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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by Heidelberg University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Thorsten Steiner, University of Heidelberg
ClinicalTrials.gov Identifier:
NCT00928915
First received: June 25, 2009
Last updated: November 3, 2011
Last verified: November 2011
  Purpose

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 ]

Estimated Enrollment: 74
Study Start Date: July 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: December 2012 (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

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00928915

Contacts
Contact: Thorsten Steiner, Prof. Dr. +49 69 3106 2932 thorsten_steiner@med.uni-heidelberg.de

Locations
Germany
Heidelberg University Clinic Recruiting
Heidelberg, Germany, 69120
Contact: Sven Poli, Dr.    +49 6221 56 38746    sven_poli@med.uni-heidelberg.de   
Principal Investigator: Thorsten Steiner, Prof. Dr.         
Sponsors and Collaborators
Heidelberg University
Investigators
Principal Investigator: Thorsten Steiner, MR, PhD, MME Department of Neurology, Heidelberg University Hospital Germany
  More Information

Publications:
Responsible Party: Thorsten Steiner, Prof. Dr., University of Heidelberg
ClinicalTrials.gov Identifier: NCT00928915     History of Changes
Other Study ID Numbers: AFmu-344/2008, EUDRAT 2008-005653-37
Study First Received: June 25, 2009
Last Updated: November 3, 2011
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:
Hemorrhage
Cerebral Hemorrhage
Intracranial Hemorrhages
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Vitamins
Vitamin K
Thrombin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014