Safety And Field Evaluation of Plasma Lyophilized for Acute and Surgical Management Applications (SAFE-PLASMA)

A Phase 4, Cluster-Randomized Crossover, Prospective, Multi-Center Trial Evaluating the Safety of Freeze-Dried Plasma and Conventional Plasma Products in Adult Patients

The purpose of this study is to compare the safety of freeze-dried plasma (FDP), known as EZPLAZ, with conventional plasma in adults who need a plasma transfusion. Plasma is the liquid part of blood that contains proteins that help blood clot. The main question is whether the risk of blood clots or death within 7 days after the first transfusion is not unacceptably higher with FDP than with conventional plasma.

Participating hospitals will follow a randomly assigned schedule that determines which plasma product enrolled participants receive during each week. Participants will receive the product assigned to their hospital for that week during the first 24 hours of treatment. The treating physician will determine how much plasma is needed. After the first 24 hours, participants may receive either product if additional plasma is required.

Participants will be followed for 28 days after their first study transfusion. Information about blood clots, transfusion reactions, or other medical problems, and survival. Trial information will come from routine medical care and medical records. Follow-up after hospital discharge may include telephone contact with the participant or their legally authorized representative. No additional laboratory tests are required solely for this study.

Study Overview

• Status: Not yet recruiting
• Conditions: Thromboembolic Event; FDP
• Intervention / Treatment: Biological: Freeze-Dried Plasma; Biological: Conventional Plasma

• Study Type: Interventional
• Enrollment (Estimated): 867
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must be aged ≥ 18 years old and require plasma transfusion for one of the following indications:

1. Management of preoperative or bleeding patients who require replacement of multiple plasma coagulation factors (e.g., liver disease, disseminated intravascular coagulation [DIC])
2. Patients undergoing massive transfusion who have clinically significant coagulation deficiencies
3. Patients taking warfarin who are bleeding or need to undergo an invasive procedure before vitamin K could reverse the warfarin effect or who need only transient reversal of warfarin effect

Exclusion Criteria:

1. Patients aged < 18 years old

2. Receipt of any plasma product within 72 hours prior to the expected start of the index transfusion episode

3. Known intolerance to plasma or to any excipients (including citrate) in the investigational product (IP) formulation

4. Known history of any of the following:

   1. Hypersensitivity reaction to plasma or plasma-derived products
   2. Immunoglobulin A (IgA) deficiency with documented antibodies against IgA
   3. Congenital platelet disorder
   4. Congenital or acquired thrombophilia

5. Extracorporeal membrane oxygenation (ECMO) therapy at the time of screening

6. Undergoing or may require therapeutic plasma exchange (TPE) for thrombotic thrombocytopenic purpura (TTP)

7. Prisoner

8. Adults under legal guardianship or state custody, as defined by applicable local regulations

9. Trauma patients with the following:

   1. Traumatic cardiac arrest lasting > 5 minutes
   2. Glasgow Coma Score (GCS) of ≤ 8, with an exception for drug-induced lowered GCS
   3. Injury deemed nonsurvivable by trial team using established trauma assessment criteria
   4. Injury Severity Score (ISS) of 75 (when available)
   5. Known complete cervical spinal cord transection
   6. Third-degree burns of > 20% total body surface area

10. Female patients who are pregnant

11. Current or planned participation in any phase of another investigational trial during participation in this trial

12. Patients who self-report previous enrollment in the SAFE-PLASMA trial at any participating medical center

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Freeze-Dried Plasma (FDP); Participants enrolled during a center's assigned freeze-dried period receive EZPLAZ during the index transfusion episode, defined as the first 24 hours beginning with the first assigned plasma infusion. The treating physician determines the number of units required according to clinical need. After this period, either freeze-dried or conventional plasma may be administered if additional plasma is needed.	Biological: Freeze-Dried Plasma; Single-donor human plasma supplied in freeze-dried form and reconstituted with sterile water before transfusion. Administered by intravenous or intraosseous infusion as prescribed by the treating physician and in accordance with institutional transfusion policies. Dose is determined by clinical need.; Other Names: FDP; EZPLAZ; Lyophilized plasma
Active Comparator: Conventional Plasma; Participants enrolled during a center's assigned conventional plasma period receive conventional plasma during the index transfusion episode, defined as the first 24 hours beginning with the first assigned plasma infusion. The treating physician determines the number of units required according to clinical need. After this period, either freeze-dried or conventional plasma may be administered if additional plasma is needed.	Biological: Conventional Plasma; Conventional plasma products selected, prepared, and administered according to each institution's standard of care. The protocol does not restrict the types of conventional plasma used. The treating physician determines the dose based on clinical need.; Other Names: FFP; PF24; PF24RT24

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with a thrombotic/thromboembolic event, or death	Proportion of participants experiencing at least one thrombotic event, thromboembolic event, or death.	Within 7 days after the start of plasma transfusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with serious adverse events	Proportion of participants experiencing at least one serious adverse event, including acute and delayed reactions, evaluated at each specified time point.	Within 24 hours, 7 days, and 28 days after plasma infusion
Proportion of participants with treatment emergent adverse events	Proportion of participants experiencing at least one treatment emergent adverse event	Within 24 hours after the start of plasma infusion
Proportion of participants with unexpected adverse events	Proportion of participants experiencing at least one unexpected adverse event, as defined in the protocol	Within 28 days after plasma infusion
Proportion of participants with acute transfusion reactions	Proportions of participants experiencing any acute transfusion reactions and bloodstream infection	Within 24 hours post infusion
Proportion of participants who die	Proportion of participants who die after the start of the Index Transfusion Episode	Within 6 hours and 24 hours after the start of the Index Transfusion Episode
Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels	AST and ALT values obtained during routine clinical care, when available, summarized by laboratory parameter and time point	Pre-transfusion and 7 days post-transfusion
Creatinine Levels	Creatinine values obtained during routine clinical care, when available, summarized at each timepoint	Pre-transfusion and 7 days post-transfusion
Blood Urea Nitrogen (BUN)	BUN values obtained during routine clinical care, when available, summarized at each time point.	Pre-transfusion and 7 days post-transfusion
Volume of Blood Components and Crystalloid Fluids Administered at infusion	Total volume of each blood component and crystalloid fluid administered during the plasma infusion period, normalized by participant body weight	From start to complete of plasma infusion
Systolic and Diastolic Blood Pressure	Change in blood pressure, summarized separately for systolic and diastolic measurements. Mean change from baseline is calculated when paired measurements are available	Pre-infusion and 1-hour post-infusion
Heart Rate	Change in heart rate. Mean change from baseline is calculated when paired measurements are available, otherwise, mean observed values are reported.	Pre-infusion and 1 hour post-infusion
Respiratory Rate	Change in respiratory rate. Mean change from baseline is calculated when paired measurements are available, otherwise, mean observed values are reported.	Pre-infusion and 1 hour post-infusion
Body Temperature	Change in body temperature. Mean change from baseline is calculated when paired measurements are available, otherwise, mean observed values are reported.	Pre-infusion and 1 hour post-infusion
Oxygen Saturation	Change in oxygen saturation. Mean change from baseline is calculated when paired measurements are available, otherwise, mean observed values are reported.	Pre-infusion and 1 hour post-infusion

Collaborators and Investigators

• Sponsor: Teleflex
• Collaborators: Westat; United States Army Medical Materiel Development Activity

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2027
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): May 1, 2031

Study Registration Dates

• First Submitted: September 18, 2026
• First Submitted That Met QC Criteria: September 18, 2026
• First Posted (Actual): September 25, 2026

Study Record Updates

• Last Update Posted (Actual): September 30, 2026
• Last Update Submitted That Met QC Criteria: September 25, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: cluster randomized trial; Plasma transfusion; freeze-dried plasma; lyophilized plasma; EZPLAZ; conventional plasma; transfusion safety; SAFE-PLASMA
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Thromboembolism; formycin diphosphate
• Other Study ID Numbers: 2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No