Universität zu Köln

Steiner, Thorsten ORCID: 0000-0002-5080-8222, Poli, Sven, Griebe, Martin, Huesing, Johannes, Hajda, Jacek, Freiberger, Anja, Bendszus, Martin, Boesel, Julian, Christensen, Hanne ORCID: 0000-0002-7472-3194, Dohmen, Christian, Hennerici, Michael, Kollmer, Jennifer, Stetefeld, Henning, Wartenberg, Katja E., Weimar, Christian, Hacke, Werner and Veltkamp, Roland (2016). Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurol., 15 (6). S. 566 - 574. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1474-4465

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Abstract

Background Haematoma expansion is a major cause of mortality in intracranial haemorrhage related to vitamin K antagonists (VKA-ICH). Normalisation of the international normalised ratio (INR) is recommended, but optimum haemostatic management is controversial. We assessed the safety and efficacy of fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC) in patients with VKA-ICH. Methods We did an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Patients aged at least 18 years with VKA-ICH who presented within 12 h after symptom onset with an INR of at least 2.0 were randomly assigned (1:1) by numbered sealed envelopes to 20 mL/kg of intravenous FFP or 30 IU/kg of intravenous four-factor PCC within 1 h after initial cerebral CT scan. The primary endpoint was the proportion of patients with INR 1.2 or lower within 3 h of treatment initiation. Masking of treatment was not possible, but the primary analysis was observer masked. Analyses were done using a treated-as-randomised approach. This trial is registered with EudraCT, number 2008-005653-37, and ClinicalTrials.gov, number NCT00928915. Findings Between Aug 7, 2009, and Jan 9, 2015, 54 patients were randomly assigned (26 to FFP and 28 to PCC) and 50 received study drug (23 FFP and 27 PCC). The trial was terminated on Feb 6, 2015, after inclusion of 50 patients after a safety analysis because of safety concerns. Two (9%) of 23 patients in the FFP group versus 18 (67%) of 27 in the PCC group reached the primary endpoint (adjusted odds ratio 30.6, 95% CI 4.7-197.9; p=0.0003). 13 patients died: eight (35%) of 23 in the FFP group (five from haematoma expansion, all occurring within 48 h after symptom onset) and five (19%) of 27 in the PCC group (none from haematoma expansion), the first of which occurred on day 5 after start of treatment. Three thromboembolic events occurred within 3 days (one in the FFP group and two in the PCC group), and six after day 12 (one and five). 43 serious adverse events (20 in the FFP group and 23 in the PCC group) occurred in 26 patients. Six serious adverse events were judged to be FFP related (four cases of haematoma expansion, one anaphylactic reaction, and one ischaemic stroke) and two PCC related (ischaemic stroke and pulmonary embolism). Interpretation In patients with VKA-related intracranial hemorrhage, four-factor PCC might be superior to FFP with respect to normalising the INR, and faster INR normalisation seemed to be associated with smaller haematoma expansion. Although an effect of PCC on clinical outcomes remains to be shown, our data favour the use of PCC over FFP in intracranial haemorrhage related to VKA.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Steiner, Thorsten UNSPECIFIED orcid.org/0000-0002-5080-8222 UNSPECIFIED Poli, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Griebe, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Huesing, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Hajda, Jacek UNSPECIFIED UNSPECIFIED UNSPECIFIED Freiberger, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Bendszus, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Boesel, Julian UNSPECIFIED UNSPECIFIED UNSPECIFIED Christensen, Hanne UNSPECIFIED orcid.org/0000-0002-7472-3194 UNSPECIFIED Dohmen, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hennerici, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Kollmer, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Stetefeld, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Wartenberg, Katja E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weimar, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hacke, Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Veltkamp, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-277971
DOI:	10.1016/S1474-4422(16)00110-1
Journal or Publication Title:	Lancet Neurol.
Volume:	15
Number:	6
Page Range:	S. 566 - 574
Date:	2016
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1474-4465
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACTIVATED FACTOR-VII; WARFARIN; REVERSAL; GUIDELINES; MANAGEMENT; EFFICACY; STROKE; SAFETY; PREVENTION; THERAPY Multiple languages Clinical Neurology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27797