Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation (PAIR-TAVI)

April 20, 2026 updated by: University Hospital, Basel, Switzerland

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Severe aortic stenosis (AS) is a frequent valvular heart disease in the elderly with a prevalence of 4 to 10% and a mean survival of only 0.5 to 5 years if left untreated. Transcatheter aortic valve implantation (TAVI) has evolved as standard of care for high-, intermediate and potentially even low surgical risk candidates due to a lower perioperative risk compared to surgical aortic valve replacement (SAVR). Despite its relative safety compared to SAVR, embolic events originating from the calcified valve and leading to ischemic stroke and acute renal injury are major complications following TAVI in the acute and subacute period, and are associated with increased morbidity including cognitive decline and mortality. While cerebral embolic protection devices (CEPD) such as the Sentinel® CEPD (Boston Scientific) were designed to reduce the burden of cerebral embolic events, their impact on clinical events has yet to be determined, and other prophylactic options are currently not available. Ischemia/reperfusion injury (IRI) is a key pathophysiological mechanism involved in cerebral and renal embolic events after TAVI resulting in activation of endothelial cells, the contact activation and the complement system and attraction of neutrophils to the site of injury. In this regard, recombinant human C1 esterase inhibitor (rhC1INH, conestat alfa), a potent inhibitor of the complement and the contact system has been shown to reduce the size of cerebral ischemic damage and of renal injury in experimental IRI models, and has successfully been investigated in a pilot study of acute kidney injury following the administration of contrast media. The aim of the current 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 AS compared to placebo.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
141

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Switzerland
      • Basel, Switzerland, 4031
        • University Hospital Basel, Division of Internal Medicine
      • Zurich, Switzerland, 8063
        • Stadtspital Triemli Zürich, Division of Cardiology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Conestat alfa (Ruconest®) intervention 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).
Drug: Conestat alfa (Ruconest®)
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.
Placebo Comparator: saline injection placebo group
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.
Drug: NaCl 0.9%)
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Total volume of new cerebral ischemic lesions as evaluated by magnetic resonance imaging (MRI)
Time Frame: on day 4 (+/-1 day) after transfemoral TAVI
Total volume of new cerebral ischemic lesions as evaluated by magnetic resonance imaging (MRI)
on day 4 (+/-1 day) after transfemoral TAVI

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum new lesion volume as measured by MRI (i.e. volume of the largest new lesion)
Time Frame: on day 4 (+/-1 day) after transfemoral TAVI
Maximum new lesion volume as measured by MRI (i.e. volume of the largest new lesion)
on day 4 (+/-1 day) after transfemoral TAVI
Number of new cerebral ischemic lesions as measured by MRI
Time Frame: on day 4 (+/-1 day) after transfemoral TAVI
Number of new cerebral ischemic lesions as measured by MRI
on day 4 (+/-1 day) after transfemoral TAVI
Number (incidence) of clinically manifest ischemic stroke
Time Frame: within 48 hours after TAVI
Number (incidence) of clinically manifest ischemic stroke
within 48 hours after TAVI
Change in secondary brain atrophy at 3-months follow-up
Time Frame: at baseline and 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
Change in secondary infarct growth at 3-months follow-up (defined as the difference between the infarct volumes)
Time Frame: at day 4 and at 3-months
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
Total brain damage (defined as the sum of secondary brain atrophy and final infarct volume)
Time Frame: at 3 months
Total brain damage (defined as the sum of secondary brain atrophy and final infarct volume)
at 3 months
Change in National Institutes of Health Stroke Scale Score (NIHSS)
Time Frame: at baseline and at 3-months follow-up
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
Change in modified Rankin scale
Time Frame: at baseline and at 3-months follow-up
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
Change in trail making test
Time Frame: at baseline and at 3-months follow-up
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
Change in Montreal Cognitive Assessment test (MOCA)
Time Frame: at baseline and at 3-months follow-up
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
Incidence of acute kidney injury (AKI) defined according to the Kidney Disease: Improving Global Outcomes criteria (any stage)
Time Frame: within 3 days after TAVI
Incidence of AKI defined according to the Kidney Disease: Improving Global Outcomes criteria (any stage)
within 3 days after TAVI
Peak increase of urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL)
Time Frame: within 48 hours after TAVI
Peak increase of urinary NGAL (surrogate marker of acute renal injury)
within 48 hours after TAVI
Incidence of significant increase in serum cystatin C (>10%)
Time Frame: within 48 hours after TAVI
Incidence of significant increase in serum cystatin C (>10%)
within 48 hours after TAVI

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Persistent renal impairment after 3 months (defined as increase in serum creatinine of at least 50% from baseline at 3 months)
Time Frame: at 3-months follow-up
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
Change in concentration of C1-Esterase-Inhibitor (C1INH)
Time Frame: during the first 24 hours after TAVI
Change in concentration of C1INH
during the first 24 hours after TAVI
Change in troponin T to assess myocardial injury following TAVI
Time Frame: within 72 hours after TAVI
Change in troponin T to assess myocardial injury following TAVI
within 72 hours after TAVI
Change in urinary biomarkers of renal injury (Kidney Injury Molecule-1 (KIM-1) and osteopontin)
Time Frame: within 48 hours after TAVI
Change in urinary biomarkers of renal injury (Kidney Injury Molecule-1 (KIM-1) and osteopontin)
within 48 hours after TAVI
Change in serum neurofilament light chain (marker of neuroaxonal damage)
Time Frame: within 3 months after TAVI
Change in serum neurofilament light chain (marker of neuroaxonal damage)
within 3 months after TAVI
Number of adverse events
Time Frame: within 3 months after TAVI
Number of adverse events
within 3 months after TAVI
Number of serious adverse events
Time Frame: within 3 months after TAVI
Number of serious adverse events
within 3 months after TAVI
Number of major cardiovascular and renal events (cardiovascular death, non-fatal myocardial infarction, heart failure hospitalization, stroke, dialysis)
Time Frame: within 3 months after TAVI
Number of major cardiovascular and renal events (cardiovascular death, non-fatal myocardial infarction, heart failure hospitalization, stroke, dialysis)
within 3 months after TAVI
Number of complications of transfemoral TAVI
Time Frame: within 3 months after 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Basel, Switzerland

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Swiss National Science Foundation
Pharming Technologies B.V.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Raban Jeger, Prof. Dr. med., Stadtspital Triemli Zürich, Division of Cardiology
  • Principal Investigator: Michael Osthoff, Prof. Dr. med., University Hospital Basel, Division of Internal Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 16, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 5, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 5, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 17, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 22, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 6, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2021-02025; me19Osthoff

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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