to those treated with albumin (78.9%).

The findings suggest that the type of colloid treatment used in burn patients can greatly impact survival rates, highlighting the potential benefits of using FFP over albumin in managing severe burn injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Albumin and Fresh Frozen Plasma as Colloid Therapy in Patients With Major Burns. Vural, S., Yasti, CA., Dolapçı, M.[2023]

Colloids, such as fresh frozen plasma and albumin, are effective in improving fluid balance and reducing swelling in patients with major burns, as they enhance intravascular volume and osmotic pressure.

While fresh frozen plasma is effective for burn resuscitation, it carries risks like viral transmission and lung injury; albumin is a safer and more cost-effective alternative that also reduces the need for additional fluids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colloids in Acute Burn Resuscitation. Cartotto, R., Greenhalgh, D.[2017]

Early administration of fresh frozen plasma (FFP) in a large animal model of traumatic brain injury (TBI) and hemorrhagic shock (HS) significantly reduced neurologic impairment and accelerated recovery over a 30-day period, compared to normal saline treatment.

FFP-treated animals showed a trend towards smaller brain lesions and were able to participate in cognitive testing 8 days earlier than those treated with saline, indicating improved cognitive function preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early resuscitation with fresh frozen plasma for traumatic brain injury combined with hemorrhagic shock improves neurologic recovery. Halaweish, I., Bambakidis, T., He, W., et al.[2022]

Fresh frozen plasma (FFP) is a safe and effective volume expander that can reduce the overall fluid requirements during acute burn resuscitation, potentially improving patient outcomes.

Newer forms of plasma, such as solvent-detergent-treated plasma and lyophilized plasma, may offer even greater safety and efficacy, warranting further investigation as adjuncts in burn treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review on the Use of Plasma During Acute Burn Resuscitation. Cartotto, R., Callum, J.[2021]

In a study of 586 adult burn patients, using a higher ratio of frozen plasma to plasma substitutes (≥2:1) within 48 hours of admission significantly improved 30-day survival rates and reduced in-hospital mortality compared to lower ratios.

The study found that a greater burn area was an independent risk factor for 30-day mortality, while a higher infusion ratio of frozen plasma was identified as a protective factor, suggesting that optimizing plasma use can enhance patient outcomes in severe burn cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the infusion ration between frozen plasma and plasma substitutes on the prognosis of adult patients with major burn in shock stage. Xiao, K., Zhao, F., Wan, J., et al.[2021]

Solvent/detergent-treated plasma (SDP) and fresh-frozen plasma (FFP) have similar levels of most coagulation factors, but FFP contains significantly higher concentrations of factors V, von Willebrand factor, and ADAMTS-13, which are important for blood clotting.

Cytokine levels, including TNF-α, IL-8, and IL-10, were also higher in FFP compared to SDP, indicating that FFP may have a broader range of immune response factors, although the clinical significance of these differences needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative concentrations of haemostatic factors and cytokines in solvent/detergent-treated and fresh-frozen plasma. Theusinger, OM., Baulig, W., Seifert, B., et al.[2018]

In a study of 33 critically ill patients, transfusion of fresh frozen plasma (FFP) significantly reduced levels of the inflammatory cytokine TNF-α, indicating a potential anti-inflammatory effect.

FFP transfusion also improved endothelial condition by decreasing syndecan-1 and factor VIII levels while increasing ADAMTS13, suggesting a stabilization of the endothelial lining, which is important for vascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of transfusion of fresh frozen plasma on parameters of endothelial condition and inflammatory status in non-bleeding critically ill patients: a prospective substudy of a randomized trial. Straat, M., Müller, MC., Meijers, JC., et al.[2022]

Fresh frozen plasma (FFP) is effective for actively bleeding patients with multiple coagulation factor deficiencies and for preventing dilutional coagulopathy in major trauma cases, but current dosing recommendations may be inadequate.

Transfusing FFP to non-bleeding patients with mild coagulation issues is not supported by evidence and poses unnecessary risks, including serious complications like transfusion-related acute lung injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative coagulation management--fresh frozen plasma. Kor, DJ., Stubbs, JR., Gajic, O.[2019]

A systematic review of 10 studies found that organizational interventions significantly reduced the risk of inappropriate fresh-frozen plasma (FFP) transfusions, with a risk ratio of 2.02 before interventions compared to after.

Implementing these interventions is crucial for improving clinician practices and ensuring safer transfusion procedures, thereby promoting better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Appropriateness of fresh-frozen plasma usage in hospital settings: a meta-analysis of the impact of organizational interventions. Damiani, G., Pinnarelli, L., Sommella, L., et al.[2019]

A systematic review of 15 trials involving 755 participants found no significant difference in mortality rates for patients undergoing cardiovascular surgery who received fresh frozen plasma (FFP) compared to those who did not, indicating that FFP may not be effective as a prophylactic treatment in this context.

FFP transfusion was associated with a higher likelihood of requiring red cell transfusions, suggesting that while it may improve prothrombin time, it does not translate into clinical benefits for reducing blood loss or mortality in elective cardiac surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fresh frozen plasma for cardiovascular surgery. Desborough, M., Sandu, R., Brunskill, SJ., et al.[2022]

In a study involving 24 splenectomized dogs, resuscitation from hemorrhagic shock using fresh-frozen plasma (FFP) alongside red blood cells (PRBCs) and electrolyte solution resulted in improved cardiac output and left ventricular stroke work compared to controls.

FFP resuscitation did not negatively affect the balance of pulmonary capillary wedge pressure and left ventricular stroke work ratio, suggesting it is a safe alternative volume expander that maintains protein levels in the bloodstream.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of fresh-frozen plasma resuscitation on cardiopulmonary function and serum protein flux. Lucas, CE., Martin, DJ., Ledgerwood, AM., et al.[2019]

A study of 392 children with burns showed that implementing blood conserving techniques during surgery led to significant reductions in the use of blood products, including a 100% reduction in fresh frozen plasma (FFP) for small burns and up to 89% reduction in packed red blood cells (pRBC) for small burns.

Despite these reductions in blood product use, patient survival rates remained high, with 97% in the first group and 98% in the second group, indicating that these blood conservation strategies do not compromise patient safety or clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in blood conservation in burn care. Sheridan, RL., Szyfelbein, SK.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparison of Albumin and Fresh Frozen Plasma as Colloid Therapy in Patients With Major Burns. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Colloids in Acute Burn Resuscitation. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

Early resuscitation with fresh frozen plasma for traumatic brain injury combined with hemorrhagic shock improves neurologic recovery. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A Review on the Use of Plasma During Acute Burn Resuscitation. [2021]

5. China pubmed.ncbi.nlm.nih.gov

Effect of the infusion ration between frozen plasma and plasma substitutes on the prognosis of adult patients with major burn in shock stage. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Relative concentrations of haemostatic factors and cytokines in solvent/detergent-treated and fresh-frozen plasma. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Effect of transfusion of fresh frozen plasma on parameters of endothelial condition and inflammatory status in non-bleeding critically ill patients: a prospective substudy of a randomized trial. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Perioperative coagulation management--fresh frozen plasma. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Appropriateness of fresh-frozen plasma usage in hospital settings: a meta-analysis of the impact of organizational interventions. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Fresh frozen plasma for cardiovascular surgery. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Effect of fresh-frozen plasma resuscitation on cardiopulmonary function and serum protein flux. [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Trends in blood conservation in burn care. [2019]