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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00928915
Recruitment Status : Completed
First Posted : June 26, 2009
Last Update Posted : October 26, 2016
Information provided by (Responsible Party):
Thorsten Steiner, Heidelberg University

Brief Summary:

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 or disease Intervention/treatment Phase
Intracranial Hemorrhages Drug: Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP) Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : July 2009
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. INR ≤ 1.2 within 3 hours after start of drug infusion [ Time Frame: 3 hours ]

Secondary Outcome Measures :
  1. Safety: Number of thromboembolic events [ Time Frame: 90 days ]
  2. Efficacy: Percentage of volume increase [ Time Frame: 24 hours ]
  3. Clinical outcome [ Time Frame: day 90 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00928915

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

Publications of Results:
Other Publications:
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Responsible Party: Thorsten Steiner, Prof. Dr., Heidelberg University Identifier: NCT00928915     History of Changes
Other Study ID Numbers: AFmu-344/2008
EUDRAT 2008-005653-37
First Posted: June 26, 2009    Key Record Dates
Last Update Posted: October 26, 2016
Last Verified: October 2016
Keywords provided by Thorsten Steiner, 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:
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Vitamin K
Cerebral Hemorrhage
Intracranial Hemorrhages
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action