Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation (PAIR-TAVI)
Acute Ischemic Stroke, Acute Renal Injury
About this trial
This is an interventional prevention trial for Acute Ischemic Stroke focused on measuring Severe aortic stenosis (AS), Valvular heart disease, Transcatheter aortic valve implantation (TAVI), cerebral embolic events, renal embolic events, Ischemia/reperfusion injury (IRI), recombinant human C1 esterase inhibitor (rhC1INH, conestat alfa), complement system, contact activation system
Eligibility Criteria
Inclusion Criteria:
- Informed consent as documented by signature
- Severe AS and scheduled for transfemoral TAVI
Exclusion Criteria:
- Contraindications to the class of drugs under study (C1INH), e.g., known hypersensitivity or allergy to class of drugs or the investigational product
- History of allergy to rabbits (as rhC1INH is derived from the breast milk of transgenic rabbits)
- Women who are pregnant or breast feeding
- Hemodynamic instability requiring emergency TAVI
- Valve-in-valve procedure
- Other access route than transfemoral
- Non-cardiac co-morbidity with expected survival <6 months
- Ischemic or hemorrhagic stroke within 30 days before TAVI
- Dialysis or estimated glomerular filtration rate (eGFR) <20 ml/min/1.73m2
- Contraindication for MRI such as a permanent non-MRI compatible pacemaker or severe claustrophobia
- Liver cirrhosis (any Child-Pugh score)
- Incapacity or inability to provide informed consent
- Participation in another study with investigational drug or medical device within the 30 days preceding and during the present study
- Previous enrolment into the current study
- Any uncontrolled or significant concurrent illness that would put the patient at a greater risk or limit compliance with the study requirements at the discretion of the investigator
Sites / Locations
- University Hospital Basel, Division of Internal MedicineRecruiting
- Stadtspital Triemli Zürich, Division of CardiologyRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Placebo Comparator
Conestat alfa (Ruconest®) intervention group
saline injection placebo group
The intervention group will receive conestat alfa (Ruconest®) as a 10-minute slow intravenous injection (up to 56 ml) once during the TAVI procedure followed by a second administration (up to 28 ml) again three hours later. The first administration will include a dosage of 100 U/kg (maximum 8400 U) conestat alfa. The dosing of the second administration will be 50 U/kg (maximum 4200 U).
Subjects randomized into the placebo group will receive an intravenous normal saline injection with corresponding volume over 10 minutes during the TAVI procedure and three hours later after the first administration.