Pilot Study 03 :: RETIC

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Reversal of Trauma Induced Coagulopathy using Coagulation factor concentrates or Fresh frozen Plasma.
Prospective, open-label, randomized, parallel-group, monocentric Clinical Trial

Primary Objective
The aim of the study is to assess the difference in incidence of multi organ failure (MOF) after treatment of TIC with Fresh frozen plasma (FFP) or Coagulation factor concentrates (CFC).

Primary Endpoint
The primary endpoint of the study is the difference in incidence of MOF between the CFC and FFP groups.

Study Start: March 2012

End of Study: March 2014

Number of Patients
200 (2x100) evaluable patients

Duration of Patient Participation
• Treatment: Emergency Department (ED) until 24h on ICU
• Follow-Up Period “Medical Monitoring”: until day 30 after admission

Investigational Medicinal Product:
Coagulation factor concentrates (CFC):
• Fibrinogen concentrate, Haemocomplettan® P 1g, CSL Behring, Marburg, Germany (1.0g per 50 mL).
• Prothrombin complex concentrate (PCC), Beriplex® P/N 500, CSL Behring, Marburg, Germany .
• FXIII concentrate: Fibrogammin® P 250 E and P 1250 E, CSL Behring, Marburg, Germany
Fresh Frozen Plasma:
• Octaplas SD blood type 0, A, B and AB® Octapharma Pharmazeutika, Wien Number of Patients 200 (2x100) evaluable patients
   Duration of Patient Participation
• Treatment: Emergency Department (ED) until 24h on ICU
• Follow-Up Period “Medical Monitoring”: until day 30 after admission

I.1. Male and female subjects ≥ 18 years and < 80 years,
I.2. Major trauma (ISS>15),
I.3. Clinical signs of ongoing bleeding or patients who are at risk of significant haemorrhage assessed and judged by the ED team in charge of patient
I.4. Presence of coagulopathy defined by ROTEM assays as follows,
- Patients with concomitant decreased fibrinogen polymerisation as measured with ROTEM® FibTEM A10 of < 7 mm after 10 min
- Patients with concomitant decreased coagulation factor levels as measured with ROTEM® ExTEM CT of > 90 sec

E.1. Lethal injury
E.2. CPR on the scene,
E.3. Isolated brain injury, burn injury
E.4. Avalanche injury
E.5. Administration of FFP or coagulation factor concentrates before ED admission
E.6. Delayed (>6hours after trauma) admittance to ED
E.7. Known use of oral anticoagulants, or platelet aggregation inhibitors within 5 days before injury
E.8. Known history of severe allergic reaction to plasma products
E.9. Known history of congenital hemostasis disturbance, IgA or Protein C deficiency
E.10. Patients with a history of thromboembolic events (myocardial infarction, unstable angina pectoris, stroke, deep venous thrombosis, pulmonary embolism) or heparin induced thrombocytopenia (HIT) type 2 within the prior 12 month
E.11. Patients with a body weight <45kg and >150kg
E.12. Patients that are known to be pregnant

Severe traumatized patients (ISS >15) admitted to ED University Hospital Innsbruck with obvious bleeding and/or who are at risk for significant hemorrhage will be screened by ROTEM assays during ED treatment and subsequent surgical/radiological interventions for having coagulopathy (T0).
If a patient meets the inclusion criteria (T1) and is recruited for the study (inclusion- and exclusion criteria: see above), a first study related blood sample (40mL) will be drawn, and data collected.
Subsequently, 100 patients will be randomized to receive Fibrinogen concentrate and/or Prothrombin complex concentrate and/or FXIII concentrate for reversal of coagulopathy, while the other 100 patients will receive FFP 15ml/kg BW ,respectively.
The study specific coagulation management using CFC or FFP starts with randomization (T1) and is continued during the first 24h on ICU (T24 ICU). Depending on the individual demands of the patient one single (T1) or several treatment episodes (T2-Txy) will occur .
Study drug administration is aimed to correct each single occurring coagulopathic bleeding episode as assessed by FibTEM and ExTEM.
In both groups ROTEM (ExTEM, FibTEM) will be performed 20 min after study drug administration to ensure sufficient reversal of coagulopathy. If coagulopathy persists, the dose of study drug will be repeated and efficacy checked thereafter.
Treatment failure will be registered if bleeding persists and ROTEM parameters do not improve after two times dosages of study drug. In these cases haemostatic rescue therapy will be administered. CFC (fibrinogen concentrate and/or PCC, and/or FXIII concentrate) will be administered to patients randomized to receive FFP and FFP will be administered to patients of the CFC group.
At admission to ICU (T0 ICU), 24h (T24 ICU) and 48h(T48 ICU) thereafter further study related blood samples are drawn.
The indications for transfusion of red blood cells or platelets, administration of antifibrinolytics, treatment of acidosis, hypothermia, hypocalcemia and volume replacement are similar for both groups and treatment is performed according to clinical routine.
Besides coagulation management during ED treatment