FFP versus PCC in patients with ICH related to vitamin K antagonists

INCH was an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial, assessing the safety and efficacy of fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC, octaplex^®) in patients with intracranial haemorrhage related to vitamin K antagonists (VKA-ICH).

Patients

50 patients ≥18 years, with VKA-ICH who presented within 12 h after symptom onset with an INR of at least 2·0.

Intervention

Patients were randomly assigned (1:1) to 20 mL/kg of intravenous FFP (N=23) or 30 IU/kg of intravenous four-factor PCC (N=27) within 1 h after initial cerebral CT scan.

Primary objective

The proportion of patients with INR 1·2 or lower within 3 h of treatment initiation.

Efficacy

A significantly higher number of patients achieving an INR ≤1.2 in the octaplex^® group compared to those treated with FFP (adjusted odds ratio 30·6, 95% CI 4·7–197·9; p=0·0003).

Figure 1: Patients achieving INR≤1.2 with octaplex^® versus FFP

Figure 2: octaplex^® versus FFP on haematoma expansion

Safety

There were fewer deaths (classified as a clinical outcome) at day 90 with octaplex^® than FFP (5 vs 8; p=0.14). Five of these deaths in the FFP group occurred within 48 hours and were due to haematoma expansion. No deaths in the octaplex^® groups were due to haematoma expansion as a clinical outcome, and there were no deaths within the first 5 days 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).

The trial was terminated on Feb 6, 2015, after the inclusion of 50 patients after a safety analysis because of safety concerns with the use of FFP.

Reference:

Steiner T, Poli S, Griebe M, Hüsing J, Hajda J, Freiberger A, Bendszus M, Bösel 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. [PubMed]