Periodic Reporting for period 1 - StrokeAlert- WomenEU (Striking Stroke- enhancing and expanding StrokeAlert’s business skills)
Periodo di rendicontazione: 2022-07-01 al 2023-06-30
A Stroke occurs every 2 seconds, Every fourth person will suffer one. A billion people are at risk. Over 15 million people a year will suffer from stroke.Stroke is the leading cause of disability worldwide and the main cause of disability. Timely intervention with thrombolysis cures ischemic stroke. It prevents irreversible neuronal death by effective revascularization. Most survivors remain with significant disabilities. Stroke is treatable and even avoidable if detected in time. Early detection improves outcomes, as every second 2milion cells die. Unfortunately, most individuals do not reach the care in time, resulting in a devastating outcome. The inability to detect clinical changes prevents proper diagnosis and timely treatment. With increasing longevity, preserving well-being is recognized as a global challenge (UNDP3 goal).
The current approach- Unable to detect stroke: Only 15-32% of patients presenting with treatable stroke arrive on time, and even among presumed eligible patients, treatment rates are low (25% - 43%). Current solutions include US Doppler devices that can be applied for these purposes while in hospital but require a technician to operate and are not continuous and, therefore, not widely used. Other solutions are BIS devices, which measure EEG signals, and NIRS (near Infrared spectroscopy) devices, which measure cerebral oxygenation. Both are continuous and easy to apply but do not directly detect a stroke. Imaging modalities can also be used- i.e. CT, MRI, the occurrence of stroke which shows directly the but is not bedside or accessible or continuous, thus are not utilized for these purposes. The main differentiation factors from existing products are (1) a simple responsive system and (2) a specific ability to alert stroke.
The current approach- Unable to detect stroke: Only 15-32% of patients presenting with treatable stroke arrive on time, and even among presumed eligible patients, treatment rates are low (25% - 43%). Current solutions include US Doppler devices that can be applied for these purposes while in hospital but require a technician to operate and are not continuous and, therefore, not widely used. Other solutions are BIS devices, which measure EEG signals, and NIRS (near Infrared spectroscopy) devices, which measure cerebral oxygenation. Both are continuous and easy to apply but do not directly detect a stroke. Imaging modalities can also be used- i.e. CT, MRI, the occurrence of stroke which shows directly the but is not bedside or accessible or continuous, thus are not utilized for these purposes. The main differentiation factors from existing products are (1) a simple responsive system and (2) a specific ability to alert stroke.
StrokeAlert previously completed a proof of concept study for our product AverttoTM (POC; model 101). Currently, there is an ongoing double-blind Hospital study to prove the value proving stroke detection in the relevant clinical arena (POV; model 201). Now initiating an R&D project to shift stroke monitoring from the hospital to the home arena and from a noninvasive to an insertable sensor (Validation of solution; model 301).
Previous milestones (for POC):
1. Sensor Development: AverttoTM transitioned from bimorph sensors to pressure sensors, utilizing a smaller wireless rechargeable controller.
2. Algorithm Development: AverttoTM has an initial threshold algorithm with high accuracy for detecting large vessel occlusion (LVO).
3. Clinical Studies:
Endovascular Clinical Study: StrokeAlert concluded a clinical study involving 50 patients across three clinical centers, namely Rabin, Galilee medical center, Israel, and VDH in Barcelona.
Rat Study: to assess the evolution of stroke over time.
Astronaut study: One of the 14 medical studies performed during the Axiom1 space mission. We monitored astronauts (n=4) for hemodynamic changes before and after a 17-day space mission to assess microgravity's impact on carotid hemodynamics.
4. Business Development (BD): StrokeAlert secured its first external investments and negotiated specific milestones for venture capital firms and institutional investors for future funding.
5. Regulation: StrokeAlert submitted a Qsub FDA submission for a breakthrough medical device in the USA. StrokeAlert received AEMPS registration(Spanish Agency of Medicines and Medical Devices) in Spain based on pilot data for future CE certification.
Avertto’s Ongoing POV:
1. Sensor development: improving the 2nd prototype (201 to 201.1).
2. Algorithm development Identifying and quantifying pulse wave quality and hemodynamic changes during large cerebral artery occlusion (LVO).
3. Multicenter Hospital double-blinded prospective study carotid monitoring for acute stroke-Assessment of hemodynamic changes for detecting large vessel occlusions (LVOs) in high-risk hospitalized patients.
4. Business development and marketing: Establishing strategic partnerships with Key Opinion Leaders (KOLs) at renowned institutions.
5. Existing Patents:
PCT/IL2021/051122 National phase US and IL; filed on 14-Sep-2021, on the system and method
US Provisional Patent Application No. 63/466,297, filed on 14-May-2023, includes algorithm and insertable sensors.
Previous milestones (for POC):
1. Sensor Development: AverttoTM transitioned from bimorph sensors to pressure sensors, utilizing a smaller wireless rechargeable controller.
2. Algorithm Development: AverttoTM has an initial threshold algorithm with high accuracy for detecting large vessel occlusion (LVO).
3. Clinical Studies:
Endovascular Clinical Study: StrokeAlert concluded a clinical study involving 50 patients across three clinical centers, namely Rabin, Galilee medical center, Israel, and VDH in Barcelona.
Rat Study: to assess the evolution of stroke over time.
Astronaut study: One of the 14 medical studies performed during the Axiom1 space mission. We monitored astronauts (n=4) for hemodynamic changes before and after a 17-day space mission to assess microgravity's impact on carotid hemodynamics.
4. Business Development (BD): StrokeAlert secured its first external investments and negotiated specific milestones for venture capital firms and institutional investors for future funding.
5. Regulation: StrokeAlert submitted a Qsub FDA submission for a breakthrough medical device in the USA. StrokeAlert received AEMPS registration(Spanish Agency of Medicines and Medical Devices) in Spain based on pilot data for future CE certification.
Avertto’s Ongoing POV:
1. Sensor development: improving the 2nd prototype (201 to 201.1).
2. Algorithm development Identifying and quantifying pulse wave quality and hemodynamic changes during large cerebral artery occlusion (LVO).
3. Multicenter Hospital double-blinded prospective study carotid monitoring for acute stroke-Assessment of hemodynamic changes for detecting large vessel occlusions (LVOs) in high-risk hospitalized patients.
4. Business development and marketing: Establishing strategic partnerships with Key Opinion Leaders (KOLs) at renowned institutions.
5. Existing Patents:
PCT/IL2021/051122 National phase US and IL; filed on 14-Sep-2021, on the system and method
US Provisional Patent Application No. 63/466,297, filed on 14-May-2023, includes algorithm and insertable sensors.
As proof of the validity and reliability of the company’s algorithms for the detection of large vessel occlusions (LVO), a multi-center open perspective study was performed. Skin displacement over the carotid artery was recorded using bimorph piezoelectric sensors (AverttoTM 101) during endovascular procedures. During these procedures, a balloon is inflated inside the artery creating a temporary occlusion. These recordings were then used to analyze the pulse waves in the signals and determine whether a difference could be seen during the procedures compared to the baseline before the procedure. Previously, pulse wave analysis was successfully shown to distinguish between the signals ipsilateral and contralateral to the occlusion in stroke patients [1], and pulse wave velocity was used to determine a correlation in acute stroke patients between cerebral arterial stiffness and intracranial artery calcification [2].
The procedures in this study include carotid artery stenting, aneurysms, and thrombectomies. Thrombectomies, although the minority of cases (n=3), are particularly informative as they are performed on patients who developed LVOs and therefore allow a comparison of the recorded pulse waves during a naturally occurring LVO versus during the period following the procedure after the occlusion has been cleared.
Methods
At the time of analysis, three subjects were recorded while undergoing a thrombectomy. Here we present the results from a representative subject who underwent a thrombectomy. The subject (GMC027) is a 77-year-old male with an LVO in his right middle cerebral artery.
Pulse wave velocity (PWV) was calculated using the distance between sensors (15 cm) divided by the difference in time between the pulse wave foot recording in two adjacent sensors (channels 0 and 1) placed on the carotid artery ipsilateral to the occlusion. Analysis along with calculation of statistics was performed in Matlab (R2023a).
Results
Figure 1 shows the average PWV with the x-axis going forward in time from left to right with measurements before the procedure, during the procedure, both during and between the inflation of balloons, and post-procedure. The successful treatment of the stroke by the performance of a thrombectomy is accompanied by a clear decrease in the PWV, as can be seen by comparing the values before and after the procedure (2.33 ± 0.18 m/s and 1.76 ± 0.65 m/s respectively, t score = 10.6 p<0.0001).
This result is proof of concept that hemodynamic changes, as recorded by sensors over the carotid artery, can be used to detect differences caused by the presence of a stroke-inducing LVO.
The procedures in this study include carotid artery stenting, aneurysms, and thrombectomies. Thrombectomies, although the minority of cases (n=3), are particularly informative as they are performed on patients who developed LVOs and therefore allow a comparison of the recorded pulse waves during a naturally occurring LVO versus during the period following the procedure after the occlusion has been cleared.
Methods
At the time of analysis, three subjects were recorded while undergoing a thrombectomy. Here we present the results from a representative subject who underwent a thrombectomy. The subject (GMC027) is a 77-year-old male with an LVO in his right middle cerebral artery.
Pulse wave velocity (PWV) was calculated using the distance between sensors (15 cm) divided by the difference in time between the pulse wave foot recording in two adjacent sensors (channels 0 and 1) placed on the carotid artery ipsilateral to the occlusion. Analysis along with calculation of statistics was performed in Matlab (R2023a).
Results
Figure 1 shows the average PWV with the x-axis going forward in time from left to right with measurements before the procedure, during the procedure, both during and between the inflation of balloons, and post-procedure. The successful treatment of the stroke by the performance of a thrombectomy is accompanied by a clear decrease in the PWV, as can be seen by comparing the values before and after the procedure (2.33 ± 0.18 m/s and 1.76 ± 0.65 m/s respectively, t score = 10.6 p<0.0001).
This result is proof of concept that hemodynamic changes, as recorded by sensors over the carotid artery, can be used to detect differences caused by the presence of a stroke-inducing LVO.