Acute Ischemic Stroke Clinical Trial
— PAIR-TAVIOfficial 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).
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.
Status | Recruiting |
Enrollment | 250 |
Est. completion date | March 2025 |
Est. primary completion date | March 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Switzerland | University Hospital Basel, Division of Internal Medicine | Basel | |
Switzerland | Stadtspital Triemli Zürich, Division of Cardiology | Zürich |
Lead Sponsor | Collaborator |
---|---|
University Hospital, Basel, Switzerland | Pharming Technologies B.V., Swiss National Science Foundation |
Switzerland,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Persistent renal impairment after 3 months (defined as increase in serum creatinine of at least 50% from baseline at 3 months) | Persistent renal impairment after 3 months (defined as serum creatinine increase of at least 50% from baseline at 3 months) | at 3-months follow-up | |
Other | Change in concentration of C1-Esterase-Inhibitor (C1INH) | Change in concentration of C1INH | during the first 24 hours after TAVI | |
Other | Change in troponin T to assess myocardial injury following TAVI | Change in troponin T to assess myocardial injury following TAVI | within 72 hours after TAVI | |
Other | Change in urinary biomarkers of renal injury (Kidney Injury Molecule-1 (KIM-1) and osteopontin) | Change in urinary biomarkers of renal injury (Kidney Injury Molecule-1 (KIM-1) and osteopontin) | within 48 hours after TAVI | |
Other | Change in serum neurofilament light chain (marker of neuroaxonal damage) | Change in serum neurofilament light chain (marker of neuroaxonal damage) | within 3 months after TAVI | |
Other | Number of adverse events | Number of adverse events | within 3 months after TAVI | |
Other | Number of serious adverse events | Number of serious adverse events | within 3 months after TAVI | |
Other | Number of major cardiovascular and renal events (cardiovascular death, non-fatal myocardial infarction, heart failure hospitalization, stroke, dialysis) | Number of major cardiovascular and renal events (cardiovascular death, non-fatal myocardial infarction, heart failure hospitalization, stroke, dialysis) | within 3 months after TAVI | |
Other | Number of complications of transfemoral TAVI | Number of complications of transfemoral TAVI such as conduction disturbance (including permanent pacemaker implantation) or aortic regurgitation according to the Valve Academic Research Consortium (VARC)-3 criteria, or bleeding according to the Bleeding Academic Research Consortium (BARC)-criteria) | within 3 months after TAVI | |
Primary | Total volume of new cerebral ischemic lesions as evaluated by magnetic resonance imaging (MRI) | Total volume of new cerebral ischemic lesions as evaluated by magnetic resonance imaging (MRI) | on day 4 (+/-1 day) after transfemoral TAVI | |
Secondary | Maximum new lesion volume as measured by MRI (i.e. volume of the largest new lesion) | Maximum new lesion volume as measured by MRI (i.e. volume of the largest new lesion) | on day 4 (+/-1 day) after transfemoral TAVI | |
Secondary | Number of new cerebral ischemic lesions as measured by MRI | Number of new cerebral ischemic lesions as measured by MRI | on day 4 (+/-1 day) after transfemoral TAVI | |
Secondary | Number (incidence) of clinically manifest ischemic stroke | Number (incidence) of clinically manifest ischemic stroke | within 48 hours after TAVI | |
Secondary | Change in secondary brain atrophy at 3-months follow-up | Secondary brain atrophy at 3-months follow-up related to the gradual cellular loss as measured by high resolution 3D T1-weighted MR images (defined as the difference between the brain volumes) | at baseline and at 3-months follow-up | |
Secondary | Change in secondary infarct growth at 3-months follow-up (defined as the difference between the infarct volumes) | Change in secondary infarct growth at 3-months follow-up (defined as the difference between the infarct volumes) | at day 4 and at 3-months | |
Secondary | Total brain damage (defined as the sum of secondary brain atrophy and final infarct volume) | Total brain damage (defined as the sum of secondary brain atrophy and final infarct volume) | at 3 months | |
Secondary | Change in National Institutes of Health Stroke Scale Score (NIHSS) | The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. | at baseline and at 3-months follow-up | |
Secondary | Change in modified Rankin scale | Change in modified Rankin scale; scale runs from 0-6, running from perfect health (0) without symptoms to death (6) | at baseline and at 3-months follow-up | |
Secondary | Change in trail making test | Change in trail making test; scoring is based on time taken to complete the test (e.g. 35 seconds yielding a score of 35) with lower scores being better. | at baseline and at 3-months follow-up | |
Secondary | Change in Montreal Cognitive Assessment test (MOCA) | Montreal Cognitive Assessment test scores range between 0 and 30. A score of 26 or over is considered to be normal | at baseline and at 3-months follow-up | |
Secondary | Incidence of acute kidney injury (AKI) defined according to the Kidney Disease: Improving Global Outcomes criteria (any stage) | Incidence of AKI defined according to the Kidney Disease: Improving Global Outcomes criteria (any stage) | within 3 days after TAVI | |
Secondary | Peak increase of urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) | Peak increase of urinary NGAL (surrogate marker of acute renal injury) | within 48 hours after TAVI | |
Secondary | Incidence of significant increase in serum cystatin C (>10%) | Incidence of significant increase in serum cystatin C (>10%) | within 48 hours after TAVI |
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