Stroke

INCH trial

The International normalized ratio (INR) normalization in Coumadin-induced intracerebral haemorrhage (INCH) trial compared the effect of intravenous 4 factor-prothrombin complex concentrate (PCC, 30 U/kg) and fresh frozen plasma (FFP, 20 ml/kg) on INR applied within 12 hours of symptom onset of intracerebral haemorrhage (ICH) occurrence related to vitamin-K-anatagonists (VKA).

Authors (alphabetically): Milija Mijajlovic, Simona Sacco, Thorsten Steiner

Reviewer’s/Authors’ affiliation
Neurology Clinic, Clinical Center of Serbia and School of Medicine University of Belgrade, Serbia (MM)
Institute of Neurology, Department of Applied Clinical Sciences and Biotechnology, University of L’Aquila, L’Aquila, Italy (SS)
Department of Neurology, Klinikum Frankfurt Höchst, and Heidelberg University Hospital, Germany (TS)

Pubmed / web link(s) to the work reviewed/cited.
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;15:566–573; DOI 10.1016/S1474-4422(16)00110-1
ClinicalTrials.gov, number NCT00928915

Comment: 150-250 words.
The International normalized ratio (INR) normalization in Coumadin-induced intracerebral haemorrhage (INCH) trial compared the effect of intravenous 4 factor-prothrombin complex concentrate (PCC, 30 U/kg) and fresh frozen plasma (FFP, 20 ml/kg) on INR applied within 12 hours of symptom onset of intracerebral haemorrhage (ICH) occurrence related to vitamin-K-anatagonists (VKA).
Fifty of 54 randomized patients had received study drug, when the trial was prematurely terminated because of safety concerns. The primary endpoint - the normalization of INR within 3 hours after start of infusion – occurred in 2 of 23 (9%) patients in the FFP-group and in 18 of 27 (67%) patients in the PCC-group (adjusted odds ratio 30.6, 95% CI 4.7–197.9; p=0.0003). Haematoma expansion at 3 hours and 24 hours was significantly higher in the FFP than in the PCC group. Mortality rate was 35% (8/23) and 19% (5/27) in the FFP- and PCC-Group respectively. Five of the 8 patients in the FFP-group died within the first 48 hours all by hematoma expansion. Post-hoc analysis did not demonstrate an association between hematoma expansion, and elevated blood pressure due to volume overload in the FFP-group.

Reference:
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;15:566–573

Key points:
1.    The significantly faster effect of 4-factor PCC on anticoagulation reversal compared to FFP corresponded to decreased early cerebral hematoma expansion at 3 and 24 hours.
2.    INCH lends biological plausibility to the concept that rapid and effective anticoagulation reversal reduces intracerebral hematoma expansion in vitamin-K-antagonists related ICH, and
3.    potentially also for ICH related to non-vitamin-K oral anticoagulants