Acute Ischemic StrokePhase 2PAIR-TAVINCT05145283
Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation
A Phase 2 study testing Conestat alfa (Ruconest®) and NaCl 0.9%) in people with Acute Ischemic Stroke and Acute Renal Injury, run by University Hospital, Basel, Switzerland at 2 sites in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Ischemic Stroke, Acute Renal Injury
- What is being tested?
- Conestat alfa (Ruconest®) and NaCl 0.9%)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 141 participants
- Where
- 2 sitesSwitzerland
- Study dates
- 16 Mar 2022to 5 Jan 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent as documented by signature
- Severe AS and scheduled for transfemoral TAVI
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Switzerland2 sites
University Hospital Basel, Division of Internal Medicine
Basel, 4031
Stadtspital Triemli Zürich, Division of Cardiology
Zurich, 8063
About this study
Official 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.
Read the 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.
- Conditions
- Acute Ischemic Stroke, Acute Renal Injury
- Being tested
- Conestat alfa (Ruconest®), NaCl 0.9%)
- Keywords
- 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
- Medical subject headings
- Ischemic Stroke, Acute Kidney Injury, Aortic Valve Stenosis, Heart Valve Diseases, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conestat alfa (Ruconest®)Drug
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.
NaCl 0.9%)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Conestat alfa (Ruconest®) intervention group | Active comparator | 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). Receives: Drug: Conestat alfa (Ruconest®) |
| saline injection placebo group | Placebo comparator | 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. Receives: Drug: NaCl 0.9%) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: on day 4 (+/-1 day) after transfemoral TAVI
Secondary outcomes (13)
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)
Measured: on day 4 (+/-1 day) after transfemoral TAVI
Number of new cerebral ischemic lesions as measured by MRI
Number of new cerebral ischemic lesions as measured by MRI
Measured: on day 4 (+/-1 day) after transfemoral TAVI
Number (incidence) of clinically manifest ischemic stroke
Number (incidence) of clinically manifest ischemic stroke
Measured: within 48 hours after TAVI
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)
Measured: 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)
Change in secondary infarct growth at 3-months follow-up (defined as the difference between the infarct volumes)
Measured: at day 4 and at 3-months
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)
Measured: at 3 months
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.
Measured: at baseline and at 3-months follow-up
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)
Measured: at baseline and at 3-months follow-up
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.
Measured: at baseline and at 3-months follow-up
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
Measured: 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)
Incidence of AKI defined according to the Kidney Disease: Improving Global Outcomes criteria (any stage)
Measured: within 3 days after TAVI
Peak increase of urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL)
Peak increase of urinary NGAL (surrogate marker of acute renal injury)
Measured: within 48 hours after TAVI
Incidence of significant increase in serum cystatin C (>10%)
Incidence of significant increase in serum cystatin C (>10%)
Measured: within 48 hours after TAVI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2021
- Study start16 Mar 2022
- Primary completion5 Jan 2026
- Study completion5 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized in two parallel groups to receive either conestat alfa or placebo.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 141 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation, Pharming Technologies B.V.
- Responsible party
- Sponsor
- Investigators
- Michael Osthoff, Prof. Dr. med., Principal investigator, University Hospital Basel, Division of Internal MedicineRaban Jeger, Prof. Dr. med., Principal investigator, Stadtspital Triemli Zürich, Division of Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05145283
- Sponsor's protocol ID
- 2021-02025; me19Osthoff
- Acronym
- PAIR-TAVI
- Status last verified
- Apr 2026
- First submitted
- 17 Nov 2021
- Last updated
- 22 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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).
- ClinicalTrials.gov ID
- NCT05145283
- Acronym / sponsor ID
- PAIR-TAVI / 2021-02025; me19Osthoff
- Conditions
- Acute Ischemic Stroke, Acute Renal Injury
- Keywords
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation, Pharming Technologies B.V.
- Study start
- 16 Mar 2022 (actual)
- Primary completion
- 5 Jan 2026 (actual)
- Study completion
- 5 Jan 2026 (actual)
- First posted
- 6 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Patients will be randomized in two parallel groups to receive either conestat alfa or placebo.
| Arm | Type | Receives |
|---|---|---|
| Conestat alfa (Ruconest®) intervention group | Active comparator | Drug: Conestat alfa (Ruconest®)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). |
| saline injection placebo group | Placebo comparator | Drug: NaCl 0.9%)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Informed consent as documented by signature
- Severe AS and scheduled for transfemoral TAVI
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Conestat alfa (Ruconest®) intervention group |
| 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. | Drug | saline injection placebo group |
Primary outcome
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)
13 secondary outcomes
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
Number of new cerebral ischemic lesions as measured by MRI
Time frame: on day 4 (+/-1 day) after transfemoral TAVI
Number (incidence) of clinically manifest ischemic stroke
Time frame: 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
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
Total brain damage (defined as the sum of secondary brain atrophy and final infarct volume)
Time frame: at 3 months
Change in National Institutes of Health Stroke Scale Score (NIHSS)
Time frame: 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 trail making test
Time frame: 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
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
Peak increase of urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL)
Time frame: within 48 hours after TAVI
Incidence of significant increase in serum cystatin C (>10%)
Time frame: within 48 hours after TAVI
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Osthoff, Prof. Dr. med. principal investigator
University Hospital Basel, Division of Internal Medicine
Raban Jeger, Prof. Dr. med. principal investigator
Stadtspital Triemli Zürich, Division of Cardiology
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Conestat alfa (Ruconest®) and NaCl 0.9%) in people with Acute Ischemic Stroke and Acute Renal Injury, run by University Hospital, Basel, Switzerland at 2 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total volume of new cerebral ischemic lesions as evaluated by magnetic resonance imaging (MRI) (time frame: on day 4 (+/-1 day) after transfemoral TAVI). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2026; AzTrials last refreshed its copy on 7 Nov 2026.