Major TraumaPhase 3NCT01545635

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

A Phase 3 study testing Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrate and Fresh Frozen Plasma blood type 0, A, B and AB in people with Major Trauma, run by Medical University Innsbruck at 1 site in Austria.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Major Trauma
What is being tested?: Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrate and Fresh Frozen Plasma blood type 0, A, B and AB
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 100 participants
Where: 1 siteAustria
Study dates: Mar 2012to Feb 2016
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female subjects =/> 18 years and =/< 80 years
Major trauma (ISS > 15)
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
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)

Who cannot join

Lethal injury
CPR on the scene,
Isolated brain injury, burn injury
Avalanche injury
Administration of FFP or coagulation factor concentrates before ED admission
Delayed (> 6hours after trauma) admittance to ED

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Known use of oral anticoagulants, or platelet aggregation inhibitors within 5 days before injury
Known history of severe allergic reaction to plasma products
Known history of congenital hemostasis disturbance, IgA or Protein C deficiency
Patients with a history of thromboembolic events or heparin induced thrombocytopenia (HIT) type 2 within the last year
Patients with a body weight < 45kg and > 150kg
Patients that are known to be pregnant
Jehova's Witness
Known participation in another clinical trial
Patient with known refusal of a participation in this clinical trial

Trial locations and contacts

1 site in 1 country.

Austria1 site

Medical University Innsbruck / Department for Anesthesia and Intensive Care Medicine
Innsbruck, Tyrol, 6020

Other trials in Austria

About this study

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.

Conditions: Major Trauma
Being tested: Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrate, Fresh Frozen Plasma blood type 0, A, B and AB
Keywords: Major trauma, Injury Severity Score, ISS > 15, clinical signs, risk of blood loss, coagulopathy, rotational thrombelastometry, ROTEM
Medical subject headings: Signs and Symptoms, Hemostatic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrateDrug
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 ABDrug
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 groups in NCT01545635
Study group	Role	What they receive
Coagulation factor concentrates	Active comparator	Not described Receives: Drug: Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrate
Fresh Frozen Plasma	Active comparator	Not described Receives: Drug: Fresh Frozen Plasma blood type 0, A, B and AB

What is being measured

The primary outcome is the main question the study is designed to answer.

Multiple Organ Failure (MOF)
Difference in the MOF as assessed by the Sequential Organ Failure Assessment score (SOFA) between treatment groups.
Measured: Variable until 24h on ICU at the end of the IMP-administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2012Feb 2016

First posted7 Mar 2012 (estimated)
Study startMar 2012
Primary completionFeb 2016
Study completionFeb 2016

Why it stopped: The Interim analysis (100 patients) revealed a possible harm to patients randomised to the fresh frozen plasma (FFP) treatment arm.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Major TraumaStudies of the same condition, open and under way.
More trials run by Medical University InnsbruckThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 100 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01545635
Sponsor's protocol ID: RETIC
Status last verified: Mar 2016
First submitted: 1 Mar 2012
Last updated: 23 Mar 2016
Results posted: No
Data monitoring committee: Yes

Publications

Innerhofer P, Fries D, Mittermayr M, Innerhofer N, von Langen D, Hell T, Gruber G, Schmid S, Friesenecker B, Lorenz IH, Strohle M, Rastner V, Trubsbach 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.
PubMed 28457980

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Major Trauma trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma
ClinicalTrials.gov ID: NCT01545635
Acronym / sponsor ID: RETIC
Conditions: Major Trauma
Keywords: Major trauma, Injury Severity Score, ISS > 15, clinical signs, risk of blood loss, coagulopathy, rotational thrombelastometry, ROTEM
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: The Interim analysis (100 patients) revealed a possible harm to patients randomised to the fresh frozen plasma (FFP) treatment arm.
Enrolment: 100 participants (actual)
Lead sponsor: Medical University InnsbruckUniversity, hospital or other
Study start: Mar 2012
Primary completion: Feb 2016 (actual)
Study completion: Feb 2016 (actual)
First posted: 7 Mar 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Besides coagulation management during ED treatment until 24h on ICU, patient's care is not influenced by the study and follows clinical routine.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Coagulation factor concentrates	Active comparator	Drug: Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrate
Fresh Frozen Plasma	Active comparator	Drug: Fresh Frozen Plasma blood type 0, A, B and AB

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Male and female subjects =/> 18 years and =/< 80 years
Major trauma (ISS > 15)
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
Presence of coagulopathy defined by ROTEM assays as follows,

Key exclusion criteria (15 listed)

Lethal injury
CPR on the scene,
Isolated brain injury, burn injury
Avalanche injury
Administration of FFP or coagulation factor concentrates before ED admission

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Fibrinogen concentrate, Prothrombin complex concentrate and FXIII concentrateFibrinogen 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	Coagulation factor concentrates
Fresh Frozen Plasma blood type 0, A, B and ABFresh 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	Drug	Fresh Frozen Plasma

Primary outcome

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.

Results and safety

The study was stopped early (reason given: The Interim analysis (100 patients) revealed a possible harm to patients randomised to the fresh frozen plasma (FFP) treatment arm.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2016.
Derived from this study: PubMed 28457980Innerhofer P, Fries D, Mittermayr M, Innerhofer N, von Langen D, Hell T, Gruber G, Schmid S, Friesenecker B, Lorenz IH, Strohle M, Rastner V, Trubsbach 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Multiple Organ Failure (MOF) (time frame: Variable until 24h on ICU at the end of the IMP-administration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01545635, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2016.