International Normalized Ratio (INR) Normalization in Coumadin Associated Intracerebral Haemorrhage "INCH"

Terminated

Phase 4 Results N/A

Trial Description

Intracerebral haemorrhage (ICH) is the most feared complication in patients on vitamin K antagonists (VKA). VKA related ICH occurs 8-10 times more frequently and the mortality is 2 times higher than in non-anticoagulated patients. Mortality may rise up to 67%. The higher mortality rate may in part be due to the higher rate of haematoma expansion (HE) over a longer period after symptom onset. International guidelines recommend treatment of VKA-ICH with prothrombin complex (PCC) or fresh-frozen plasma (FFP) both in combination with Vitamin-K. But these recommendations are not based on randomized controlled trials. It is known that these drugs lower the INR, and thus it is assumed that normalization of coagulopathy may lead to haemostasis and reduction of HE. Safety and efficacy of these treatments have never been studied in a prospective controlled trial.
The investigators' questions are: How potent are PCC and FFP in normalization of the INR? What is the safety profile of each of these drugs?

Trial Stopped: Review by official authorities

Conditions

Interventions

  • Fresh Frozen Plasma Biological
    Other Names: FFP
    Intervention Desc: Fresh Frozen Plasma (FFP) is defined as the fluid portion of one unit of human blood that has been centrifuged, separated, and frozen solid at -18°C (or colder) within 6 hours of collection.
  • Prothrombin Complex Concentrate (PCC) (Octaplex)Drug
    Intervention Desc: PCC is a combination of blood clotting factors II, VII, IX and X. It reverses the effect of warfarin (a coumarin anti-coagulant) and is used in cases of significant bleeding in patients with a coagulopathy (INR > 8.0, prolonged prothrombin time, raised d-dimer).
  • Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP) Drug
    Intervention Desc: intravenous, repeated until INR ≤ 1.2
    ARM 1: Kind: Experimental
    Label: Prothrombin complex concentrate (PCC)
    Description: intravenously, 30 IU/kg
    ARM 2: Kind: Experimental
    Label: Fresh frozen plasma (FFP)
    Description: intravenously, 20ml/kg

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Pharmacokinetics/Dynamics Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients will be randomized to one of two arms: 1) Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP) IV, repeated until INR ? 1.2 or 2) Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP) IV, repeated until INR ? 1.2.

Outcomes

Type Measure Time Frame Safety Issue
Primary INR ? 1.2 within 3 hours after start of drug infusion
Secondary Safety: Number of thromboembolic events; Efficacy: Percentage of volume increase; Clinical outcome.
Primary INR ≤ 1.2 within 3 hours after start of drug infusion 3 hours Yes
Secondary Safety: Number of thromboembolic events 90 days Yes
Secondary Efficacy: Percentage of volume increase 24 hours Yes
Secondary Clinical outcome day 90 No

Sponsors