PROPPR: Pragmatic, Randomized Optimal Platelet and Plasma Ratios

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Completed
• CT.gov ID: NCT01545232
• Collaborator: United States Department of Defense (U.S. Fed), National Heart, Lung, and Blood Institute (NHLBI) (NIH), Resuscitation Outcomes Consortium (Other), Defence Research and Development Canada (Industry)
• Enrollment: 680
• Locations: 12
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 56.7
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR)is a Phase III trial designed to evaluate the difference in 24-hour and 30-day mortality among subjects predicted to receive massive transfusion ([MT] (defined as receiving 10 units or more red blood cells (RBCs) within the first 24 hours). The goal of PROPPR is to improve the basis on which clinicians make decisions about transfusion protocols for massively bleeding patients.

PROPPR is a Resuscitation Outcomes Consortium (ROC) Protocol. ROC is funded by the National Heart, Lung, and Blood Institute (NHLBI), the United States' Department of Defense (DoD) and the Defence Research and Development Canada. PROPPR will be conducted as a Phase III trial at Level I Adult Trauma Centers in North America.

Condition or Disease	Intervention/Treatment	Phase
Trauma	Biological: 1:1:1 Blood Transfusion Ratio; Biological: 1:1:2 Blood Transfusion Ratio	Phase 3

Detailed Description

Background: Multiple observational studies have reported that blood product component ratios (i.e., plasma:platelets:RBCs) that approach the 1:1:1 ratio, found in fresh whole blood, are associated with significant decreases in truncal hemorrhagic death and in overall 24-hour and 30-day mortality among injured patients. The rationale for the 1:1:1 ratio is that the closer a transfusion regimen approximates whole blood, the faster hemostasis will be achieved with minimum risk of coagulopathy. The current DoD guideline specifies the use of 1:1:1, and this practice is followed on almost all combat casualties. In other observational studies, leading centers have reported good outcomes across a range of different blood product ratios. For example, a 1:2 plasma:RBC ratio is used with little guidance regarding platelets. The proposed randomized trial is intended to resolve debate and uncertainty regarding optimum blood product ratios.

Study Design: Randomized, two-group, controlled Phase III trial with a Vanguard stage. Equal random allocation to treatment using stratified, permuted blocks with randomly chosen block sizes and stratification by site.

Objective: To conduct a Phase III multi-site, randomized trial in subjects predicted to have a massive transfusion, comparing the efficacy and safety of 1:1:1 transfusion ratios of plasma and platelets to red blood cells (the closest approximation to reconstituted whole blood) with the 1:1:2 ratio. The co-primary outcomes will be 24-hour and 30-day mortality. The PROPPR Trial will be conducted with exception from informed consent (EFIC). Additionally, laboratory data from the trial will add to the understanding of trauma induced coagulopathy (TIC) and inflammation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 680 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pragmatic, Randomized Optimal Platelet and Plasma Ratios
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1:1:1 Blood Transfusion Ratio	Biological: 1:1:1 Blood Transfusion Ratio; Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.
Active Comparator: 1:1:2 Blood Transfusion Ratio	Biological: 1:1:2 Blood Transfusion Ratio; Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.

Outcome Measures

Primary Outcome Measures

1. 24-hour Mortality [First 24 hours after ED admission]

2. 30-day Mortality [First 30 days after ED admission]

3. Coagulation as Indicated by Number of Participants With Reported Venous Thrombolic Events (VTE) [From time of ED admission, for up to 72 hours]

   Blood samples were collected at time of ED admission and over time to determine the incidence of reported venous thrombolic events (VTE).

Secondary Outcome Measures

1. Hospital Free Days [first 30 days after ED admission]

2. Time to Hemostasis [ED admission to hospital discharge or 30 days, whichever comes first]

   Time to hemostasis refers to the time that the subject achieved hemorrhage control (anatomic hemostasis and resuscitation complete)following emergency department (ED) arrival.

3. Amount of Randomized Blood Products Given to Hemostasis [24 hours from randomization]

4. Functional Status at Time of Hospital Discharge [Hospital discharge or 30 days, whichever comes first]

   The Glasgow Outcome Extended Score (GOSE) is a tool used to measure recovery following brain injury and assists with prediction of long-term rehabilitation. The 8 scoring categories are death, vegetative state, lower severe disability, upper severe disability, lower moderate disability, upper moderate disability, lower good recovery and upper good recovery. A higher GOSE score correlates with better outcome.

5. Incidence of Primary Surgical Procedure [ED admission to hospital discharge or 30 days, whichever comes first]

6. Incidence of Transfusion Related Serious Adverse Events [ED admission to hospital discharge or 30 days, whichever comes first]

7. Initial Hospital Discharge Status [Hospital discharge or 30 days, whichever comes first]

8. Ventilator Free Days [first 30 days after ED admission]

9. ICU Free Days [first 30 days after ED admission]

10. Amount of Blood Products Given From Hemostasis to 24 Hours After ED Admission [24 hours after ED admission]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects who require the highest trauma team activation at each participating center,

• Estimated age of 15 years or older or greater than/equal to weight of 50 kg if age unknown,

• Received directly from the injury scene,

• Initiated transfusion of at least one unit of blood component within the first hour of arrival or during prehospital transport, and

• Predicted to receive a MT by exceeding the threshold score of either the Assessment of Blood Consumption (ABC) score or the attending trauma physician's judgment criteria

Exclusion Criteria:

• Received care (as defined as receiving a life saving intervention) from an outside hospital or healthcare facility (Procedures and care given at an outside health facility cannot be documented or controlled resulting in a high variability of standards of care and clinical outcomes.)

• Moribund patient with devastating injuries and expected to die within one hour of Emergency Department (ED) admission

• Prisoners, defined as those who have been directly admitted from a correctional facility

• Patients requiring an emergency thoracotomy

• Children under the age of 15 years or under 50 kg body weight if age unknown

• Known pregnancy in the ED

• Greater than 20% total body surface area (TBSA) burns

• Suspected inhalation injury

• Received greater than five consecutive minutes of cardiopulmonary resuscitation (CPR with chest compressions) in the pre-arrival or ED setting

• Known Do Not Resuscitate (DNR) prior to randomization

• Enrolled in a concurrent, ongoing interventional, randomized clinical trial

• Patients who have activated the "opt-out" process or patients/legally authorized representatives that refuse blood products on arrival to ED.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35233
2	University of Arizona	Tucson	Arizona	United States	85721
3	University of Southern California, Los Angeles	Los Angeles	California	United States	90033
4	University of California, San Francisco	San Francisco	California	United States	94143
5	University of Maryland School of Medicine	Baltimore	Maryland	United States	21201
6	University of Cincinnati	Cincinnati	Ohio	United States	45221
7	Oregon Health and Science University	Portland	Oregon	United States	97239
8	University of Tennessee Health Science Center	Memphis	Tennessee	United States	38103
9	University of Texas Health Science Center- Memorial Hermann Hospital	Houston	Texas	United States	77030
10	University of Washington- Harborview Medical Center	Seattle	Washington	United States	98104
11	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
12	Sunnybrook Health Science Center	Toronto	Ontario	Canada	M4N 3M5

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston
• United States Department of Defense
• National Heart, Lung, and Blood Institute (NHLBI)
• Resuscitation Outcomes Consortium
• Defence Research and Development Canada

Investigators

• Study Director: John Holcomb, MD, The University of Texas Health Science Center, Houston

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John Holcomb, Study Director, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT01545232
• Other Study ID Numbers: HSC-GEN-11-0174; U01HL077863
• First Posted: Mar 6, 2012
• Last Update Posted: Feb 8, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by John Holcomb, Study Director, The University of Texas Health Science Center, Houston: Massive Transfusion; Trauma; Coagulopathy; Trauma Induced Coagulopathy; Plasma; Platelets; Red Blood Cells; Mortality; Wounds and Injuries; Shock, Hemorrhagic; Shock; Pathologic Processes; Hemorrhage; Hemostatics; Coagulation; Transfusion-related acute lung injury (TRALI); Inflammation
• Additional relevant MeSH terms: Wounds and Injuries

Study Results

Participant Flow

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Period Title: Overall Study
STARTED	338	342
COMPLETED	338	342
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio	Total
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.	Total of all reporting groups
Overall Participants	338	342	680
Age, Customized (participants) [Number]
Number [participants]	338 100%	342 100%	680 100%
Sex: Female, Male (Count of Participants)
Female	75 22.2%	59 17.3%	134 19.7%
Male	263 77.8%	283 82.7%	546 80.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	61 18%	59 17.3%	120 17.6%
Not Hispanic or Latino	277 82%	283 82.7%	560 82.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	6 1.8%	2 0.6%	8 1.2%
Asian	21 6.2%	8 2.3%	29 4.3%
Native Hawaiian or Other Pacific Islander	3 0.9%	1 0.3%	4 0.6%
Black or African American	93 27.5%	93 27.2%	186 27.4%
White	210 62.1%	224 65.5%	434 63.8%
More than one race	2 0.6%	0 0%	2 0.3%
Unknown or Not Reported	3 0.9%	14 4.1%	17 2.5%

Outcome Measures

1. Primary Outcome

Title	24-hour Mortality
Time Frame	First 24 hours after ED admission

Outcome Measure Data

Analysis Population Description

Number of subjects who were randomized to each group

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	338	342
Number [participants]	43 12.7%	58 17%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1:1:1 Blood Transfusion Ratio, 1:1:2 Blood Transfusion Ratio
	Comments	Initial sample size (580) planned to detect a clinically meaningful 10% difference in 24-hour mortality (11% vs. 21%) supported by prior data. Data Safety Monitoring Board (DSMB) increased sample size to 680 according to trial's adaptive design. With 680 pts. & given the final observed mortality proportions in 1:1:1 group, PROPPR had 95% power to detect the pre-specified 10% difference at 24 hours if such differences existed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Mantel Haenszel
	Comments	The critical level for significance (p<0.044) was adjusted for two interim analyses, and all tests were conducted using two-sided tests.
Method of Estimation	Estimation Parameter	Adjusted Relative Risk
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	30-day Mortality
Time Frame	First 30 days after ED admission

Outcome Measure Data

Analysis Population Description

Number of subjects enrolled into each group.

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	338	342
Number [participants]	75 22.2%	89 26%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1:1:1 Blood Transfusion Ratio, 1:1:2 Blood Transfusion Ratio
	Comments	Initial sample size of 580 planned to detect clinically meaningful a 12% difference in 30-day mortality (23% vs. 35%),supported by prior data. DSMB increased sample size to 680 according to trial's adaptive design. With 680 patients & given final observed mortality proportions in the 1:1:1 group, PROPPR had 92% power to detect the pre-specified 12% difference at 30 days, if such differences existed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Mantel Haenszel
	Comments	The critical level for significance (p<0.044) was adjusted for two interim analyses, and all tests were conducted using two-sided tests.
Method of Estimation	Estimation Parameter	Adjusted Relative Risk
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Coagulation as Indicated by Number of Participants With Reported Venous Thrombolic Events (VTE)
Description	Blood samples were collected at time of ED admission and over time to determine the incidence of reported venous thrombolic events (VTE).
Time Frame	From time of ED admission, for up to 72 hours

Outcome Measure Data

Analysis Population Description

Number of subjects who were randomized to each group

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio.
Measure Participants	338	342
Number [participants]	45 13.3%	42 12.3%

4. Secondary Outcome

Title	Hospital Free Days
Time Frame	first 30 days after ED admission

Outcome Measure Data

Analysis Population Description

Number of hospital free days for each group.

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	338	342
Median (Inter-Quartile Range) [days]	1	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1:1:1 Blood Transfusion Ratio, 1:1:2 Blood Transfusion Ratio
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	van Elteren's test for medians
	Comments

5. Secondary Outcome

Title	Time to Hemostasis
Description	Time to hemostasis refers to the time that the subject achieved hemorrhage control (anatomic hemostasis and resuscitation complete)following emergency department (ED) arrival.
Time Frame	ED admission to hospital discharge or 30 days, whichever comes first

Outcome Measure Data

Analysis Population Description

Time to anatomic hemostasis

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	338	342
Median (Inter-Quartile Range) [minutes]	105	100

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1:1:1 Blood Transfusion Ratio, 1:1:2 Blood Transfusion Ratio
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	van Elteren's test for medians
	Comments

6. Secondary Outcome

Title	Amount of Randomized Blood Products Given to Hemostasis
Time Frame	24 hours from randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	338	342
Median (Inter-Quartile Range) [units of blood products]	16	15

7. Secondary Outcome

Title	Functional Status at Time of Hospital Discharge
Description	The Glasgow Outcome Extended Score (GOSE) is a tool used to measure recovery following brain injury and assists with prediction of long-term rehabilitation. The 8 scoring categories are death, vegetative state, lower severe disability, upper severe disability, lower moderate disability, upper moderate disability, lower good recovery and upper good recovery. A higher GOSE score correlates with better outcome.
Time Frame	Hospital discharge or 30 days, whichever comes first

Outcome Measure Data

Analysis Population Description

Glasgow Outcome Extended Score (GOSE) Score on discharged patients who had a head injury (Abbreviated Injury Score (AIS) > 1) ranging from 1 to 8. The AIS is a coding scale to classify the injury severity. A score is created for each body region, type of anatomic structure (i.e. whole area, vessels,organs), and severity(minor to maximum).

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	30	28
Median (Inter-Quartile Range) [units on the GOSE scale]	4	4.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1:1:1 Blood Transfusion Ratio, 1:1:2 Blood Transfusion Ratio
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	van Elteren's test for medians
	Comments

8. Secondary Outcome

Title	Incidence of Primary Surgical Procedure
Time Frame	ED admission to hospital discharge or 30 days, whichever comes first

Outcome Measure Data

Analysis Population Description

Incidence of primary surgical procedure

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	338	342
Number [participants]	290 85.8%	284 83%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1:1:1 Blood Transfusion Ratio, 1:1:2 Blood Transfusion Ratio
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95%; -2.8 to 8.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Incidence of Transfusion Related Serious Adverse Events
Time Frame	ED admission to hospital discharge or 30 days, whichever comes first

Outcome Measure Data

Analysis Population Description

Incidence of transfusion related serious adverse events-Reportable to FDA

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	338	342
Number [participants]	1 0.3%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1:1:1 Blood Transfusion Ratio, 1:1:2 Blood Transfusion Ratio
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Initial Hospital Discharge Status
Time Frame	Hospital discharge or 30 days, whichever comes first

Outcome Measure Data

Analysis Population Description

Disposition of subject at time of hospital discharge

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	338	342
Home	118 34.9%	105 30.7%
Remained hospitalized at 30 days	82 24.3%	77 22.5%
Other	59 17.5%	71 20.8%
Morgue	75 22.2%	89 26%
Unknown	4 1.2%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1:1:1 Blood Transfusion Ratio, 1:1:2 Blood Transfusion Ratio
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	generalized logit model regression
	Comments

11. Secondary Outcome

Title	Ventilator Free Days
Time Frame	first 30 days after ED admission

Outcome Measure Data

Analysis Population Description

Number of ventilator free days for each group.

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	338	342
Median (Inter-Quartile Range) [days]	8	7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1:1:1 Blood Transfusion Ratio, 1:1:2 Blood Transfusion Ratio
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	van Elteren's test for medians
	Comments

12. Secondary Outcome

Title	ICU Free Days
Time Frame	first 30 days after ED admission

Outcome Measure Data

Analysis Population Description

Number of ICU free days for each group.

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	338	342
Median (Inter-Quartile Range) [days]	5	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1:1:1 Blood Transfusion Ratio, 1:1:2 Blood Transfusion Ratio
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	van Elteren's test for medians
	Comments

13. Secondary Outcome

Title	Amount of Blood Products Given From Hemostasis to 24 Hours After ED Admission
Time Frame	24 hours after ED admission

Outcome Measure Data

Analysis Population Description

Unit of measure for outcome measures below is median number of blood product units that given in each group (1:1:1 or 1:1:2) from time initial hemostasis was complete (PROPPR randomized study products stopped) up to 24 hours following ED admission. Number of participants is based on those who survived up to 24 hours, not participants randomized.

Arm/Group Title	1:1:1 Blood Transfusion Ratio	1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.	1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
Measure Participants	316	305
Median (Inter-Quartile Range) [units of blood products]	1	2

Adverse Events

Time Frame	up to 30 days following ED admission
Arm/Group Title	1:1:1 Blood Transfusion Ratio		1:1:2 Blood Transfusion Ratio
Arm/Group Description	1:1:1 Blood Transfusion Ratio: Group 1 will be randomized to receive the 1:1:1 ratio of plasma:platelets:RBC. Blood bank will prepare the initial container containing 6 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC; the blood bank will send the initial and all subsequent containers until notified of the discontinuation of the PROPPR transfusion protocol.		1:1:2 Blood Transfusion Ratio: Group 2 will be randomized to receive the 1:1:2 ratio of plasma:platelets:RBC. The blood bank will prepare the initial container containing 3 units plasma, 0 units platelets and 6 units RBC, a second container containing 3 units plasma, 1 unit platelets (a pool of 6 units on average) and 6 units RBC, and the blood bank will send this sequence of 2 containers repeatedly, until notified of the discontinuation of the PROPPR transfusion protocol.
All Cause Mortality
	1:1:1 Blood Transfusion Ratio		1:1:2 Blood Transfusion Ratio
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1:1:1 Blood Transfusion Ratio		1:1:2 Blood Transfusion Ratio
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/338 (0.6%)		4/342 (1.2%)
Cardiac disorders
Transfusion-associated circulatory overload	1/338 (0.3%)	1	0/342 (0%)	0
Metabolism and nutrition disorders
Hypernatremia associated with hypertonic saline use	1/338 (0.3%)	1	4/342 (1.2%)	4
Other (Not Including Serious) Adverse Events
	1:1:1 Blood Transfusion Ratio		1:1:2 Blood Transfusion Ratio
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	297/338 (87.9%)		310/342 (90.6%)
Cardiac disorders
Cardiac arrest	23/338 (6.8%)	25	27/342 (7.9%)	30
Myocardial Infarction	0/338 (0%)	0	2/342 (0.6%)	2
General disorders
Systemic inflammatory response syndrome	231/338 (68.3%)	265	216/342 (63.2%)	239
Abdominal Complication	24/338 (7.1%)	29	22/342 (6.4%)	23
Multiple Organ Failure	20/338 (5.9%)	24	15/342 (4.4%)	18
Additional bleeding after hemostasis requiring intervention	13/338 (3.8%)	13	16/342 (4.7%)	18
Abdominal Compartment syndrome	3/338 (0.9%)	3	3/342 (0.9%)	3
Transfusion-related allergic reaction	2/338 (0.6%)	2	1/342 (0.3%)	1
Immune system disorders
Delayed serological transfusion reaction	2/338 (0.6%)	2	0/342 (0%)	0
Febrile nonhemolytic transfusion reaction	1/338 (0.3%)	1	1/342 (0.3%)	1
Infections and infestations
Sepsis	99/338 (29.3%)	110	91/342 (26.6%)	102
Infection	98/338 (29%)	155	106/342 (31%)	146
Ventilator-associated pneumonia	62/338 (18.3%)	70	58/342 (17%)	65
Metabolism and nutrition disorders
Transfusion-related metabolic complications	53/338 (15.7%)	53	59/342 (17.3%)	60
Nervous system disorders
Stroke	8/338 (2.4%)	9	11/342 (3.2%)	11
Renal and urinary disorders
Acute Kidney Injury	74/338 (21.9%)	87	85/342 (24.9%)	93
Respiratory, thoracic and mediastinal disorders
Acute Lung Injury	47/338 (13.9%)	56	57/342 (16.7%)	66
Acute Respiratory Distress Syndrome	46/338 (13.6%)	55	48/342 (14%)	57
Symptomatic pulmonary embolism	14/338 (4.1%)	14	13/342 (3.8%)	13
Asymptomatic pulmonary embolism	11/338 (3.3%)	11	11/342 (3.2%)	11
Vascular disorders
Deep Vein Thrombosis	25/338 (7.4%)	28	24/342 (7%)	24

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.