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

NCT ID: NCT00928915

Last Updated: 2016-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2015-01-31

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?

Conditions

Intracranial Hemorrhages

Keywords

Intracranial Hemorrhages; Vitamin-K antagonist; Hemostatic treatment; Prothrombin complex; Fresh frozen plasma; Intracranial Hemorrhages related to vitamin-K antagonist

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prothrombin complex concentrate (PCC)

intravenously, 30 IU/kg

Group Type: EXPERIMENTAL

Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)

Intervention Type: DRUG

intravenous, repeated until INR ≤ 1.2

Fresh frozen plasma (FFP)

intravenously, 20ml/kg

Group Type: EXPERIMENTAL

Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)

Intervention Type: DRUG

intravenous, repeated until INR ≤ 1.2

Interventions

Prothrombin complex concentrate (PCC); fresh frozen plasma (FFP)

intravenous, repeated until INR ≤ 1.2

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

Thorsten Steiner

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thorsten Steiner, MR, PhD, MME

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Heidelberg University Hospital Germany

Locations

Heidelberg University Clinic

Heidelberg, , Germany

Countries

Germany

References

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 21557816 (View on PubMed)

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.

Reference Type: RESULT

PMID: 27302126 (View on PubMed)

Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD005951. doi: 10.1002/14651858.CD005951.pub5.

Reference Type: DERIVED

PMID: 37870112 (View on PubMed)

Other Identifiers

EUDRAT 2008-005653-37

Identifier Type: -

Identifier Source: secondary_id

AFmu-344/2008

Identifier Type: -

Identifier Source: org_study_id