Clinical Trial Results:
A multicenter double-blind, placebo controlled, randomized, pilot trial to assess the efficacy of pre-hospital administration of Fibrinogen Concentrate (FGTW) in trauma patients, presumed to bleed (FI in TIC)
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Summary
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EudraCT number |
2010-022923-31 |
Trial protocol |
AT DE CZ |
Global end of trial date |
18 Nov 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Sep 2021
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First version publication date |
10 Sep 2021
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Other versions |
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Summary report(s) |
FINTIC Publication in EJA 2021 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
FIinTIC
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01475344 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Medical Universität of Innsbruck
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Sponsor organisation address |
Anichstrasse 35, Insnbruck, Austria,
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Public contact |
Clinical Trial Office Dr. Fries, Medical University of Innsbruck, 0043 0512504 80451, mirjam.bachler@i-med.ac.at
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Scientific contact |
Clinical Trial Office Dr. Fries, Medical University of Innsbruck, 0043 0512504 80451, mirjam.bachler@i-med.ac.at
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Jan 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Nov 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Nov 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To asses whether the ultra-early pro-coagulatory treatment with fibrinogen concentrate on the scene would improve plasmatic coagulation capacity in multiple trauma patients with bleeding and/or major blood loss.
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Protection of trial subjects |
To protect the trial subjects the study was conducted in compliance with Good Clinical Practices, the Declaration of Helsinki in its latest version, the local laws and regulations and the applicable regulatory requirements. An on-site monitoring was set up to check the safety of patients.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Aug 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 61
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Country: Number of subjects enrolled |
Czechia: 2
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Country: Number of subjects enrolled |
Germany: 4
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Worldwide total number of subjects |
67
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EEA total number of subjects |
67
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
56
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
The recruitment was planned to last until 60 (2x30) evaluable patients will be included. The global recruitment process started in August 2011 in Tyrol, Austria with the Center Christophorus 1 and Medical University of Innsbruck. In August 2013 the centers in Germany and in June 2015 the centers in the Czech Republic were initiated. | |||||||||
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Pre-assignment
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Screening details |
Severely injured patients aged at least 18 years with major bleeding and need for volume replacement therapy were screened and enrolled by experienced emergency physicians at the scene of trauma. Admission to one of the study trauma centres was required to ensure adhere to the study protocol. | |||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||
Blinding implementation details |
The placebo was also designed to have the same physical form (powder) as fibrinogen concentrate. FGTW and placebo were packaged in the same type of vials and boxes to preserve the double-blinding. The packaging for one patient is calculated for a maximum weight of 120 kg.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Fibrinogen concentrate | |||||||||
Arm description |
Patients allocated to the fibrinogen group received 50 mg/kg Body Weight fibrinogen concentrate (one 100 ml vial of 1.5 g of fibrinogen for each 30 kg body weight, estimated by the emergency physician). | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Fibrinogen concentrate
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Investigational medicinal product code |
FGTW
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Other name |
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Pharmaceutical forms |
Powder and solvent for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The study drug dose was 1.5 g per 30 kg of estimated body weight to achieve the recommended dosage of 50 mg/kg. To enable the administration of the recommended dosage, the patients were stratified by the emergency physician into different body weight groups (30-kg steps). A dose of 3 g of the study drug was given in patients with bodyweight 30 to 60 kg, 4.5 g in patients with bodyweight 60 to 90 kg and 6 g in patients with bodyweight 90 to 120 kg. For all patients weighing 120 kg or more, the dose was still 6 g because blood volume increases only slightly with increasing obesity. Each 1.5 g of powder was reconstituted in 100 ml of solvent. The study drug was administered via an intravenous infusion at a rate of 20 ml/min, either at the scene of trauma or during transportation to the participating hospital.
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Arm title
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Placebo | |||||||||
Arm description |
Patients allocated to the placebo group received 50 mg/kg Body Weight placebo powder (one 100 ml vial of 1.5 g of fibrinogen for each 30 kg body weight, estimated by the emergency physician). | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The placebo dose was 1.5 g per 30 kg of estimated body weight to achieve the recommended dosage of 50 mg/kg. To enable the administration of the recommended dosage, the patients were stratified by the emergency physician into different body weight groups (30-kg steps). A dose of 3 g of the placebo was given in patients with bodyweight 30 to 60 kg, 4.5 g in patients with bodyweight 60 to 90 kg and 6 g in patients with bodyweight 90 to 120 kg. For all patients weighing 120 kg or more, the dose was still 6 g because blood volume increases only slightly with increasing obesity. Each 1.5 g of powder was reconstituted in 100 ml of solvent. The placebo was administered via an intravenous infusion at a rate of 20 ml/min, either at the scene of trauma or during transportation to the participating hospital.
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Baseline characteristics reporting groups
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Reporting group title |
Fibrinogen concentrate
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Reporting group description |
Patients allocated to the fibrinogen group received 50 mg/kg Body Weight fibrinogen concentrate (one 100 ml vial of 1.5 g of fibrinogen for each 30 kg body weight, estimated by the emergency physician). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Patients allocated to the placebo group received 50 mg/kg Body Weight placebo powder (one 100 ml vial of 1.5 g of fibrinogen for each 30 kg body weight, estimated by the emergency physician). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full analysis
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All analyses were conducted in the modified intention-to-treat (ITT) population, that is all patients receiving fibrinogen concentrate or placebo in whom posttreatment assessment of FIBTEM MCF was available and all inclusion/exclusion criteria were fullfilled at re-check of the criteria in the hospital.
After randomisation, four patients in the fibrinogen concentrate group and three patients in the placebo group were withdrawn from the study due to previously undetected fulfilment of exclusion criteria. A further seven patients (five from the fibrinogen concentrate arm and two from the placebo arm) were excluded due to missing data for the primary endpoint. Thus, the modified ITT population comprised 28 patients in the fibrinogen concentrate arm and 25 patients in the placebo arm.
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End points reporting groups
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Reporting group title |
Fibrinogen concentrate
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Reporting group description |
Patients allocated to the fibrinogen group received 50 mg/kg Body Weight fibrinogen concentrate (one 100 ml vial of 1.5 g of fibrinogen for each 30 kg body weight, estimated by the emergency physician). | ||
Reporting group title |
Placebo
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Reporting group description |
Patients allocated to the placebo group received 50 mg/kg Body Weight placebo powder (one 100 ml vial of 1.5 g of fibrinogen for each 30 kg body weight, estimated by the emergency physician). | ||
Subject analysis set title |
Full analysis
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All analyses were conducted in the modified intention-to-treat (ITT) population, that is all patients receiving fibrinogen concentrate or placebo in whom posttreatment assessment of FIBTEM MCF was available and all inclusion/exclusion criteria were fullfilled at re-check of the criteria in the hospital.
After randomisation, four patients in the fibrinogen concentrate group and three patients in the placebo group were withdrawn from the study due to previously undetected fulfilment of exclusion criteria. A further seven patients (five from the fibrinogen concentrate arm and two from the placebo arm) were excluded due to missing data for the primary endpoint. Thus, the modified ITT population comprised 28 patients in the fibrinogen concentrate arm and 25 patients in the placebo arm.
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End point title |
Fibrinogen polymerisation measure with the FIBTEM MCF at V2 | ||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
ROTEM FIBTEM MCF measurements at visit 2 (emergency department after termination of the IMP administration).
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| Notes [1] - Modified ITT population is used [2] - Modified ITT population is used |
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Statistical analysis title |
Statistical assessment of primary endpoint | ||||||||||||||||
Statistical analysis description |
Initial analysis of the FIBTEM MCF results (Shapiro--Wilk normality test) showed that the data were not normally distributed. A revised sample size calculation, based on the observed changes in FIBTEM MCF, implied that 20 patients per group would be sufficient to detect a 1 mm difference in FIBTEM MCF change with a power of 80%. The Wilcoxon rank sum test was used to assess between-group and within-group differences in FIBTEM MCF.
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Comparison groups |
Fibrinogen concentrate v Placebo
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Number of subjects included in analysis |
53
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||
Confidence interval |
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End point title |
Fibrinogen levels (Clauss) at V2 | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Fibrinogen levels (mg/dl) at visit 2 (emergency department after termination of the IMP administration).
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
All adverse events, regardless of relationship or seriousness were recorded from IMP administration until the visit T7 at day 7 (half-life of FGTW is 3.5 days).
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
15
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| Frequency threshold for reporting non-serious adverse events: 5% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Since these were critically ill patients, the reported non-serious adverse events were too numerous to list them in the full data set. Three (5.7%) thromboembolic complications occurred within 7 days after the administration of the study drug. Two thromboembolic events were detected in patients who had received fibrinogen concentrate and one event in patients who received placebo. The difference was not significant. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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20 Dec 2013 |
- Inclusion criterion I.3.: Removal of “with parameters of shock” since many patients don´t show parameters of shock when the emergency physician arrives at the scene of accident
- Exclusion criterion E.1: Change from “Penetrating trauma” to “Solely penetrating trauma” to clarify that polytrauma patients with also a penetrating trauma can be included.
- Exclusion criterion E.3: Ongoing hemodynamic instability was simpler defined.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
