International Normalized Ratio (INR) Normalization in Coumadin Associated Intracerebral Haemorrhage - Full Text View

Sponsor:	University of Heidelberg
Information provided by (Responsible Party):	Thorsten Steiner, University of Heidelberg
ClinicalTrials.gov Identifier:	NCT00928915

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 IV

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:

Genetics Home Reference related topics: COL4A1-related brain small-vessel disease

MedlinePlus related topics: Vitamin K

Drug Information available for: Vitamin K

U.S. FDA Resources

Further study details as provided by University of Heidelberg:

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

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

University of Heidelberg

Investigators

Principal Investigator:

Thorsten Steiner, MR, PhD, MME

Department of Neurology, Heidelberg University Hospital Germany

More Information

Publications:

Steiner T, Griebe M, Ivandic B, et al. Multicenter, prospective randomized trial on the use of prothrombin complex and fresh frozen plasma to normalize the INR in patients with coumadine related intracerebral hemorrhage related to vitamin K antagonists - The INCH-trial. Cerebovascular Disease 2009;27:185

Steiner T, Freiberger A, Griebe M, Hüsing J, Ivandic B, Kollmar R, Pfefferkorn T, Wartenberg KE, Weimar C, Hennerici M, Poli S. International normalised ratio normalisation in patients with coumarin-related intracranial haemorrhages--the INCH trial: a randomised controlled multicentre trial to compare safety and preliminary efficacy of fresh frozen plasma and prothrombin complex--study design and protocol. Int J Stroke. 2011 Jun;6(3):271-7. Epub 2011 Jan 10.

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 University of Heidelberg:

Intracranial Hemorrhages
Vitamin-K antagonist
Hemostatic treatment

Prothrombin complex
Fresh frozen plasma
Intracranial Hemorrhages related to vitamin-K antagonist

Additional relevant MeSH terms:

Hemorrhage
Intracranial Hemorrhages
Cerebral Hemorrhage
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Thrombin
Vitamin K

Vitamins
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012