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

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ClinicalTrials.gov Identifier: NCT01545635
Recruitment Status : Terminated (The Interim analysis (100 patients) revealed a possible harm to patients randomised to the fresh frozen plasma (FFP) treatment arm.)
First Posted : March 7, 2012
Last Update Posted : March 23, 2016
Sponsor:
Information provided by (Responsible Party):
Univ.-Doz. Dr. Petra Innerhofer, Medical University Innsbruck

Tracking Information
First Submitted Date  ICMJE March 1, 2012
First Posted Date  ICMJE March 7, 2012
Last Update Posted Date March 23, 2016
Study Start Date  ICMJE March 2012
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 6, 2012)
Multiple Organ Failure (MOF) [ Time Frame: Variable until 24h on ICU at the end of the IMP-administration ]
Difference in the MOF as assessed by the Sequential Organ Failure Assessment score (SOFA) between treatment groups.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01545635 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma
Official Title  ICMJE RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma
Brief 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Major Trauma
Intervention  ICMJE
  • 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

  • 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
Study Arms  ICMJE
  • Active Comparator: Coagulation factor concentrates
    Intervention: Drug: Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrate
  • Active Comparator: Fresh Frozen Plasma
    Intervention: Drug: Fresh Frozen Plasma blood type 0, A, B and AB
Publications * Innerhofer P, Fries D, Mittermayr M, Innerhofer N, von Langen D, Hell T, Gruber G, Schmid S, Friesenecker B, Lorenz IH, Ströhle M, Rastner V, Trübsbach S, Raab H, Treml B, Wally D, Treichl B, Mayr A, Kranewitter C, Oswald E. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol. 2017 Jun;4(6):e258-e271. doi: 10.1016/S2352-3026(17)30077-7. Epub 2017 Apr 28. Erratum in: Lancet Haematol. 2017 Jun;4(6):e257.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 16, 2015)
100
Original Estimated Enrollment  ICMJE
 (submitted: March 6, 2012)
200
Actual Study Completion Date  ICMJE February 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01545635
Other Study ID Numbers  ICMJE RETIC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Univ.-Doz. Dr. Petra Innerhofer, Medical University Innsbruck
Study Sponsor  ICMJE Medical University Innsbruck
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Medical University Innsbruck
Verification Date March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP