- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00928915
International Normalized Ratio (INR) Normalization in Coumadin Associated Intracerebral Haemorrhage (INCH)
Multicenter, Prospective Randomized Trial on the Use of Prothrombin Complex and Fresh Frozen Plasma in Patients With Intracerebral Hemorrhage Related to Vitamin K Antagonists
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?
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Heidelberg, Germany, 69120
- Heidelberg University Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Prothrombin complex concentrate (PCC)
intravenously, 30 IU/kg
|
intravenous, repeated until INR ≤ 1.2
|
Experimental: Fresh frozen plasma (FFP)
intravenously, 20ml/kg
|
intravenous, repeated until INR ≤ 1.2
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
INR ≤ 1.2 within 3 hours after start of drug infusion
Time Frame: 3 hours
|
3 hours
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety: Number of thromboembolic events
Time Frame: 90 days
|
90 days
|
Efficacy: Percentage of volume increase
Time Frame: 24 hours
|
24 hours
|
Clinical outcome
Time Frame: day 90
|
day 90
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Thorsten Steiner, MR, PhD, MME, Department of Neurology, Heidelberg University Hospital Germany
Publications and helpful links
General 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, Husing 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. doi: 10.1111/j.1747-4949.2010.00560.x. Epub 2011 Jan 10.
- Steiner T, Poli S, Griebe M, Husing J, Hajda J, Freiberger A, Bendszus M, Bosel J, Christensen H, Dohmen C, Hennerici M, Kollmer J, Stetefeld H, Wartenberg KE, Weimar C, Hacke W, Veltkamp R. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurol. 2016 May;15(6):566-73. doi: 10.1016/S1474-4422(16)00110-1. Epub 2016 Apr 11.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AFmu-344/2008
- EUDRAT 2008-005653-37
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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