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

This study has been terminated.
(Review by official authorities)
Information provided by (Responsible Party):
Thorsten Steiner, Heidelberg University Identifier:
First received: June 25, 2009
Last updated: May 26, 2015
Last verified: May 2015

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?

Condition Intervention Phase
Intracranial Hemorrhages
Drug: Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter, Prospective Randomized Trial on the Use of Prothrombin Complex and Fresh Frozen Plasma in Patients With Intracerebral Hemorrhage Related to Vitamin K Antagonists

Resource links provided by NLM:

Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • INR ≤ 1.2 within 3 hours after start of drug infusion [ Time Frame: 3 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety: Number of thromboembolic events [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
  • Efficacy: Percentage of volume increase [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  • Clinical outcome [ Time Frame: day 90 ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: July 2009
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prothrombin complex concentrate (PCC)
intravenously, 30 IU/kg
Drug: Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)
intravenous, repeated until INR ≤ 1.2
Experimental: Fresh frozen plasma (FFP)
intravenously, 20ml/kg
Drug: Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)
intravenous, repeated until INR ≤ 1.2


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Spontaneous ICH (intraparenchymal), subdural hematoma (SDH) diagnosed by CT scanning ≤ 12 hours after onset of symptoms. In case of unknown time of symptom onset: time between last seen in healthy condition and first CCT ≤ 12 hours.
  • Therapy receiving vitamin K antagonists (VKA)
  • International Normalized Ratio (INR) ≥ 2
  • Signed informed consent form, or signed informed consent by a legal representative, judicial consent in cases where no legal representative is available in time, or consent of an independent physician familiar with the indication in cases where the first three possibilities can not be realized.

Exclusion Criteria:

  • Patients with ICH not related to vitamin-K antagonist therapy or
  • Patients with secondary ICH related to infarction, hemophilia or other coagulopathy, tumor, hemorrhagic infarction, cerebrovenous thrombosis, aneurysm, arteriovenous malformations (AVM) or severe trauma
  • Deep Coma (GCS ≤ 5) at the time of admission or before intubation if intubated outside the hospital
  • Known previous disability (mRS > 2 before stroke occurred)
  • Acute myocardial ischemia, acute septicemia, acute crush injury, any history of acute hemorrhagic disseminated intravascular coagulation, acute thrombotic stroke
  • Known history of intermittent claudication
  • Known recent thrombotic event < 30 days
  • Acute or known congestive heart failure (NYHA III, IV)
  • Pulmonary edema
  • Known liver failure (child-pugh-score C)
  • Known alcohol or other drug abuse
  • Known active malignant disease
  • Known thrombocytopenia (platelets <50,000/µL), hemorrhagic diathesis (primary defects of coagulation, fibrinolysis, platelets)
  • History of hypersensitivity to the investigational products or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational product
  • Known allergy to heparin or history of heparin induced thrombocytopenia.
  • Pregnancy and lactation
  • Concomitant use of antithrombotic (with PTT > 1.5 of normal PTT), thrombolytic treatment.
  • Use of aspirin, clopidogrel or dipyridamole or combinations thereof (e.g. Aggrenox®) is not an exclusion criterion. These drugs should be discontinued and not restarted earlier than 24 hours after normalization of INR if indicated.
  • Previous participation in this trial
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Please refer to this study by its identifier: NCT00928915

Heidelberg University Clinic
Heidelberg, Germany, 69120
Sponsors and Collaborators
Heidelberg University
Principal Investigator: Thorsten Steiner, MR, PhD, MME Department of Neurology, Heidelberg University Hospital Germany
  More Information

Responsible Party: Thorsten Steiner, Prof. Dr., Heidelberg University Identifier: NCT00928915     History of Changes
Other Study ID Numbers: AFmu-344/2008  EUDRAT 2008-005653-37 
Study First Received: June 25, 2009
Last Updated: May 26, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Germany: Paul-Ehrlich-Institut

Keywords provided by Heidelberg University:
Intracranial Hemorrhages
Vitamin-K antagonist
Hemostatic treatment
Prothrombin complex
Fresh frozen plasma
Intracranial Hemorrhages related to vitamin-K antagonist

Additional relevant MeSH terms:
Cerebral Hemorrhage
Intracranial Hemorrhages
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Pathologic Processes
Vascular Diseases
Vitamin K
Antifibrinolytic Agents
Fibrin Modulating Agents
Growth Substances
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Vitamins processed this record on May 23, 2016