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Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR)

This study has been completed.
Sponsor:
Collaborators:
Resuscitation Outcomes Consortium
Defence Research and Development Canada
Information provided by (Responsible Party):
John Holcomb, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT01545232
First received: February 29, 2012
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

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 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 Intervention Phase
Trauma
Biological: 1:1:1 Blood Transfusion Ratio
Biological: 1:1:2 Blood Transfusion Ratio
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pragmatic, Randomized Optimal Platelets and Plasma Ratios

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • 24-hour mortality [ Time Frame: First 24 hours after ED admission ] [ Designated as safety issue: Yes ]
  • 30-day mortality [ Time Frame: First 30 days after ED admission ] [ Designated as safety issue: Yes ]
  • Coagulation and inflammatory phenotypes at emergency department admission and over time. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hospital fee, ventilator free and ICU free days [ Time Frame: first 30 days after ED admission ] [ Designated as safety issue: No ]
  • Time to hemostasis, major surgical procedures, incidence of transfusion related serious adverse events. [ Time Frame: ED admission to hospital discharge or 30 days, whichever comes first ] [ Designated as safety issue: Yes ]
  • Amount of blood products given to hemostasis, amount of blood products given from hemostasis to 24 hours after ED admission [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  • Functional status at time of hospital discharge, initial hospital discharge status [ Time Frame: Hospital discharge or 30 days, whichever comes first ] [ Designated as safety issue: Yes ]

Enrollment: 680
Study Start Date: August 2012
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01545232

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35233
United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85721
United States, California
University of Southern California, Los Angeles
Los Angeles, California, United States, 90033
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Maryland
University of Maryland School of Medicine
Baltimore, Maryland, United States, 21201
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45221
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Tennessee
University of Tennessee Health Science Center
Memphis, Tennessee, United States, 38103
United States, Texas
University of Texas Health Science Center- Memorial Hermann Hospital
Houston, Texas, United States, 77030
United States, Washington
University of Washington- Harborview Medical Center
Seattle, Washington, United States, 98104
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
Sunnybrook Health Science Center
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Resuscitation Outcomes Consortium
Defence Research and Development Canada
Investigators
Study Director: John Holcomb, MD The University of Texas Health Science Center, Houston
  More Information

Additional Information:
No publications provided by The University of Texas Health Science Center, Houston

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: John Holcomb, Study Director, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT01545232     History of Changes
Other Study ID Numbers: HSC-GEN-11-0174, U01HL077863
Study First Received: February 29, 2012
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by 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

ClinicalTrials.gov processed this record on November 27, 2014