Appraising the Embolization of Aneurysms Using Balt Optima™ Coil System (APPLY Study)

Study Overview
=================
Brief Summary
-----------------
In recent years, many developments have been made to the tools and techniques used to treat IAs via endovascular intervention. Specifically, to the detachable coils themselves. In March 2018, the US Food and Drug administration granted Balt USA 510(k) clearance for the Optima Coil System™. Earlier this year, the list of devices included within the system has expanded to include OptiMAX Complex Super Soft and Complex Soft coils. It consists of coils that come in Standard, Soft and Super Soft profiles and allows for instant detachment from the pusher. The APPLY study is a prospective, single-center investigator-initiated study meant to assess the use of the Balt Optima™ Coil System. The site is looking to enroll approximately 30 subjects over the course of two years. The Optima Coil System™ is commercially available in the United States as such this study is looking for real-world data.

Detailed Description
-----------------
Intracranial aneurysms both ruptured and unruptured collectively affect a significant portion of the general population. Cases of unruptured intracranial aneurysms (UIA) are estimated to affect roughly 3% of the general population and aneurysmal subarachnoid hemorrhage (aSAH) has an incidence of 8 to 9 people per 100,000. There are two well-established treatment options for patients diagnosed with intracranial aneurysms (IA): surgical clipping and endovascular coiling. Neurosurgical intervention requires a craniotomy followed by the clipping of the aneurysm. Endovascular repair is minimally invasive as access to the afflicted vessel is gained through the femoral artery with the assistance of imaging guidance. During embolization, the aneurysm is occluded using coils of varying length, diameter, and softness. By filling the dome of the aneurysm physicians aim to prevent further blood flow into the bulge which will prevent the aneurysm from rupturing. In addition to coiling a stent may be placed to function as a blood flow diverting device. The first-ever recorded use of coils in the treatment of intracranial aneurysms by way of endovascular intervention was in 1988. In 1989, detachable coils were designed by Guido Guglielmi, an endovascular neurosurgeon, who pioneered the concept of coil embolization. Since then, endovascular embolization has become effective, and in some cases preferred, method of treatment of intracranial aneurysms. A 2005 randomized, multicenter study titled International Subarachnoid Aneurysm Trial (ISAT) demonstrated that in comparison to surgical clipping, endovascular repair clinical outcomes result in significant risk reduction and long-term independence post-procedure. To verify their findings the ISAT authors reviewed the clinical outcomes at 1 year of 1063 of 1072 patients who underwent ruptured aneurysm embolization using detachable coils compared to 1055 of 1070 who were designated to neurosurgical clipping. At the one-year mark patients who experienced endovascular repair demonstrated poor prognosis with less frequency, as measured by mortality and extent of dependency, in 23.5% of cases in comparison to 30.9% of subjects treated via neurosurgical intervention. While the results seem to show a considerable preference for embolization, the patients in this designated sample were found to experience rebleeds at a higher frequency. Beyond resurgence of hemorrhaging, embolization risks include aneurysm perforation and/or rupture, thromboembolic events, and coil herniation out of the occluded site. Despite the aforementioned risk factors, it has become clear that embolization with detachable coils is a much safer treatment option as the rate of procedure-related complications is relatively low. This is true for patients with unruptured and ruptured intracranial aneurysms-size and location did not show any statistically significant impact. The study will enroll approximately 30 subjects to allow us to adequately observe the benefits of the central limit theorem. Based on prior experience, we expect that approximately 10% of all participants may be lost to follow-up and/or will withdraw from the study. It is estimated that two years are needed to complete the study. The first year will be necessary to enroll 30 subjects and the second year will be necessary to complete the 12-month follow-up visits and study close out procedures. The device is to be used per Instructions for Use as indicated for treatment of intracranial aneurysms by way of coil embolization. Participating in this study will not contribute or be of detriment in any way of a subject's medical care. All study related data gathering activities are standard of care and do not require any special actions.

Official Title
-----------------
APPLY Study: A Prospective, Single Center Study Appraising the Embolization of Aneurysms Using the Balt Optima™ Coil System

Conditions
-----------------
Aneurysm, Intracranial Aneurysm, Ruptured Aneurysm, Subarachnoid Hemorrhage, Aneurysmal, Cerebral Aneurysm Unruptured

Intervention / Treatment
-----------------
* Device: Optima Coil System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients age ≥ 18 Patients undergoing the embolization of large or small intracranial aneurysms Patient's physician has decided that the best treatment for the patient's neurovascular abnormalities is the Optima Coil System and the patient has agreed to the treatment Of the total number of coils implanted Optima™ Coil System accounts for at least 80% Fully executed IRB approved Informed Consent Exclusion Criteria: Patient participation in another study that may disrupt the results of this study Anticipated life expectancy of less than 12-months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a prospective, single-arm, single-center, post-market, real-world, investigator-initiated study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with Optima Balt Coils<br>The APPLY study is a single-arm prospective study which means that everyone enrolled in the clinical trial will be/has been treated with the Optima Balt Coils. | Device: Optima Coil System<br>* Patients who have qualified for endovascular coiling in effort to treat intracranial aneurysms were treated with<br>* Other names: Neurovascular Embolization Device;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occlusion Rates | Successful occlusion rates defined as Raymond-Roy Occlusion Class I and II. | 12 Months | 
| Mortality | All-cause mortality. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occlusion Scale Score | Raymond-Roy Occlusion classification is measured via angiographic imaging of endovascularly treated intracranial aneurysms. The classes are the following: Class I indicates complete obliteration of the aneurysm. Class II indicates that post-coiling some residual neck is left. Class IIIa indicates residual aneurysm remains after coiling but these are likely to improve to Class I or II over time. Class IIIb indicates residual aneurysm remains but these are wider and larger, they also have a higher retreatment rate. Ideal aneurysm coiling classification post procedure is Class I, Class II, and in some cases Class IIIa. | Immediately post-procedure, 3-Months, and 12-Months | 
| Modified Rankin Scale (mRS) | Good Clinical Outcome defined as mRS = 0 - 2. The modified Rankin Scale measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other neurological disability via interview of subject or family. The scale ranges from 0 to 6, with 0 being the best outcome and 6 being the worst. Score 0 = patient shows no symptoms. Score 1 = no significant disability despite some symptoms, but patient is able to carry out all usual duties/activities. Score 2 = slight disability, patient is unable to carry out all previous activities but is able to look after their own affairs. Score 3 = moderate disability, requiring some help, but able to walk without assistance. Score 4 = moderate severe disability, patient is unable to walk and/or attend to their own bodily needs. Score 5 = severe disability, patient is bedridden, incontinent and requires constant nursing care. Score 6 = patient has expired. | Up to 1 year during various scheduled visits. Specifically, at discharge from hospital, at 3-month follow up and again at 12-months. | 
| Packing Density | Number of coils necessary for packing density | Result is known immediately post-procedure. | 
| Fluro Time | Fluro time per case. | Result is known immediately post-procedure. | 
| Other Devices Used | Use of adjuncts, stent/balloon/Comaneci | Result is known immediately post-procedure. | 
| Complications | Major complications (i.e. intraoperative complications: inadvertent coil detachment, rupture/re-rupture, retreatment) | At all time points from procedure to 12 Months. | 
| SAE | Serious Adverse Events post-procedure at discharge, 3-months, and through the final 12-month visit-device related or otherwise. | At all time points from procedure to 12 Months. | 
| Thromboembolic Events | Post-treatment major thromboembolic events are defined as stroke events that occur immediately after the index procedure. Post endovascular coiling subjects are often at risk for stroke, this occurs as a formation in the blood vessel of a clot breaks loose and is carried by the blood stream and occludes another vessel. Thromboembolic events represent one of the most serious complications of embolization therapy, due to the possibility of permanent neurologic disability and death. As such these events will be closely monitored. This is not a quantitative or qualitative measurement but rather an archive of the circumstances should an event occur. | At all time points from procedure to 12 Months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Brain aneurysm, Optima Coil System, Endovascular Coiling, Embolization, Ruptured Intracranial Aneurysm, Unruptured Intracranial Aneurysm