Stroke
Conditions
Brief summary
The purpose of this First-in-Human study is to evaluate the safety of using the Clotild® system to guide the endovascular thrombectomy (EVT) device to the clot location during EVT for the treatment of an acute ischemic stroke eligible to EVT, whatever the EVT device chosen. A secondary purpose is to assess the clinical performance, defined as the feasibility of measuring clot electrophysiological parameters in vivo during EVT procedures.
Detailed description
Clotild® is a neurovascular guidewire equipped with the Sensome proprietary impedance sensor. The latter allows the measurement of the electrophysiological characteristics of the surrounding tissues. Clotild® could categorize the thrombus occluding the cerebral blood vessel, and support the neurointerventionist during mechanical thrombectomy for the treatment of ischemic stroke. The aim of the study is to evaluate the safety and the performance of the device. The electrophysiological measurements will be used to update Clotild®'s database and thus improve the prediction accuracy of the model in providing physicians with insights for mechanical thrombectomy.
Interventions
DEVICEClotild® Smart Guidewire System (CSGS)
Use of Clotild® Smart Guidewire System as neurovascular guidewire
Sponsors
Sensome
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke eligible for EVT 2. M1 and/or MCA bifurcation arterial occlusion on Computed tomography angiography (CTA) or MRA (Magnetic resonance angiography) of an intracranial vessel amenable to EVT 3. Informed Consent by subject, subject's Legally Authorized Representative (LAR) or anyone approved by the Ethics Committee (EC) and/or regulatory agencies to provide consent on behalf of the subject.
Exclusion criteria
1. Patient having an intracranial occlusion other than M1 and/or MCA bifurcation, especially tandem occlusion and ICA (internal carotid artery) occlusion. 2. Current participation in another investigational device or drug study that has not completed the primary endpoint or that clinically interferes with the current study endpoints 3. Candidates not eligible for EVT based on neurointerventionist and/or neurologist investigators' opinion 4. Pregnancy or lactating subjects
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Patients Having Intracranial Vessel Perforation and / or Dissection Due to Clotild® Usage at the Site of Usage in Intracranial Vessels | Measured during the procedure and up to 24hr follow-up (when the 24hr images are taken) | Tthe proportion of patients having intracranial vessel perforation and / or dissection due to Clotild® usage at the site of usage in intracranial vessels will be assessed by Interventional Neuroradiologist during the procedure and final adjudication of the DSA (Digital Subtraction Angiography) by the Data Safety Monitoring Board. |
| The Ability to Perform Binary Classification of Individual Electrophysiological Parameter Measurements by Distinguishing Local Regions With Substantial Versus Negligible RBC Content in the Occlusion | Measurements taken by the investigator during the study procedure (insertion of the study device till removal from subject) | * The performance of the CSGS model will be assessed by the performance metric Area Under the Receiver Operator Characteristic curve (AUC of ROC) computed from the RBC-content score predicted on the validation dataset only. * The ROC curve will be defined by the sensitivity (true positive rate) on the Y-axis and 1- specificity (false positive rate) on the X-axis. The ground truth is defined as the binary classification of the local regions into RBC-positive or RBC-negative content performed by SENSOME experts. * The comparator will be the binary classification score determined by the CSGS model. The CSGS model will be developed using interventions from the development phase (Development Performance Population) while it will be validated on the impedance data from the validation phase (Local-Scale Performance Population). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1. The Concordance Between Aggregated Occlusion Measurements (Clot-scale) Done by CSGS, and the Histology (i.e., Histopathology) Results of the Clot Retrieved During the EVT Procedure, Regarding Red Blood Cell Content in the Occlusion, | Occlusion Measurements taken by the investigator during the study procedure (insertion of the study device till removal from subject). Clot retrieved few minutes after study procedure ended. | This endpoint evaluated the clot-scale predicted RBC% as compared to histological evaluation of RBC%. The analyzed dataset comprised the interventions from the clot-scale validation performance population for which at least one tagged measurement was predicted with clot contact. The concordance is to be evaluated by the slope of the linear regression of the independent variable "RBC percentage predicted at clot scale" against the dependent variable "RBC percentage measured by histology". No additional factors or covariates were included when assessing the linear regression. |
| 2. The Ability of CSGS to Detect the Proximal End of the Occlusion (Sensor-scale), as Compared to the Physician's Labelling (Tag 'PRE CLOT' for no Occlusion Contact and Tag 'CLOT' for Occlusion Contact), | Measurements taken by the investigator during the first few minutes of the study procedure | This endpoint sought to evaluate the ability of study device (CSGS) to detect the proximal end of the occlusion, as compared to the physician's labelling. The concordance was judged by the Area Under the Curve of Receiver Operating Characteristic (AUC of ROC) on the validation dataset. Evaluation included those interventions from the validation set where the 'PRE CLOT' and 'CLOT' tagged measurements were acquired with at most one missing or anomalous individual measurement |
| 3. Procedural Success Defined as the Ability to Navigate CSGS to the Occlusion Site and Measure Electrophysiological Properties of the Occlusion, | Measurements taken by the investigator during the study procedure (insertion of the study device till removal from subject | Procedural success defined as the ability to navigate the investigational device to the occlusion and measure electrophysiological properties of the occlusion. Procedural success was achieved from the moment that at least one evaluable measurement in the occlusion was captured by the investigational device. |
| 4. The Ability to Perform Binary Classification of Individual Electrophysiological Parameter Measurements (Local-scale) by Distinguishing Local Regions With Substantial Platelet Content From Regions With Negligible Platelet Content in the Occlusion, | Measurements taken by the investigator during the study procedure (insertion of the study device till removal from subject | The ability to perform binary classification was evaluated by the performance metric AUC of ROC (Area under the Curve of Receiver Operating Characteristic) computed from the platelet-content score predicted on the validation dataset. The same methodology was used as for the primary performance endpoint. |
| 5. The Concordance Between Aggregated Occlusion Measurements (Clot-scale) Done by CSGS, and the Histology Results of the Clot Retrieved During the EVT Procedure, Regarding Platelet Content in the Occlusion, | Occlusion Measurements taken by the investigator during the study procedure (insertion of the study device till removal from subject). Clot retrieved few minutes after study procedure ended. | This endpoint evaluated the clot-scale predicted platelet content as compared to histological evaluation (CD42b immunostaining). The analysis was performed using the clot-scale validation performance population. * To determine the histological results of the clot, the platelet % composition (value between 0 and 100) was averaged over the 3 analyzed slides provided by the Core Laboratory. * Significant correlation was judged at the 0.05 significance level by the t-statistic of the linear coefficient of the ordinary linear regression between the independent variable "platelet % content as output by the prediction model" and the dependent variable "platelet % content as quantified by the IHC CD42b immunochemistry staining histological analysis". A complimentary analysis was carried out considering the MSB 'Platelets and other' percentage quantification provided by the histology core lab. No additional factors or covariates were included when assessing the linear regression |
| 6. The Ability to Perform Binary Classification of Individual Electrophysiological Parameter Measurements (Local-scale) by Distinguishing Local Regions With Substantial Fibrin Content From Regions With Negligible Fibrin Content in the Occlusion, | Measurements taken by the investigator during the study procedure (insertion of the study device till removal from subject) | The ability to perform binary classification was evaluated by the performance metric AUC of ROC (Area Under the Curve of Receiver Operating Characteristic) computed from the platelet-content score predicted on the validation dataset. The same methodology was used as for the primary performance endpoint. |
| 7. The Concordance Between Aggregated Occlusion Measurements (Clot-scale) Done by CSGS, and the Histology Results of the Clot Retrieved During the EVT Procedure, Regarding Fibrin Content in the Occlusion. | Occlusion Measurements taken by the investigator during the study procedure (insertion of the study device till removal from subject). Clot retrieved few minutes after study procedure ended. | This endpoint evaluated the clot-scale predicted fibrin content as compared to histological evaluation (MSB staining), using the clot-scale validation performance population. * To determine the histological results of the clot, the fibrin percentage composition (value between 0 and 100) was averaged over the 3 analyzed slides provided by the core lab. * Significant correlation was judged at the 0.05 significance level by the t-statistic of the linear coefficient of the ordinary linear regression between the independent variable "fibrin percentage content as output by the prediction model" and the dependent variable "fibrin percentage content as quantified by the MSB-staining histological analysis". No additional factors or covariates were included when assessing the linear regression. |
Countries
Australia, France
Contacts
PRINCIPAL_INVESTIGATORAndrew Cheung, MD
Liverpool Hospital, Liverpool NSW, Australia
PRINCIPAL_INVESTIGATORDennis Cordato, MD
Liverpool Hospital, Liverpool NSW, Australia
Participant flow
Recruitment details
FPI: 6-AUG-2021 LPO: 16-APR-2024. Of the 45 enrolled subjects, four screen failures were documented yielding a safety population (treated population) of 41 individuals. Of those, two subjects did not provide full consent, resulting in 39 individuals within the per-protocol population
Pre-assignment details
Eligibility check is in 2 steps - at the time of screening (and consenting), few patients got medication to resolve the clot. As the study device's purpose is to evaluate clot composition, a 2nd eligibility check is done just prior the study procedure - 4 patients did not meet this additional check. In France in emergency cases - regulations allow that consent is taken after the procedure. Two subjects did not provide it. Only safety data collected in these 2 subjects, no performance data
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 75.4 years |
| Alcohol consumption Current user | 10 Participants |
| Alcohol consumption Missing | 2 Participants |
| Alcohol consumption Never used | 14 Participants |
| Alcohol consumption Not documented | 11 Participants |
| Alcohol consumption No use within the last 12 months | 2 Participants |
| Arrhythmia NO | 23 Participants |
| Arrhythmia YES | 16 Participants |
| Blood Pressure Grade 1 hypertension (SBP between 140-159 mmHg and/or DBP between 90-99 mmHg) | 10 Participants |
| Blood Pressure Grade 2 hypertension (SBP between 160-179 mmHg and/or DBP between 100-109 mmHg) | 5 Participants |
| Blood Pressure Grade 3 hypertension (SBP ≥180 and/or DBP ≥110 mmHg) | 6 Participants |
| Blood Pressure High-normal (SBP between 130-139 mmHg and/or DBP between 85-89 mmHg) | 8 Participants |
| Blood Pressure Missing | 1 Participants |
| Blood Pressure Normal (SBP between 120-129 mmHg and/or DBP between 80-84 mmHg) | 5 Participants |
| Blood Pressure Optimal (SBP <120 mmHg and DBP <80 mmHg) | 4 Participants |
| BMI Missing | 12 Participants |
| BMI Normal weight (18.5≤BMI<25 kg/m2) | 12 Participants |
| BMI Obese (BMI≥30 kg/m2) | 7 Participants |
| BMI Overweight (25≤BMI<30 kg/m2) | 7 Participants |
| BMI Underweight (BMI<18.5 kg/m2) | 1 Participants |
| COPD NO | 35 Participants |
| COPD YES | 4 Participants |
| Coronary Artery Disease NO | 34 Participants |
| Coronary Artery Disease YES | 5 Participants |
| Diabetes NO | 31 Participants |
| Diabetes YES | 8 Participants |
| Dislipidemia NO | 31 Participants |
| Dislipidemia Yes | 8 Participants |
| ECG results Abnormal - clinically significant | 9 Participants |
| ECG results Abnormal - not clinically significant | 11 Participants |
| ECG results Missing | 6 Participants |
| ECG results Normal | 13 Participants |
| GCS >10 | 30 Participants |
| GCS 8-10 | 5 Participants |
| GCS Missing | 4 Participants |
| NIHSS Minor stroke (1-4) | 2 Participants |
| NIHSS Missing | 1 Participants |
| NIHSS Moderate stroke (5-15) | 18 Participants |
| NIHSS Moderate to severe stroke (16-20) | 10 Participants |
| NIHSS Severe stroke (21-42) | 8 Participants |
| Previous hemorrhagic stroke NO | 38 Participants |
| Previous hemorrhagic stroke YES | 1 Participants |
| Previous ischemic stroke / TIA NO | 32 Participants |
| Previous ischemic stroke / TIA YES | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Region of Enrollment Australia | 33 participants |
| Region of Enrollment France | 12 participants |
| Renal Dysfunction NO | 35 Participants |
| Renal Dysfunction YES | 4 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 19 Participants |
| Smoking Current user | 4 Participants |
| Smoking Missing | 1 Participants |
| Smoking Never used | 20 Participants |
| Smoking Not documented | 6 Participants |
| Smoking No use within the last 10 years | 3 Participants |
| Smoking No use within the last 12 months | 5 Participants |
| Thrombolytic medication NO | 25 Participants |
| Thrombolytic medication YES | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 41 |
| other Total, other adverse events | 9 / 41 |
| serious Total, serious adverse events | 11 / 41 |
Outcome results
None listed