PREVACT : Preventive REversal of Vitamine K Antagonist in Minor Craniocerebral Trauma (PREVACT)

Phase 3 Study Comparing Preventive Reversal of Vitamine K Antagonist Versus Reversion Only in Case of Intracranial Bleeding in Patients Receiving Vitamine K Antagonist Treatment

The occurence of a minor craniocerebral trauma in patients receiving vitamine K antagonist treatment leads to a high risk of bleeding.

Current guidelines recommend to perform a CT scan, and, in case of intracranial bleeding, to reverse anticoagulation with concomitant administration of prothrombin complex concentrates (PCCs) and vitamin K.

However, even if a reversion is performed, the prognostic of post-traumatic intracranial bleeding remain bad.

The investigators hypothesize that, for patients admitted in an emergency department after a minor head trauma and receiving anticoagulant treatment, a systematic preventive reversion with PCCs can lead to a significant reduction of intracranial haemorrhage and can also improve the neurological prognostic of patients versus the current strategy.

PREVACT will test this hypothesis, in an open label, randomized, multicentre, clinical trial involving 400 patients.

Study Overview

• Status: Terminated
• Conditions: Craniocerebral Trauma; Coagulation; Intravascular; Haemorrhage
• Intervention / Treatment: Drug: Reversion

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Agen, France
    • CH Agen
  • Angers, France, 49933
    • CHU Angers
  • Annecy, France
    • CH Annecy
  • Chateauroux, France
    • CHU Chateauroux
  • Clermont Ferrand, France
    • CHU Clermont Ferrand
  • Le Mans, France
    • CHG du Mans
  • Les Sables d'Olonne, France
    • CH Les Sables d'Olonne
  • Longjumeau, France
    • CH Longjumeau
  • Lyon, France
    • HCL Edouard Herriot
  • Metz, France
    • CHU Metz
  • Montauban, France
    • CHG Montauban
  • Nantes, France
    • CHU Nantes
  • Nice, France
    • CHU NICE
  • Paris, France
    • CHU Pitié Salpétrière
  • Paris, France
    • CHU Tenon
  • Poitiers, France
    • CHU Poitiers
  • Saint Brieuc, France
    • Chu Saint Brieuc
  • Saint Malo, France
    • CH Saint Malo
  • Toulouse, France
    • Chu Toulouse
  • Tours, France
    • CHU Tours
  • Versailles, France
    • CH Versailles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Admission in an emergency departement for a recent and isolated minor head trauma with at least one of the following characteristic : a period of alteration in the level of consciousness, a period of loss of consciousness (< 30 min), a posttraumatic amnesia, persistant posttraumatic headache, repeated vomitting (at least 2 episodes) or any other neurological sign such a convulsion or a localised neurological sign, wound of the scalp or the face testifying of the importance of the cranial trauma...
• Subject receiving anticoagulant treatment with anti-vitamin K for the treatment of atrial fibrillation (AF)
• Initial ED Glasgow Coma Scale (GCS) score of ≥13
• Achievable follow up
• Informed consent form signed by the patient or if he/she isn't able an emergency inclusion can be realised.

Exclusion Criteria:

• Delay between the minor head trauma and the possible preventive PCC's administration > 6h
• Subject receiving anticoagulant treatment other than anti vitamin K (heparin, fondaparinux, dabigatran, rivaroxaban, apixaban...)
• Subject receiving anticoagulant treatment for other reason than a AF
• Subject on antiplatelet treatment (except the use of low dose of aspirin (≤ 100 mg/day)
• Delocalised biology INR in capillary blood < 1.5 if it's available (only in departement where this analyse is a usual practice)
• Haemorrhage or suspected haemorrhage other than intracranial which could led to a reversion of the anticoagulation
• Head trauma associated with one or further potential haemorrhagic traumatic lesions
• Subject who reject the use of products derived from human blood
• Women who are pregnant
• Subject with any condition that, as judged by the investigator, would place the subject at increased risk of harm if he/she participated in the study
• Subject without social security registered

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Actual recommendations; Current guidelines recommend to perform a CT scan and realise the anticoagulation reversion only in case of intracranial bleeding diagnosed.	Drug: Reversion; Administration of prothrombin complex concentrates: KANOKAD before CT Scan; Other Names: KANOKAD
Experimental: Preventive reversion; Realise a preventive reversion before performing any CT scan.	Drug: Reversion; Administration of prothrombin complex concentrates: KANOKAD before CT Scan; Other Names: KANOKAD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of intracranial bleeding diagnosed in CT scan	This primary outcome measure will be analyse in a centralised place by two neuro-radiologist in blind of the randomised group.	24 hours +/- 4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volumetric measure of intracranial haemorrhage	This secondary outcome measure will be analyse in a centralised place by two neuro-radiologist in blind of the randomised group.	CT scan performed 24 hours +/-4 after inclusion
Percentage of patient having a decrease in their autonomy	A loss of at least one point in the Glasgow Outcome Score Extended	3 months
Percentage of patient having a systemic or neurologic ischemic attacks		1 month

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Investigators: Principal Investigator: ROY Pierre-Marie, Professor, UH Angers; Study Chair: TAZAROURTE Karim, Pr, UH Lyon

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): February 28, 2020
• Study Completion (Actual): September 3, 2020

Study Registration Dates

• First Submitted: October 9, 2013
• First Submitted That Met QC Criteria: October 10, 2013
• First Posted (Estimate): October 11, 2013

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Hemorrhage; Craniocerebral Trauma
• Other Study ID Numbers: PHRC 2012-02