International Normalized Ratio (INR) Normalization in Coumadin Associated Intracerebral Haemorrhage (INCH)
Primary Purpose
Intracranial Hemorrhages
Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)
Sponsored by
About this trial
This is an interventional treatment trial for Intracranial Hemorrhages focused on measuring Intracranial Hemorrhages, Vitamin-K antagonist, Hemostatic treatment, Prothrombin complex, Fresh frozen plasma, Intracranial Hemorrhages related to vitamin-K antagonist
Eligibility 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
Sites / Locations
- Heidelberg University Clinic
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Prothrombin complex concentrate (PCC)
Fresh frozen plasma (FFP)
Arm Description
intravenously, 30 IU/kg
intravenously, 20ml/kg
Outcomes
Primary Outcome Measures
INR ≤ 1.2 within 3 hours after start of drug infusion
Secondary Outcome Measures
Safety: Number of thromboembolic events
Efficacy: Percentage of volume increase
Clinical outcome
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00928915
Brief Title
International Normalized Ratio (INR) Normalization in Coumadin Associated Intracerebral Haemorrhage
Acronym
INCH
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 Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Heidelberg University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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?
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intracranial Hemorrhages
Keywords
Intracranial Hemorrhages, Vitamin-K antagonist, Hemostatic treatment, Prothrombin complex, Fresh frozen plasma, Intracranial Hemorrhages related to vitamin-K antagonist
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prothrombin complex concentrate (PCC)
Arm Type
Experimental
Arm Description
intravenously, 30 IU/kg
Arm Title
Fresh frozen plasma (FFP)
Arm Type
Experimental
Arm Description
intravenously, 20ml/kg
Intervention Type
Drug
Intervention Name(s)
Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)
Intervention Description
intravenous, repeated until INR ≤ 1.2
Primary Outcome Measure Information:
Title
INR ≤ 1.2 within 3 hours after start of drug infusion
Time Frame
3 hours
Secondary Outcome Measure Information:
Title
Safety: Number of thromboembolic events
Time Frame
90 days
Title
Efficacy: Percentage of volume increase
Time Frame
24 hours
Title
Clinical outcome
Time Frame
day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thorsten Steiner, MR, PhD, MME
Organizational Affiliation
Department of Neurology, Heidelberg University Hospital Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Heidelberg University Clinic
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
12. IPD Sharing Statement
Citations:
Citation
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
Results Reference
background
PubMed Identifier
21557816
Citation
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.
Results Reference
background
PubMed Identifier
27302126
Citation
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.
Results Reference
result
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International Normalized Ratio (INR) Normalization in Coumadin Associated Intracerebral Haemorrhage
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