Table 2. Secondary efficacy and safety endpoints.
| Outcome | Timing of assessment |
| Efficacy parameters | |
| Global haemostatic response, based on requirement for additional haemostatic intervention (as per the primary endpoint) and haemoglobin level decrease | 60 min to 24 hours after initiation of the first IMP dose |
| Total amount of chest tube drainage | 12 and 24 hours after chest closure |
| Incidence of severe to massive bleeding, using a modification of the UDPB in cardiac surgery32 and its individual components | First 24 hours after surgery commencement, after the end of CPB and after IMP initiation |
| Mean number of total allogeneic blood products administered, including red cells, platelets and all (interventional and non-interventional) FP | First 24 hours after the end of CPB |
| Mean number of total non-interventional allogeneic blood products administered, including red cells, platelets and non-interventional FP | First 24 hours after the end of CPB |
| Mean number of total non-interventional allogeneic blood products administered, including red cells, platelets, cryoprecipitate and non-interventional FP | First 24 hours and 7 days after IMP initiation |
| Mean number and incidence of transfusion of individual allogeneic blood products (including red cells, platelets, cryoprecipitate and non-interventional FP), and incidence of administration of non-interventional coagulation factor products (including fibrinogen concentrate and rFVIIa) | First 24 hours and 7 days after surgery commencement, after the end of CPB and after IMP initiation |
| Incidences of ICH, GI haemorrhage and surgical re-exploration | First 24 hours after surgery commencement, after the end of CPB and after IMP initiation |
| Change in INR* | Within 30 min before to within 60 min after IMP initiation |
| Changes in coagulation parameters, including PT, aPTT, fibrinogen activity, ROTEM EXTEM CT and MCF, ROTEM FIBTEM MCF and platelets | Within 75 min before to within 75 min after IMP initiation |
| Time elapsed from initiation of first IMP dose to the patient’s arrival into the ICU | To be measured |
| Safety parameters | |
| Incidence of serious treatment-emergent adverse events, individually and as a composite where appropriate (eg, TEEs, MACE) | All from the beginning of surgery up to postoperative day 30 |
| Duration of mechanical ventilation, ICU stay and hospitalisation | |
| Incidence of death | |
| Number of days alive and out of hospital | |
*
INR reduction will be considered successful if the magnitude of the reduction is >1.0 or the post-treatment level falls to below 1.5.
aPTT, activated partial thromboplastin time; CPB, cardiopulmonary bypass; CT, clotting time; GI, gastrointestinal; ICH, intracerebral haemorrhage; ICU, intensive care unit; IMP, investigational medicinal product; INR, international normalised ratio; MACE, major adverse cardiac events; MCF, maximum clot firmness; PT, prothrombin time; rFVIIa, activated recombinant factor VII; ROTEM, rotational thromboelastometry; TEEs, thromboembolic events; UDPB, universal definition of perioperative bleeding