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

This study is currently recruiting participants.
Verified June 2012 by Medical University Innsbruck
Sponsor:
Information provided by (Responsible Party):
Univ.-Doz. Dr. Petra Innerhofer, Medical University Innsbruck
ClinicalTrials.gov Identifier:
NCT01545635
First received: March 1, 2012
Last updated: June 28, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Major Trauma
Drug: Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrate
Drug: Fresh Frozen Plasma blood type 0, A, B and AB
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma

Resource links provided by NLM:


Further study details as provided by Medical University Innsbruck:

Primary Outcome Measures:
  • Multiple Organ Failure (MOF) [ Time Frame: Variable until 24h on ICU at the end of the IMP-administration ] [ Designated as safety issue: No ]
    Difference in the MOF as assessed by the Sequential Organ Failure Assessment score (SOFA) between treatment groups.


Estimated Enrollment: 200
Study Start Date: March 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Coagulation factor concentrates 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

Active Comparator: Fresh Frozen Plasma Drug: 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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01545635

Contacts
Contact: Petra Innerhofer, MD 0043512504 ext 80407 petra.innerhofer@uki.at
Contact: Markus Mittermayr, MD 0043512504 ext 80485 markus.mittermayr@uki.at

Locations
Austria
Medical University Innsbruck / Department for Anesthesia and Intensive Care Medicine Recruiting
Innsbruck, Tyrol, Austria, 6020
Contact: Petra Innerhofer, MD    0043512504 ext 80407    petra.innerhofer@uki.at   
Contact: Markus Mittermayr, MD    0043512504 ext 80485    markus.mittermayr@uki.at   
Principal Investigator: Petra Innerhofer, MD         
Sponsors and Collaborators
Medical University Innsbruck
  More Information

No publications provided

Responsible Party: Univ.-Doz. Dr. Petra Innerhofer, Principal Investigator, Medical University Innsbruck
ClinicalTrials.gov Identifier: NCT01545635     History of Changes
Other Study ID Numbers: RETIC
Study First Received: March 1, 2012
Last Updated: June 28, 2012
Health Authority: Austria: Federal Office for Safety in Health Care

Keywords provided by Medical University Innsbruck:
Major trauma
Injury Severity Score
ISS > 15
clinical signs
risk of blood loss
coagulopathy
rotational thrombelastometry
ROTEM

Additional relevant MeSH terms:
Blood Coagulation Disorders
Hemostatic Disorders
Wounds and Injuries
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Thrombin
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014