The Capillary Index Score Trial

• Sponsor: Firas Al-Ali (Other)
• Overall Status: Completed
• CT.gov ID: NCT02618031
• Collaborator: Stryker Neurovascular (Industry), Rochester General Hospital (Other), University of Vermont Medical Center (Other), University of North Carolina, Chapel Hill (Other), NYU Langone Health (Other), WellStar Health System (Other)
• Enrollment: 57
• Locations: 6
• Arms: 2
• Actual Duration (Months): 34
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study seeks to investigate the capillary index score (CIS) to further improve patient selection of endovascular treatment (EVT) in acute ischemic stroke (AIS).

The hypothesis or idea being tested:

Patients with favorable CIS who are successfully revascularized with EVT can have successful outcomes with an extended time window for treatment.

Condition or Disease	Intervention/Treatment	Phase
Acute Stroke; Brain Ischemia; Ischemic Stroke	Procedure: Endovascular Treatment (EVT)	Phase 1

Detailed Description

This study is trying to look at how the well-being of the patient following treatment is influenced by peripheral blood supply (collateral flow) to the area lacking primary blood flow due to the clot. Treatment of AIS includes EVT and medical treatment. EVT is typically not offered to patients after 6 hours of the onset of symptoms. The current study is based on the belief that patients can be successfully treated with the EVT up to 8 hours, as long as they have good peripheral blood flow (collateral flow) to the area of tissue blocked of the primary blood supply.

The study will evaluate the ability of the capillar index score (CIS) to identify patients who can be successfully treated with EVT. The CIS quantifies blood supply to the ischemic area from peripheral vessels (collateral flow) based on diagnostic cerebral angiogram. Patients are graded on a scale from 0-3, with 0 and 1 considered a poor CIS (pCIS) and 2 and 3 considered a favorable CIS (fCIS). All patients will be treated with EVT and medical treatment consistent with national guidelines.

The primary endpoint is the clinical outcome at 90 days between fCIS group versus pCIS group. The secondary endpoint is the influence of successful revascularization on outcomes for patients with fCIS or pCIS.

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be assigned to one of two groups based on the outcome of diagnostic evaluation. Treatment will be identical for the two groups.Patients will be assigned to one of two groups based on the outcome of diagnostic evaluation. Treatment will be identical for the two groups.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: The participants and investigators evaluating 90 day outcomes will be blinded to the group.
• Primary Purpose: Diagnostic
• Official Title: The Capillary Index Score Trial: Phase I
• Actual Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Aug 31, 2018
• Actual Study Completion Date: Dec 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Favorable CIS Patients with a favorable CIS (fCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines.	Procedure: Endovascular Treatment (EVT); EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tPA (tissue plasminogen activator) directly at the site of the clot. The protocol calls for use of the Trevo stent retriever (Stryker Neurovascular) for the first pass of clot removal.; Other Names: Intra-arterial Treatment (IAT)
Experimental: Poor CIS Patients with a poor CIS (pCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines.	Procedure: Endovascular Treatment (EVT); EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tPA (tissue plasminogen activator) directly at the site of the clot. The protocol calls for use of the Trevo stent retriever (Stryker Neurovascular) for the first pass of clot removal.; Other Names: Intra-arterial Treatment (IAT)

Outcome Measures

Primary Outcome Measures

1. Modified Rankin Score (mRS) Between Favorable CIS Group Versus Poor CIS Group. [90 days]

   The mRS Score ranges from 0-6 and describes the degree of disability or dependence after a stroke. The grades are no symptoms (0), no significant disability (1), slight disability (2), moderate disability (3), moderately severe disability (4), severe disability (5), and death (6).

Secondary Outcome Measures

1. Complication Rate Between Favorable CIS Group Versus Poor CIS Group [1 day - 1 week]

   Complication : Clinically relevant intracranial hemorrhage and vasogenic edema as defined by parenchymal hematoma (PH) 1 or 2

2. Modified Rankin Score (mRS) Between Favorable CIS With Good Revascularization Versus Poor CIS With Good Revascularization. [90 days]

   Revascularization status will be classified as poor (mTICI = 0-2A) or good (mTICI = 2B, 3). Rate of good clinical outcomes between groups will be compared based on the combination of CIS and revascularization status. Good outcome will be measured based on the modified Rankin scale score according to: 0: No symptoms No significant disability despite symptoms Slight disability Moderate disability Moderately severe disability Severe disability Dead A score of 0-2 is considered a good outcome

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Anterior circulation acute ischemic stroke due to blockage of the intracranial internal carotid artery or middle cerebral artery (M1)

2. Within 24 hours of onset of symptoms

3. NIHSS Score is 8 or greater

Exclusion Criteria:

1. Contra-indication for IAT found on initial CT

2. Intracranial hemorrhage

3. Stroke mimics (tumor, herpetic encephalitis, etc.)

4. More than 1/3 hypodensity on non-enhanced head CT prior to intervention

5. ASPECT Score less than 6

6. Pre-existing disability defined as modified Rankin Scale (mRS) score more than 2

7. Pregnant women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	WellStar Atlanta Medical System	Atlanta	Georgia	United States	30312
2	New York University Langone Medical Center	New York	New York	United States	10016
3	Rochester General Hospital	Rochester	New York	United States	14621
4	University of North Carolina Hospital	Chapel Hill	North Carolina	United States	27514
5	Akron General Medical Center	Akron	Ohio	United States	44307
6	University of Vermont Medical Center	Burlington	Vermont	United States	05401

Sponsors and Collaborators

• Firas Al-Ali
• Stryker Neurovascular
• Rochester General Hospital
• University of Vermont Medical Center
• University of North Carolina, Chapel Hill
• NYU Langone Health
• WellStar Health System

Investigators

• Principal Investigator: Firas Al-Ali, MD, Akron General Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 30, 2018

More Information

Publications

• Al-Ali F, Elias JJ, Filipkowski DE, Faber JE. Acute ischemic stroke treatment, part 1: patient selection "the 50% barrier and the capillary index score". Front Neurol. 2015 Apr 22;6:83. doi: 10.3389/fneur.2015.00083. eCollection 2015. Review.
• Al-Ali F, Elias JJ, Filipkowski DE. Acute Ischemic Stroke Treatment, Part 2: Treatment "Roles of Capillary Index Score, Revascularization and Time". Front Neurol. 2015 Jun 1;6:117. doi: 10.3389/fneur.2015.00117. eCollection 2015. Review.
• Al-Ali F, Elias JJ, Tomsick TA, Liebeskind DS, Broderick JP; IMS Study Groups. Relative Influence of Capillary Index Score, Revascularization, and Time on Stroke Outcomes From the Interventional Management of Stroke III Trial. Stroke. 2015 Jun;46(6):1590-4. doi: 10.1161/STROKEAHA.115.009066. Epub 2015 May 7.
• Al-Ali F, Jefferson A, Barrow T, Cree T, Louis S, Luke K, Major K, Nemeth D, Smoker S, Walker S. The capillary index score: rethinking the acute ischemic stroke treatment algorithm. Results from the Borgess Medical Center Acute Ischemic Stroke Registry. J Neurointerv Surg. 2013 Mar;5(2):139-43. doi: 10.1136/neurintsurg-2011-010146. Epub 2012 Jan 19.
• Al-Ali F, Tomsick TA, Connors JJ 3rd, Gebel JM, Elias JJ, Markarian GZ, Al-Ali Z, Broderick JP. Capillary Index Score in the Interventional Management of Stroke trials I and II. Stroke. 2014 Jul;45(7):1999-2003. doi: 10.1161/STROKEAHA.114.005304. Epub 2014 May 22.

• Responsible Party: Firas Al-Ali, Neurointerventionalist, Akron General Medical Center
• ClinicalTrials.gov Identifier: NCT02618031
• Other Study ID Numbers: CIS Trial
• First Posted: Dec 1, 2015
• Last Update Posted: Feb 5, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Firas Al-Ali, Neurointerventionalist, Akron General Medical Center: capillary index score; acute ischemic stroke; collateral circulation; cerebral ischemia; diagnostic imaging
• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Brain Ischemia; Ischemia

Study Results

Participant Flow

Pre-assignment Detail	Final assignment to a group was not determined until the diagnostic cerebral angiograms were evaluated by the core lab at the end of the study to quantify the Capillary Index Score for each subject. Preliminary assessment of group was determined by the operators at the time of treatment.

Arm/Group Title	Favorable CIS	Poor CIS
Arm/Group Description	Patients with a favorable CIS (fCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines. Endovascular Treatment (EVT): EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tPA directly at the site of the clot.	Patients with a poor CIS (pCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines. Endovascular Treatment (EVT): EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tPA directly at the site of the clot.
Period Title: Overall Study
STARTED	46	11
COMPLETED	45	11
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Favorable CIS	Poor CIS	Total
Arm/Group Description	Patients with a favorable Capillary Index Score (fCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines. Endovascular Treatment (EVT): EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tissue plasminogen activator (tPA) directly at the site of the clot.	Patients with a poor Capillary Index Score (pCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines. Endovascular Treatment (EVT): EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tissue plasminogen activator (tPA) directly at the site of the clot.	Total of all reporting groups
Overall Participants	46	11	57
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	70	73	70
Sex: Female, Male (Count of Participants)
Female	33 71.7%	7 63.6%	40 70.2%
Male	13 28.3%	4 36.4%	17 29.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	46 100%	11 100%	57 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.2%	0 0%	1 1.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 8.7%	2 18.2%	6 10.5%
White	41 89.1%	9 81.8%	50 87.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	46 100%	11 100%	57 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	165 (14)	171 (6)	166 (13)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	82 (25)	95 (20)	85 (24)
diabetes (Count of Participants)
Count of Participants [Participants]	7 15.2%	3 27.3%	10 17.5%
blood pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	147 (32)	156 (32)	149 (32)
occlusion site (Count of Participants)
middle cerebral artery (MCA)	31 67.4%	4 36.4%	35 61.4%
internal carotid artery (ICA)	2 4.3%	1 9.1%	3 5.3%
combination	13 28.3%	6 54.5%	19 33.3%
ischemic site (Count of Participants)
MCA	41 89.1%	6 54.5%	47 82.5%
ICA	1 2.2%	1 9.1%	2 3.5%
combination	4 8.7%	4 36.4%	8 14%
National Institutes of Health stroke scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	17 (5)	21 (7)	18 (6)

Outcome Measures

1. Primary Outcome

Title	Modified Rankin Score (mRS) Between Favorable CIS Group Versus Poor CIS Group.
Description	The mRS Score ranges from 0-6 and describes the degree of disability or dependence after a stroke. The grades are no symptoms (0), no significant disability (1), slight disability (2), moderate disability (3), moderately severe disability (4), severe disability (5), and death (6).
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

A good outcome is defined as mRS 0-2

Arm/Group Title	Favorable CIS	Poor CIS
Arm/Group Description	Patients with a favorable CIS (fCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines. Endovascular Treatment (EVT): EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tPA directly at the site of the clot.	Patients with a poor CIS (pCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines. Endovascular Treatment (EVT): EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tPA directly at the site of the clot.
Measure Participants	45	11
mRS 0-2	22 47.8%	1 9.1%
mRS 3-6	23 50%	10 90.9%

2. Secondary Outcome

Title	Complication Rate Between Favorable CIS Group Versus Poor CIS Group
Description	Complication : Clinically relevant intracranial hemorrhage and vasogenic edema as defined by parenchymal hematoma (PH) 1 or 2
Time Frame	1 day - 1 week

Outcome Measure Data

Analysis Population Description

post-operative bleeding was not available for two subjects who died before a postoperative scan

Arm/Group Title	Favorable CIS	Poor CIS
Arm/Group Description	Patients with a favorable CIS (fCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines. Endovascular Treatment (EVT): EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tPA directly at the site of the clot.	Patients with a poor CIS (pCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines. Endovascular Treatment (EVT): EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tPA directly at the site of the clot.
Measure Participants	45	10
PH 1 or 2	1 2.2%	4 36.4%
no PH1 or 2	44 95.7%	6 54.5%

3. Secondary Outcome

Title	Modified Rankin Score (mRS) Between Favorable CIS With Good Revascularization Versus Poor CIS With Good Revascularization.
Description	Revascularization status will be classified as poor (mTICI = 0-2A) or good (mTICI = 2B, 3). Rate of good clinical outcomes between groups will be compared based on the combination of CIS and revascularization status. Good outcome will be measured based on the modified Rankin scale score according to: 0: No symptoms No significant disability despite symptoms Slight disability Moderate disability Moderately severe disability Severe disability Dead A score of 0-2 is considered a good outcome
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

output = number of patients with a good outcome one patient was lost to follow up

Arm/Group Title	Favorable CIS and Good Revascularization	Poor CIS and Good Revascularization	Favorable CIS and Poor Revascularization	Poor CIS and Poor Revascularization
Arm/Group Description	Patients with a favorable CIS (fCIS) who achieve good revascularization based on modified treatment in cerebral infarction (mTICI) score of 2B or 3 Following endovascular treatment (EVT), revascularization was graded based on the mTICI classification according to: grade 0: no perfusion grade 1: antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion grade 2A: antegrade reperfusion of less than half of the occluded target artery previously ischemic territory grade 2B: antegrade reperfusion of more than half of the previously occluded target artery ischemic territory grade 3: complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches	Patients with a poor CIS (pCIS) who achieve good revascularization based on modified treatment in cerebral infarction (mTICI) score of 2B or 3 Following endovascular treatment (EVT), revascularization was graded based on the mTICI classification according to: grade 0: no perfusion grade 1: antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion grade 2A: antegrade reperfusion of less than half of the occluded target artery previously ischemic territory grade 2B: antegrade reperfusion of more than half of the previously occluded target artery ischemic territory grade 3: complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches	Patients with a favorable CIS (fCIS) who achieve poor revascularization based on modified treatment in cerebral infarction (mTICI) score of 0, 1, or 2A Following endovascular treatment (EVT), revascularization was graded based on the mTICI classification according to: grade 0: no perfusion grade 1: antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion grade 2A: antegrade reperfusion of less than half of the occluded target artery previously ischemic territory grade 2B: antegrade reperfusion of more than half of the previously occluded target artery ischemic territory grade 3: complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches	Patients with a poor CIS (pCIS) who achieve poor revascularization based on modified treatment in cerebral infarction (mTICI) score of 0, 1, or 2A Following endovascular treatment (EVT), revascularization was graded based on the mTICI classification according to: grade 0: no perfusion grade 1: antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion grade 2A: antegrade reperfusion of less than half of the occluded target artery previously ischemic territory grade 2B: antegrade reperfusion of more than half of the previously occluded target artery ischemic territory grade 3: complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches
Measure Participants	36	8	9	3
Good outcome	19 41.3%	1 9.1%	3 5.3%	0 NaN
Poor outcome	17 37%	7 63.6%	6 10.5%	3 NaN

Adverse Events

Time Frame	3 months
Adverse Event Reporting Description	All subjects in the study are considered at risk for death due to the nature of the stroke.
Arm/Group Title	Favorable CIS		Poor CIS
Arm/Group Description	Patients with a favorable CIS (fCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines. Endovascular Treatment (EVT): EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tPA directly at the site of the clot.		Patients with a poor CIS (pCIS) will receive endovascular treatment (EVT) and medical treatment consistent with national guidelines. Endovascular Treatment (EVT): EVT is an endovascular procedure in which a catheter is inserted into an artery and directed to the site of the blocked blood vessel in the brain. The clot is removed using a mechanical device with or without an injection of tPA directly at the site of the clot.
All Cause Mortality
	Favorable CIS		Poor CIS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/45 (17.8%)		7/11 (63.6%)
Serious Adverse Events
	Favorable CIS		Poor CIS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/45 (2.2%)		0/11 (0%)
Vascular disorders
hemorrhage	1/45 (2.2%)	1	0/11 (0%)	1
Other (Not Including Serious) Adverse Events
	Favorable CIS		Poor CIS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/45 (4.4%)		1/11 (9.1%)
General disorders
radiation	2/45 (4.4%)	2	1/11 (9.1%)	1

Limitations/Caveats

The sample size was limited by funding available to support the trial. The assignment of Capillary Index Score (CIS) by an independent core lab at the end of the trial led to a lower number of subjects in the poor CIS group than planned.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.