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

NCT00928915 | Completed Phase 4 DMC

• 2 other identifiers: AFmu-344/2008EUDRAT 2008-005653-37
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• INR ≤ 1.2 within 3 hours after start of drug infusion

  3 hours

Secondary Outcomes (3)

• Safety: Number of thromboembolic events

  90 days

• Efficacy: Percentage of volume increase

  24 hours

• Clinical outcome

  day 90

Study Arms (2)

Prothrombin complex concentrate (PCC)

EXPERIMENTAL

intravenously, 30 IU/kg

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

Fresh frozen plasma (FFP)

EXPERIMENTAL

intravenously, 20ml/kg

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

Interventions

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

intravenous, repeated until INR ≤ 1.2

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Heidelberg University: lead

Study Sites (1)

Heidelberg University Clinic

Heidelberg, 69120, Germany

Location

Related Publications (4)

• 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

  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.

  PMID: 21557816 BACKGROUND

• 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.

  PMID: 27302126 RESULT

• 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.

  PMID: 37870112 DERIVED

MeSH Terms

Conditions

Intracranial Hemorrhages

Interventions

Factor IX

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Officials

• Thorsten Steiner, MR, PhD, MME

  Department of Neurology, Heidelberg University Hospital Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: June 25, 2009
• First Posted: June 26, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: October 26, 2016

Record last verified: 2016-10

Locations

DE (1)