Finnish Prehospital Whole Blood Study

Study Overview
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Brief Summary
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Up-to-date evidence suggests that blood transfusion initiated as early as possible reduces the likelihood of death from hemorrhagic shock, and the sooner replacement therapy with blood products is initiated, the greater the effect on mortality. Typically, the patient is transfused with one to two units of O RhD (Rh blood group D antigen) negative packed red blood cells (PRBC). Hemostasis accelerating medicines (dry plasma, tranexamic acid, calcium, fibrinogen) as well as crystalloids are also often given. Finnish Red Cross Blood Service is validating cold stored, 0 RhD positive, male donor, leucoreduced, platelet sparing, low blood group ABO antibody titer whole blood product (LTOWB). For this prospective, open, non-randomized clinical study LTOWB will be used in three prehospital emergency medical services that currently use most of prehospital blood products in Finland, while other participating prehospital emergency medical service bases provide controls. Blood transfusions will be given for clinical indication only. The primary goal is to introduce LTOWB and to analyze its feasibility in Finnish prehospital emergency medical service. Study also aims to prove safety of LTOWB, and to analyze coagulation properties of LTOWB compared to currently prehospitally used PRBC transfusions.

Detailed Description
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Up-to-date evidence suggests that blood transfusion initiated as early as possible reduces the likelihood of death from hemorrhagic shock, and the sooner replacement therapy with blood products is initiated, the greater the effect on mortality. Since the mid-2010s, prehospital emergency medical services in Finland have used blood transfusions. Typically, the patient is transfused with one to two units of O RhD (Rh blood group D antigen) negative packed red blood cells (PRBC). Hemostasis accelerating medicines (dry plasma, tranexamic acid, calcium, fibrinogen) as well as crystalloids are also often given during pre-hospital emergency treatment. Platelets are not used prehospitally in Finland due to logistic reasons. The international trend has been the re-emergence of whole blood as the primary replacement product for acute bleeding. Finnish Red Cross Blood Service is validating cold stored, 0 RhD positive, male donor, leucoreduced, platelet sparing, low blood group ABO antibody titer whole blood product (LTOWB). For this prospective, open, non-randomized clinical study LTOWB will be used in three prehospital emergency medical services that currently use most of prehospital blood products in Finland (HUS area, Pirkanmaa area and Päijät-Häme area). Other participating prehospital emergency medical service bases provide controls. Blood transfusions will be given for clinical indication only. The primary goal is to introduce LTOWB and to analyze its feasibility in Finnish prehospital emergency medical service. Study also aims to prove safety of LTOWB, and to analyze coagulation properties of LTOWB and its effects on endothelial injury and inflammation compared to currently prehospitally used PRBC transfusions. The primary endpoint of the clinical study is the number of patients having severe coagulopathy (measured as INR of = 1.5) at hospital arrival. The secondary outcomes in order of precedence are: Number of patients having coagulopathy at hospital arrival (INR >1.2), time at the scene of transfusion capable unit , need for massive transfusion protocol at hospital, discharge from primary hospital, discharge from intensive care unit, number of patients with acute lung injury according to Berlin definition, in-hospital mortality, 24 hour mortality, any serious adverse effect within 30 days, any adverse effect excluding anti-D formation of D-negative patients within 30 days. Study begins at first quarter of 2022 and recruiting for clinical part of the study continues three years. All adult (=18 years of age) patients who receive prehospital LTOWB or PRBC transfusion during study period in contributing prehospital emergency medical services will be asked to participate using delayed informed consent procedure from patient, or their next of kin if patient is unable due to his/her condition. Consent will not be asked from next of kin and no blood samples for study will be collected, if patient dies before any contact. In addition to clinical data, a survey that analyses the emergency care team-members' experiences of transfusion events at prehospital setting will be conducted, and prehospital time logs will be compared between the LTOWB and control groups. In addition, separate blood samples will be collected for coagulation, endothelial injury and inflammatory response analyses from subsample of the patients.

Official Title
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Finnish Prehospital Whole Blood Study

Conditions
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Hemorrhage

Intervention / Treatment
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* Other: Packed red cell transfusion
* Other: Whole blood transfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -All adult patients that have been given a blood transfusion during prehospital emergency care Exclusion Criteria: - Age less than 18 years

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Non-randomized, open label design. 3 centers use whole blood while others use packed red cells as pre-hospital transfusion therapy. Only study related intervention is additional blood samples from sub-group of patients for in vivo coagulation studies.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Packed red blood cell<br>control | Other: Packed red cell transfusion<br>* Type O RhD negative packed red cell transfusion during prehospital emergency care<br>|
| Experimental: Low titer whole blood<br>case | Other: Whole blood transfusion<br>* Type O RhD positive, low titer whole blood transfusion during prehospital emergency care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe coagulopathy | Number of patients having severe coagulopathy (measured as INR of = 1.5) | within 30 minutes upon arrival to the hospital | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coagulopathy | Number of patients having coagulopathy (INR >1.2) | within 30 minutes upon arrival to the hospital | 
| Time spend at the scene | Time (min) from arrival of transfusion capable unit at the scene to depart of the patient to the hospital. | 1-500 minutes | 
| Number of patients needing massive transfusion protocol | Need for massive transfusion protocol at hospital | During first 24 hours after arrival to the hospital | 
| Time treated at the hospital | Time (days) patient is treated at the hospital capable of providing curative treatment to the patients medical condition. Data gathered from patient records (admission to ICU and discharge from ICU date) | From day 0 (arrival to the hospital) to the date of discharge from the hospital or date of death from any cause, whichever came first, assessed up to 36 months. | 
| Time treated at the intensive care unit | Time (days) patient is treated at the intensive care unit during first ICU episode. Data gathered from patient records (admission to ICU and discharge from ICU date) | From day 0 (arrival to ICU) to the date of discharge/removal to the ward or date of death, whichever came first, assessed up to 36 months. | 
| Number of patients with acute lung injury | Number of patients with acute lung injury according to Berlin definition | From day 0 (arrival to the hospital) to the date of discharge from the hospital or date of death, whichever came first, assessed up to 36 months | 
| In-hospital mortality | Mortality during initial hospitalization period | From day 0 (arrival to the hospital) to the date of discharge from the hospital or or date of death, whichever came first, assessed up to 36 months | 
| 24 hour mortality | Any mortality during first 24 hours from event | 24 hours from the event | 
| Serious adverse effects | Any serious adverse effect within 30 days | 30 days from the event | 
| Adverse effects | Any adverse effect excluding anti-D formation of D-negative patients within 30 days. | 30 days from the event | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transfusion, Prehospital emergency care