Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation
Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation: a Multi-center, Randomized, Double-blind, Placebo-controlled Investigational Study (PAIR-TAVI).
University Hospital, Basel, Switzerland
250 participants
Mar 16, 2022
INTERVENTIONAL
Conditions
Summary
The aim of this trial is to assess the safety and efficacy of conestat alfa (Ruconest®, Pharming Technologies B.V.) on renal and cerebral ischemic events in patients undergoing TAVI for severe symptomatic aortic stenosis (AS) compared to placebo.
Eligibility
Inclusion Criteria2
- Informed consent as documented by signature
- Severe AS and scheduled for transfemoral TAVI
Exclusion Criteria15
- 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
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Interventions
In the current study, participants will receive two intravenous injections of conestat alfa (immediately during the TAVI procedure and again 3h later) at a dose of 100 U/kg (first dose) and of 50 U/kg (subsequent dose), for patients less than 84 kg; two intravenous injections (immediately during the TAVI procedure and again 4h later) of conestat at a dose of 8400 U (4 vials, first dose) and of 4200 U (2 vials, subsequent dose) for patients of 84 kg body weight or greater. The chosen regimen including repeated administration should increase and maintain serum C1INH levels above twice the serum concentration for six to eight hours in the majority of patients. The timeframe of therapeutic concentrations will cover the period of the TAVI procedure itself and the immediate postprocedural period during which reperfusion and additional ischemic events related to global hypoperfusion may occur.
Normal saline (NaCl 0.9%) will serve as placebo treatment. The respective amount of saline (according to patient weight matching the volume of conestat alfa that would have been used for this patient) will be withdrawn in an opaque syringe for slow IV injection.
Locations(2)
View Full Details on ClinicalTrials.gov
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NCT05145283