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

October 24, 2016 updated by: Thorsten Steiner, Heidelberg University

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

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Heidelberg, Germany, 69120
        • Heidelberg University Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Thorsten Steiner, MR, PhD, MME, Department of Neurology, Heidelberg University Hospital Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

June 25, 2009

First Submitted That Met QC Criteria

June 25, 2009

First Posted (Estimate)

June 26, 2009

Study Record Updates

Last Update Posted (Estimate)

October 26, 2016

Last Update Submitted That Met QC Criteria

October 24, 2016

Last Verified

October 1, 2016

More Information

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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