Randomized, double-blind, placebo-controlled study to assess the efficacy and safety of Conestat alfa regarding the occurrence of circulatory disorders in the brain and kidneys after percutaneous aortic valve replacement.
Summary description of the study
In this study, patients suffering from severe aortic stenosis who are undergoing aortic valve replacement (TAVI) will be included. During aortic valve replacement, unnoticed circulatory disorders in the brain and kidneys may occur, among other things, due to tiny calcified fragments that can detach from the calcified heart valve. These resulting circulatory disorders lead to an inflammatory response that causes additional tissue damage. So far, there are no medications that can reduce circulatory disorders and their consequences. Conestat alfa is an artificially produced body protein (human C1 inhibitor) that inhibits various inflammatory systems in the body. It has not yet been studied in patients with aortic valve stenosis. In an animal model, it was able to reduce the consequences of a circulatory disorder in the brain and kidneys. Furthermore, there are initial indications that this medication might also have a positive effect on kidney function in humans after circulatory disorders. In our research project, we want to find out whether Conestat alfa can reduce the extent of circulatory disorders in the brain and kidneys after TAVI. To this end, kidney function and the extent of the circulatory disorder will be measured in the MRI of the head at three different time points.
(BASEC)
Intervention under investigation
The study drug Conestat alfa (Ruconest®) is being investigated. Conestat alfa is an artificially produced body protein that is approved in Europe and the USA for a rare genetic disease (C1 inhibitor deficiency). The study medication will be administered twice, once during the TAVI and once 3 hours after the first dose. The study is randomized and double-blind, meaning that participants are randomly assigned to one of two groups. One group receives the investigational substance (Conestat alfa), while the other group (the control) receives a saline solution (the placebo).
(BASEC)
Disease under investigation
The study is conducted in patients with severe aortic valve stenosis (aortic stenosis) who are undergoing aortic valve replacement.
(BASEC)
1. Informed consent, documented with the patient's signature and date 2. Age ≥ 18 years 3. Severe aortic stenosis and planned transfemoral aortic valve replacement (TAVI)
(BASEC)
Exclusion criteria
1. Hemodynamic instability requiring emergency TAVI 2. Pregnancy or breastfeeding 3. Rabbit allergy
(BASEC)
Trial sites
Basel, Zurich
(BASEC)
Sponsor
Universitätsspital Basel
(BASEC)
Contact
Contact Person Switzerland
Michael Osthoff
+41 61 328 5420
Michael.Osthoff@clutterusb.chUniversity Hospital Basel, Basel, Switzerland
(BASEC)
General Information
University Hospital Basel, Division of Internal Medicine,Stadtspital Triemli Z?rich, Division of Cardiology,
+41 61 328 54 20
Michael.Osthoff@clutterusb.ch(ICTRP)
General Information
University Hospital Basel, Division of Internal MedicineStadtspital Triemli Zrich, Division of Cardiology
+41 61 328 54 20
Michael.Osthoff@clutterusb.ch(ICTRP)
General Information
University Hospital Basel, Division of Internal MedicineStadtspital Triemli Zrich, Division of Cardiology
(ICTRP)
Scientific Information
University Hospital Basel, Division of Internal Medicine,Stadtspital Triemli Z?rich, Division of Cardiology,
+41 61 328 54 20
Michael.Osthoff@clutterusb.ch(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee northwest/central Switzerland EKNZ
(BASEC)
Date of authorisation
30.11.2021
(BASEC)
ICTRP Trial ID
NCT05145283 (ICTRP)
Official title (approved by ethics committee)
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). (BASEC)
Academic title
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). (ICTRP)
Public title
Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation (ICTRP)
Disease under investigation
Acute Ischemic StrokeAcute Renal Injury
(ICTRP)
Intervention under investigation
Drug: Conestat alfa (Ruconest)Drug: NaCl 0.9%)
(ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Double (Participant, Investigator).
(ICTRP)
Inclusion/Exclusion 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
(ICTRP)
not available
Primary and secondary end points
Total volume of new cerebral ischemic lesions as evaluated by magnetic resonance imaging (MRI)
(ICTRP)
Maximum new lesion volume as measured by MRI (i.e. volume of the largest new lesion);Number of new cerebral ischemic lesions as measured by MRI;Number (incidence) of clinically manifest ischemic stroke;Change in secondary brain atrophy at 3-months follow-up;Change in secondary infarct growth at 3-months follow-up (defined as the difference between the infarct volumes);Total brain damage (defined as the sum of secondary brain atrophy and final infarct volume);Change in National Institutes of Health Stroke Scale Score (NIHSS);Change in modified Rankin scale;Change in trail making test;Change in Montreal Cognitive Assessment test (MOCA);Incidence of acute kidney injury (AKI) defined according to the Kidney Disease: Improving Global Outcomes criteria (any stage);Peak increase of urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL);Incidence of significant increase in serum cystatin C (>10%)
(ICTRP)
Registration date
17.11.2021 (ICTRP)
Incorporation of the first participant
not available
Secondary sponsors
Swiss National Science Foundation;Pharming Technologies B.V. (ICTRP)
Additional contacts
Michael Osthoff, Prof. Dr. med.;Raban Jeger, Prof. Dr. med.;Michael Osthoff, Prof. Dr. med., michael.osthoff@usb.ch, +41 61 328 54 20, University Hospital Basel, Division of Internal Medicine,Stadtspital Triemli Z?rich, Division of Cardiology, (ICTRP)
Secondary trial IDs
2021-02025, me19Osthoff (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT05145283 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available