Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as AngioMAX, Angiox, Angiomax (bivalirudin) anticoagulant
bivalirudin · 8 trials · 10 indications
Major bleeding (Bleeding Academic Research Consortium \[BARC\] type ≥3b) was defined as follows: * Bleeds that were evident clinically, or by laboratory or imaging results, which resulted in surgical intervention or administration of IV vasoactive drugs; overt bleeds with a hemoglobin drop of at least 5 grams per deciliter (g/dL); and bleeding that caused cardiac tamponade. * BARC 3c includes intracranial or intraocular bleeds that compromised vision. * BARC type 4 (Coronary Artery Bypass Grafting \[CABG\]-related bleeding) includes perioperative intracranial bleeding within 48 hours, bleeds that result in reoperation following closure of sternotomy for the purpose of controlling bleeding, bleeds that result in treatment with transfusion of ≥5 units of whole blood or packed red blood cells within a 48 hour period; and chest tube output ≥2 liters (L) within a 24-hour period. * BARC type 5, fatal bleeding, describes bleeds that directly result in death with no other cause.
The net adverse cardiac events (NACE) at 30 days is the composite of major adverse cardiovascular events (MACE) + major bleeding (BARC type ≥3b). The composite of MACE is defined as all-cause mortality, myocardial infarction (MI), and stroke. A participant was defined to have a composite event if the participant experienced at least 1 of the components. If the participant did not have any of the components, then he or she did not have the composite endpoint. If a participant had more than 1 of the components, he or she was only counted once in the determination of the total number of participants experiencing the composite endpoint.
A participant was defined to have had a composite event if the participant experienced at least 1 of the 2 components (death or non-CABG major bleeding) of the composite. Incidence=the number of participants to experience the event/total number of at risk participants x 100. Death was defined as death from any cause at any time. Non-CABG major bleeding was defined as any 1 of the following: intra-cranial, retroperitoneal, intraocular, access site hemorrhage requiring radiological or surgical intervention, reduction in hemoglobin (Hb) concentration of \>4 grams/deciliter (g/dL) without an overt source of bleeding, reduction in hemoglobin concentration of \>3 g/dL with an overt source of bleeding; re-intervention for bleeding, or use of any blood product transfusion.
In-hospital acute procedural success, defined as the absence of death, Q wave MI, repeat coronary revascularization, and stroke (hemorrhagic or ischemic) at hospital discharge or Day 7 after surgery ('Day 7/discharge'), whichever occurs first.
composite incidence of major bleeding events during administration or within 48 hours after stopping bivalirudin
| Arm | Type | Description |
|---|---|---|
| Bivalirudin | EXPERIMENTAL | Bivalirudin administered as a bolus and intravenous (IV) infusion during TAVR. It was recommended that the bolus (0.75 milligrams per kilogram \[mg/kg\]) be directly administered through the valve delivery sheath immediately following its successful delivery via percutaneous femoral access. Systemic IV administration of the bolus dose was also acceptable. The bivalirudin IV infusion was initiated immediately after the bolus administration. All wires, catheters, and sheaths were to be flushed with heparinized saline. |
| Unfractionated heparin (UFH) | ACTIVE_COMPARATOR | The dose of UFH adhered to the standard institutional practice. An activated clotting time (ACT) target ≥250 seconds was recommended. All wires, catheters, and sheaths were to be flushed with heparinized saline. |
| Standard of Care: Heparins with Optional GPI | ACTIVE_COMPARATOR | Standard-of-care anti-thrombotic therapy as outlined in the European Society of Cardiology Dosing Guidelines for Management of STE-ACS, not including bivalirudin: UFH (100 international units/kg \[IU/kg\] without GPI and 60 IU/kg with GPI). Any of the following approved GPIs were used either as a routine strategy or as a bail out: eptifibatide (two 180-micrograms/kilogram \[μg/kg\] IV boluses with a 10-minute \[min\] interval followed by an infusion of 2.0 μg/kg/min for 72-96 hours); tirofiban (25 μg/kg followed by an infusion of 0.15 μg/kg/min for 18-24 hours); or abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min for 12-24 hours \[maximum dose of 10 μg/min\]). For this study, the control consisted of treatment with UFH or low molecular weight heparin (LMWH) with or without GPI and is referred to as "heparins with optional GPI." |
| Heparin | ACTIVE_COMPARATOR | unfractionated heparin will be administered as per institutional practice |
| Angiomax | EXPERIMENTAL | 1.0 mg/kg IV bolus followed by a 2.5 mg/kg/hr IV infusion |
| heparin/protamine | ACTIVE_COMPARATOR | 1.5-3.5 mg/kg (200-400 U/kg) intravenous (IV) bolus to target an ACT \>300 seconds followed by weight-adjusted boluses as needed during the procedure to achieve/maintain the target ACT. Protamine as needed |
| Name | Type | Description |
|---|---|---|
| Bivalirudin | DRUG | Bivalirudin is an anticoagulant that binds directly to thrombin in a bivalent and reversible fashion. |
| Unfractionated Heparin | DRUG | Unfractionated heparin is an anticoagulant. |
| Heparin | DRUG | - |
| Angiomax (bivalirudin) | DRUG | 250 mg vial administered as 1.0 mg/kg intravenous (IV) bolus and 2.5 mg/kg/h IV infusion during the procedure with the option to administer additional 0.1 to 0.5 mg/kg boluses to increase the level of anticoagulation as clinically indicated. A low-dose infusion could have been administered in the preoperative phase (up to 48 hours before the procedure) and in the postoperative phase (up to 14 days after the procedure) as clinically indicated for management of HIT/TS. A starting bolus of 0.1 mg/kg and/or an infusion of 0.2 mg/kg/h titrated to a desired activated partial thromboplastin time (aPTT), eg, 1.5-2.5 times baseline aPTT, was recommended. |
| Protamine | DRUG | Per institutional practice. Batches from hospital stock. |
Inclusion Criteria: * Males and females, ≥18 years of age * High risk (Euroscore ≥18, or considered inoperable) for surgical aortic valve replacement * Undergoing TAVR via transfemoral arterial access * Provide written informed consent before initiation of any study related procedures Exclusion Cr...
Bivalirudin is a small molecule anticoagulant developed by Novartis AG (ticker NVS). It is being studied in cardiovascular conditions including acute coronary syndrome, cardiac surgery, heparin-induced thrombocytopenia, and severe aortic stenosis. It is an investigational therapy in Phase 3 clinical development.
Bivalirudin targets F2, also known as coagulation factor II or thrombin. It acts as an inhibitor of this target. By inhibiting thrombin, bivalirudin interferes with the coagulation cascade that drives clot formation, which is the basis for its use as an anticoagulant in cardiovascular procedures and acute coronary syndrome.
Bivalirudin is being studied as an anticoagulant for patients with acute coronary syndrome. The Phase 3 European Ambulance Acute Coronary Syndrome Angiography Trial, NCT01087723, enrolled 2,198 participants with acute coronary syndrome across nine European countries. The trial is completed. Bivalirudin remains investigational for this indication.
Novartis AG, which trades under the ticker NVS, is the developer of bivalirudin. The company is responsible for the clinical development program covering acute coronary syndrome, cardiac surgery, cardiology, cardiovascular disease, heparin-induced thrombocytopenia, and severe aortic stenosis.
Bivalirudin is in Phase 3 clinical development. It is an investigational small molecule and is not described as approved. Its Phase 3 program includes trials in acute coronary syndrome and in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis, along with earlier-phase work in pediatric cardiology and cardiopulmonary bypass.
Bivalirudin has been studied in completed trials including NCT01651780, a Phase 3 open-label randomized trial in participants undergoing TAVR for severe aortic stenosis with 803 enrolled, and NCT01087723, a Phase 3 trial in acute coronary syndrome with 2,198 enrolled. Other completed studies include NCT00503126 in pediatric cardiology and NCT00079586 in cardiopulmonary bypass.