RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma

Major Trauma Clinical Trial

Official title:

RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01545635
• Other study ID #: RETIC
• Status: Terminated
• Phase: Phase 3
• First received: March 1, 2012
• Last updated: March 22, 2016
• Start date: March 2012
• Est. completion date: February 2016

Study information

• Verified date: March 2016
• Source: Medical University Innsbruck
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health Care
• Study type: Interventional

Clinical Trial Summary

Severe traumatized patients (ISS > 15) admitted to emergency department (ED) University Hospital Innsbruck with obvious bleeding and/or who are at risk for significant hemorrhage will be screened by rotational thrombelastometry (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, 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 fresh frozen plasma (FFP),respectively.

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.

In cases unresponsive to comprehensive treatment or normal ROTEM combined with diffuse bleeding, other haemostatic medications can be administered (e.g rFVIIa, DDAVP, VWF/FVIII concentrate) as judged by the anesthetist in charge. The need and type of any rescue therapy will be documented and a ROTEM will be performed thereafter.

At admission to ICU (T0 ICU), 24h (T24 ICU) and 48h(T48 ICU) thereafter further study related blood samples are drawn (40mL each).

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 until 24h on ICU, patient's care is not influenced by the study and follows clinical routine.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Male and female subjects =/> 18 years and =/< 80 years

2. Major trauma (ISS > 15)

3. Clinical signs of ongoing bleeding or patients who are at risk for significant haemorrhage assessed and judged by the ED team in charge of patient

4. Presence of coagulopathy defined by ROTEM assays as follows,

• Patients with concomitant decreased fibrinogen polymerisation (ROTEM® FibTEM A10 of < 7 mm after 10 min)

• Patients with concomitant decreased coagulation factor levels (ROTEM® ExTEM CT of > 90 sec)

Exclusion Criteria:

1. Lethal injury

2. CPR on the scene,

3. Isolated brain injury, burn injury

4. Avalanche injury

5. Administration of FFP or coagulation factor concentrates before ED admission

6. Delayed (> 6hours after trauma) admittance to ED

7. Known use of oral anticoagulants, or platelet aggregation inhibitors within 5 days before injury

8. Known history of severe allergic reaction to plasma products

9. Known history of congenital hemostasis disturbance, IgA or Protein C deficiency

10. Patients with a history of thromboembolic events or heparin induced thrombocytopenia (HIT) type 2 within the last year

11. Patients with a body weight < 45kg and > 150kg

12. Patients that are known to be pregnant

13. Jehova's Witness

14. Known participation in another clinical trial

15. Patient with known refusal of a participation in this clinical trial

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Hemostatic Disorders
• Major Trauma
• Wounds and Injuries

Intervention

Drug:
• Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrate
Fibrinogen concentrate Dose: 50 mg/kg BW fibrinogen concentrate if FIBTEM A10<7mm Kind of application: Intravenously Frequency and rate of administration: Single-dose or repeated, each single vial (1g) over 5 min Prothrombin complex concentrate Dose: 20IE/kg BW PCC if EXTEM CT >90sec and FIBTEM A10>7mm Kind of application: Intravenously Frequency and rate of administration: Single-dose or repeated, each single dose over 10 min FXIII concentrate Dose: 20 IU/kg BW Fibrogammin® P will be administered with the second dose of fibrinogen concentrate (=100 mg/kg) and if FXIII decreases below 60% as detected by laboratory measurements. Kind of application: Intravenously Frequency and rate of administration: Single-dose or repeated, each single dose over 10 min
• Fresh Frozen Plasma blood type 0, A, B and AB
Fresh Frozen Plasma Dose: 15ml/kg BW if FibTEM A10 <7mm and/or ExTEM CT>90sec. Kind of application: Intravenously Frequency and rate of administration: Single-dose or repeated, each single U (200mL) over 5 min

Locations

Country	Name	City	State
Austria	Medical University Innsbruck / Department for Anesthesia and Intensive Care Medicine	Innsbruck	Tyrol

Sponsors (1)

Lead Sponsor	Collaborator
Medical University Innsbruck

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Multiple Organ Failure (MOF)	Difference in the MOF as assessed by the Sequential Organ Failure Assessment score (SOFA) between treatment groups.	Variable until 24h on ICU at the end of the IMP-administration	No