Assessments and interventions
bleeding, tinnitus
BLEEDING, TINNITUS, HEARING IMPAIRMENT, BLOOD, COMPLICATIONS
Screening, enrollment, and randomization needed to be performed within a 36 h period. Audiometric tests at time of screening and after treatment (day 8) included pure tone and speech audiometry (specific national test per country to determine the dB hearing level (dB HL) value where 50% of single words will be understood; Germany: German language Freiburg Monosyllabic Test). Hearing impairment, and the occurrence and the degree of tinnitus was moreover assessed by means of a 11-item numeric rating scale (NRS) from 0 to 10. Laboratory tests before study drug administration included plasma fibrinogen concentration.Patients received the initial infusion of the IMP at day 1 (0.167 IU ancrod/kg bw/h or placebo). The dose was adjusted based on the screening fibrinogen concentration: 2 h infusion if screening fibrinogen concentration was ≥ 180 and ≤ 360 mg/dl, corresponding to a total dose of 0.33 IU/kg bw; 3 h infusion if screening fibrinogen concentration was > 360 mg/dl, corresponding to a total dose of 0.50 IU/kg bw. On day 2, again fibrinogen concentration was assessed to decide on proceeding with defibrinogenation treatment. If the fibrinogen concentration was < 50 mg/dl, the patient was taken off treatment. If it was ≥ 50 mg/dl, treatment proceeded with subcutaneous administration of either ancrod (1 IU/kg bw) or placebo on day 2, 4, and 6. This regimen was shown to be effective in defibrinogenation and was accompanied with the lowest incidence of bleeding complications [On day 8 the treatment effect was evaluated by above mentioned tests and during follow-up at day 30 and 90. Blood samples were taken for coagulation diagnostics, biomarkers, and neutralizing anti-ancrod antibodies at defined time points throughout the clinical trial.