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

Intracranial Hemorrhages Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00928915
• Other study ID #: AFmu-344/2008
• Secondary ID: EUDRAT 2008-0056
• Status: Completed
• Phase: Phase 4
• First received: June 25, 2009
• Last updated: October 24, 2016
• Start date: July 2009
• Est. completion date: January 2015

Study information

• Verified date: October 2016
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesGermany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracranial Hemorrhages

Intervention

Drug:
• Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)
intravenous, repeated until INR = 1.2

Locations

Country	Name	City	State
Germany	Heidelberg University Clinic	Heidelberg

Sponsors (1)

Lead Sponsor	Collaborator
Heidelberg University

Country where clinical trial is conducted

Germany, 

References & Publications (3)

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. doi: 10.1111/j.1747-4949.2010.00560.x. Epub 2011 Jan 10. — View 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

Steiner T, Poli S, Griebe M, Hüsing J, Hajda J, Freiberger A, Bendszus M, Bösel 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 pa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	INR = 1.2 within 3 hours after start of drug infusion		3 hours	Yes
Secondary	Safety: Number of thromboembolic events		90 days	Yes
Secondary	Efficacy: Percentage of volume increase		24 hours	Yes
Secondary	Clinical outcome		day 90	No