VERiTAS II REFRESHED

• ClinicalTrials.gov Identifier: NCT03729817
• Recruitment Status: Not yet recruiting
• First Posted: November 5, 2018
• Last Update Posted: October 19, 2020
• Sponsor: University of Illinois at Chicago
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Sepideh Amin-Hanjani, University of Illinois at Chicago

Tracking Information

• First Submitted Date: October 16, 2018
• First Posted Date: November 5, 2018
• Last Update Posted Date: October 19, 2020
• Estimated Study Start Date: February 1, 2022
• Estimated Primary Completion Date: January 31, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 13, 2020)

Device Safety - based on periprocedural risk of any stroke and death [ Time Frame: 30 days ]

Any stroke (ischemic or hemorrhagic), or death, within 30 days following submaximal angioplasty

Original Primary Outcome Measures (submitted: October 31, 2018)

Periprocedural stroke and death [ Time Frame: post-procedure within 30 days ]

Any stroke (ischemic or hemorrhagic) or death (from any cause) in the periprocedural (30 day) period as an indication of device safety

Current Secondary Outcome Measures (submitted: October 13, 2020)

• Clinical Efficacy - based on periprocedural stroke/death and subsequent in-territory stroke [ Time Frame: 1 year ]
  Any stroke/death within 30 days or ischemic stroke in the symptomatic vessel territory at one year
• Hemodynamic Success - based on improvement of blood flow on QMRA in the treated vessel [ Time Frame: post procedure (within 7 days) ]
  Initial hemodynamic effect of submaximal balloon angioplasty in the treated vessel measured by ml/min on QMRA
• Hemodynamic Durability - based on sustained improvement of blood flow on QMRA in the treated vessel or vascular territory [ Time Frame: 1 year ]
  Hemodynamic durability of submaximal balloon angioplasty at follow-up in the treated vessel or vascular territory measured by ml/min on QMRA

Original Secondary Outcome Measures (submitted: October 31, 2018)

• Hemodynamic effect of submaximal angioplasty [ Time Frame: post-procedure within 7 days ]
  Initial hemodynamic success of the procedure indicated by improvement of flow status from low to normal
• Hemodynamics durability of submaximal angioplasty [ Time Frame: 12 and 24 months post-procedure ]
  Sustained hemodynamic success of the procedure
• Subsequent posterior circulation stroke [ Time Frame: 12 months post-procedure ]
  Estimate the risk of subsequent posterior circulation stroke (at one year) following submaximal balloon angioplasty for distal flow compromised symptomatic intracranial vertebrobasilar stenosis (preliminary clinical efficacy).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: VERiTAS II REFRESHED
• Official Title: Vertebrobasilar Stroke and Risk of Transient Ischemic Attack and Stroke (VERiTAS) II - Restoring Flow by Revascularization With Submaximal Angioplasty in Hemodynamic Intracranial Atherosclerotic Disease (REFRESHED) Study
• Brief Summary: Recent prospective observational data has established that hemodynamic compromise identifies a high risk subgroup of patients with symptomatic intracranial atherosclerotic disease. The currently proposed study aims to determine if an endovascular intervention, submaximal balloon angioplasty, can be performed with adequate safety in this high risk subgroup of hemodynamically-compromised patients with intracranial atherosclerotic stenosis. The study will also examine as secondary aims, the effect of the intervention on hemodynamics and on subsequent in-territory ischemic events.

Detailed Description

VERiTAS II REFRESHED is a prospective single-arm multi-center study to assess the safety of submaximal balloon angioplasty in conjunction with intensive medical management in patients with hemodynamically-compromised symptomatic 70-99% atherosclerotic intracranial stenosis (ICAS). This study builds on lines of evidence from prior prospective studies which established the markedly elevated risk of subsequent stroke in patients with hemodynamic compromise, and preliminary data from small case series which support submaximal angioplasty as a potentially safe option for revascularization. The primary objective of the current study is to determine the safety of submaximal balloon angioplasty for treatment of hemodynamically-compromised symptomatic ICAS. The secondary objectives are to obtain preliminary estimates of the risk of subsequent in-territory stroke at one year, to evaluate the hemodynamic effect of submaximal balloon angioplasty on distal blood flow, and to examine the hemodynamic durability of submaximal balloon angioplasty over follow-up.

A total of 124 patients will be enrolled in this open-label study to receive the submaximal angioplasty intervention in conjunction with intensive medical management. Patients with stroke attributable to ICAS serve as the source population for the study, and will be identified as inpatients or outpatients at participating centers or their referring site. Patients with recently (within 30 days prior to enrollment) symptomatic 70-99% ICAS of the intracranial internal carotid (ICA), middle cerebral (MCA), vertebral (VA) or basilar (BA) artery will first be identified by a standard of care screening imaging modality (CTA, MRA, DSA). If the patient is eligible based on available inclusion/exclusion criteria, informed consent will be obtained and MRI/ quantitative magnetic resonance angiography (QMRA) will be performed (if not already as standard care); patients demonstrating evidence of hemodynamic compromise based on borderzone infarct pattern for the anterior circulation (ICA and MCA) and by low flow state on QMRA for the posterior circulation (VA and BA) will be enrolled. QMRA will be used for determination of eligibility in posterior circulation ICAS patients, but will be performed in both anterior and posterior circulation patients as a baseline for hemodynamic comparison post-procedure. The patient will then undergo catheter angiography (if not performed already as standard care) to confirm eligible intracranial ICAS.

The participant will undergo submaximal angioplasty in accordance with the study protocol within 48 hours of angiographic confirmation, followed by SAMMPRIS regimen intensive medical management, including initial dual antiplatelet therapy (aspirin and Clopidogrel for 3 months followed by aspirin monotherapy), and targeting primary and secondary stroke risk factors. Assistance in achieving the risk factor goals will be provided by an INTERxVENT lifestyle coach, who will call the participant by phone at 1, 3, 5, 7, 9, 11 weeks, and then every 4 weeks throughout follow-up. On a scheduled basis, INTERxVENT will send a report of the participants progress and goals for risk factor modification, to the participant and study coordinator/ study neurologist. Participants will have follow-up for a total of one year. All participants will have clinical visits at 1, 4, 8, and 12 months, performed by local study personnel not directly involved with the intervention. The study visits will include assessment of neurological, functional and cognitive status, as well as status of primary and secondary stroke risk factor control. QMRA will be performed post procedure and at 12 months; the follow-up QMRA results will be blinded to the local study personnel and patients. The main outcomes of interest are: (1) any periprocedural (within 30 day) stroke or death; (2) stroke in the symptomatic vessel territory; and (3) distal flow status post procedure and at follow-up (using QMRA). Additional measured endpoints will included functional and cognitive outcomes at follow-up.

The sample size calculations have been based on a confidence interval (CI) approach aimed determining if the intervention can be performed with a clinically specified periprocedural event rate of 5% (90% CI 2,10%), in order to establish sufficient periprocedural safety of submaximal angioplasty to warrant further investigation in a future randomized trial. The sample size calculation assumes a CI approach around the stroke/death event rate at 30 days; for the presumed event rate of 5%, a sample size of N=117 would yield a 90% CI of (2%,10%). Adjusting for the inflation factor 1.02 due to a planned interim analysis and a 4% attrition rate for the 30 day follow-up, 124 patients are required for analysis of the primary safety endpoint. An interim analysis of safety is planned with a stopping rule if 30 day periprocedural risk exceeds 5 % (i.e. lower bound of CI of observed estimate exceeds the threshold). To ensure that the intervention is stopped early if it is harmful, the timing of the interim analysis will be flexible, to occur once 30 day follow-up has been completed on one third of patients (41 patients) or alternatively, when 12 events are observed, whichever comes first; the number of events, 12, has been specified as the minimal event number which would result in the lower bound of the 90% CI exceeding 5% and thus claim a >5% event rate. As related to study's go/no go criteria for a future phase 3 trial, our definitive no go parameter is proposed as the lower bound of the observed pre-specified CI exceeding the safety (30 day periprocedural risk) threshold of 5%. Other outcomes from the study (i.e. the secondary clinical and hemodynamic endpoints at 12m) would also be taken into account in determining whether the procedure warrants additional study in a phase 3 trial.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

subjects will be recruited into a single arm undergoing intervention.

Masking: None (Open Label)
Primary Purpose: Other

Condition

• Intracranial Atherosclerotic Disease
• Stroke

Intervention

Device: Submaximal balloon angioplasty

An endovascular procedure involving inflation of a balloon catheter undersized to 50-70% of normal vessel diameter to perform angioplasty of a stenotic blood vessel segment, with the goal of increasing blood flow.

Study Arms

Experimental: Submaximal balloon angioplasty

Endovascular intervention with submaximal balloon angioplasty

Intervention: Device: Submaximal balloon angioplasty

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: October 4, 2020): 124
• Original Estimated Enrollment (submitted: October 31, 2018): 62
• Estimated Study Completion Date: January 2028
• Estimated Primary Completion Date: January 31, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Participants must meet all inclusion criteria for enrollment into the study

• Non-severe recent stroke (within 30 days) attributed to 70-99% stenosis of intracranial artery (ICA, MCA, VA, BA) - may be diagnosed by MRA, CTA or DSA to qualify for angiogram performed as part of the study, but must be confirmed by catheter angiography for enrollment into the trial
• Hemodynamic compromise based on borderzone infarct pattern for the anterior circulation (ICA and MCA) and by low flow state on QMRA for the posterior circulation (VA and BA).
• Target vessel with minimal nominal diameter of 2mm
• Target length of stenosis <18mm
• Symptoms within 30 days of enrollment
• Age 18 and above
• Able to provide informed consent

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from study participation

Neurologic:

• Major disabling stroke mRS >3; progressive or fluctuating deficit within 24 hours
• Hemorrhagic infarction (based on CT) within 14 days of enrollment
• Any large stroke (>5cm) to be at risk for hemorrhagic conversion

Medical:

• Any neurological disease which would confound follow-up assessment
• Any co-morbid disease condition with <12 month life expectancy
• Known cardiac disease associated with elevated cardioembolic risk, specifically, atrial fibrillation, prosthetic valve, endocarditis, left atrial/ventricular thrombus, cardiomyopathy with EF<25%, cardiac myxoma
• Blood dyscrasias, specifically polycythemia vera, essential thrombocytosis, sickle cell disease
• Active bleeding diathesis, h/o major systemic hemorrhage within 30 days, active PUD, platelets<100K (severe liver impairment (AST or ALT>3 x normal, cirrhosis)

Target lesion:

• Non-atherosclerotic stenosis including dissection, fibromuscular dysplasia, vasculitis, radiation induced vasculopathy, suspected recanalized embolus, suspected vasospastic process
• Mori C classification of stenosis(i.e. diffuse lesion, extremely angulated >90⁰, excessive proximal tortuosity)Previous treatment of target lesion with stent, angioplasty or other mechanical device
• Extracranial vertebral artery or carotid artery tortuosity, stenosis or occlusion prohibiting access to the target lesion (Extracranial disease is not exclusionary if does not prohibit access to target lesion)

Participant:

• Unable or unwilling to undergo MRI
• Unable to undergo cerebral angiography
• Pregnancy
• Concurrent participation in another study which would conflict with the current study
• Allergy or contraindication to aspirin or Plavix
• Indication for warfarin or NOAC beyond enrollment (e.g. venous thrombo-embolism, atrial fibrillation)
• Thrombolytic therapy within 24 hours

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sepideh Amin-Hanjani, MD; 312-355-2050; hanjani@uic.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03729817
• Other Study ID Numbers: 2020
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Sepideh Amin-Hanjani, University of Illinois at Chicago
• Study Sponsor: University of Illinois at Chicago
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Sepideh Amin-Hanjani, MD; University of Illinois at Chicago
• Principal Investigator: Adnan Siddiqui, MD; University at Buffalo
• Principal Investigator: Tanya Turan, MD; Medical University of South Carolina

• PRS Account: University of Illinois at Chicago
• Verification Date: October 2020