E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Trauma patients with ongoing haemorrhage |
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E.1.1.1 | Medical condition in easily understood language |
Bleeding related to injuries sustained by trauma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10005103 |
E.1.2 | Term | Bleeding |
E.1.2 | System Organ Class | 100000004866 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10044461 |
E.1.2 | Term | Trauma |
E.1.2 | System Organ Class | 100000004863 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy and safety of an immediate pre-emptive first-line treatment with fibrinogen concentrate in patients with trauma haemorrhage in need of haemostatic resuscitation. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Trauma patient received directly from the scene of the accident AND • Age ≥ 18 years AND • Initiated order of transfusion of at least one blood component within the 1st hour of arrival AND • Predicted to need transfusion package therapy during the initial resuscitation (first 2 hours) AND • Consent obtainable from patient or scientific guardians (independent physicians and/or next of kin) |
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E.4 | Principal exclusion criteria |
• Duration of > 2 hours from arrival at trauma centre OR • Anticoagulant treatment (vitamin K antagonist, dabigatran, rivaroxiban, apixaban) OR • Severe isolated traumatic brain injury OR • Moribund patient with devastating injuries and expected to die within one hour of admission OR • Withdrawal from active therapy OR • Previously within 30 days included in a randomized trial, if known at the time of enrollment OR • Known body weight < 55 kg OR • Any blood product prior to inclusion |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Thrombelastograph (TEG®) Functional Fibrinogen (FF) maximum amplitude (MA) in mm |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• TEG® FF MA in mm at 2, 6 and 24 hours post intervention • TEG® MA in mm at 15 min, 2, 6 and 24 hours post intervention • Fibrinogen concentration (Clauss) at 15 min, 2, 6 and 24 hours post intervention • Transfusion requirements (RBC or FFP or PLT) at 6, 24 hours and total • Total use of haemostatic therapy • Time to intervention or placebo • Time to FFP and platelet transfusion • Percentage of patients receiving intervention or placebo < 1 hour of arrival • Time to anatomic haemostasis as noted by surgeon • Time to physiologic assessment of adequate resuscitation as noted by the surgeon and anaesthesiologist. Adequate resuscitation was based on qualitative improvement in blood pressure, urine output, and heart rate as well as decreased vasopressor requirements. No laboratory values or discrete measurements were required. • Time to both anatomic haemostasis and adequate resuscitation criteria were met, see two above • 24-hour and 30-day mortality • Severe adverse reactions |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
TEG parameters at 15 min, 2, 6 and 24 hours post intervention. Transfusion requirements at 6, 24 hours and total. Mortality at 24 hours and 30 days. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |