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IVIG in Acute Ischemic Stroke: A Pilot Study (IVIG/AIS)

Primary Purpose

Ischemic Stroke

Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Privigen
Normal Saline
Sponsored by
Inova Health Care Services
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring IVIg, Acute Ischemic Stroke, Stroke, CVA, Cerebrovascular Accident

Eligibility Criteria

45 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Onset of neurological symptoms between 4.5 and 8 hours
  2. Male or Female age 45 -75 years old
  3. Score of 10-15 points on the National Institutes of Health Stroke Scale (NIHSS) with clinical signs suggestive of ischemic stroke
  4. Acute brain ischemia with a distinct penumbra (at least 20%), measured by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI), in the territory of the middle cerebral artery, anterior cerebral artery, or posterior cerebral artery with a hemispheric distribution
  5. Ability and willingness to provide informed consent and comply with study requirements and procedures

Exclusion Criteria:

  1. Eligibility for acute thrombolytic (rtPA) treatment
  2. Normal brain MRI
  3. Transient ischemic attack or rapidly improving neurological symptoms
  4. Previous disability
  5. Hemorrhagic stroke on brain MRI (T2*/SWI)
  6. Ongoing infection defined by clinical and laboratory signs: an evidence-based guideline will be followed to detect infectious complications (in short, physical and laboratory measures including WBC, ESR, hsCRP, PCT, fever, abnormal urine, chest X-ray or positive cultures)
  7. Diagnosis of malignancy
  8. Known sensitivity to any ingredients in the study drug or radiological contrast material
  9. Participation in another clinical trial within the past 30 days
  10. Stroke in the previous 3 months
  11. Chronic liver, kidney or hematological disease
  12. Contraindications to MRI -Brain aneurysm clip, implanted neural stimulator, implanted cardiac pacemaker or defibrillator, cochlear implant, ocular foreign body e.g. metal shavings, other implanted medical devices: (e.g. Swan Ganz catheter) insulin pump, metal shrapnel or bullet.
  13. Diabetes
  14. Hypertension
  15. Females who are pregnant or breastfeeding

Sites / Locations

  • Inova Health Systems; Inova Fairfax Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Privigen

Normal Saline

Arm Description

The IVIG preparation to be used is 10% liquid (Privigen). IVIG will be applied at a dose of 1.0g/kg, which is approximately 1/2 of the optimal dose used for other immuno/inflammatory indications. The infusion will start at 0.5 ml/kg/hr for the first 30 minutes, to watch for the signs of hypersensitivity to immunoglobulins, and then increased to 2.5 ml/kg/hr, two times slower than the recommended rate indicated in the product package insert (5 ml/kg/hr). Such a low, single dose has not been associated with hyperviscosity and together with a slow infusion will safeguard against occurrence of adverse events related to IVIG infusions. They will receive a total of 1g/kg and depending on patient's weight, it will take between 3.5 to 4+ hours to infuse that amount.

The placebo is the normal saline. Since saline solution will be infused at the volume equivalent to that in which the intended dose of immunoglobulin molecules will be delivered, the placebo (comparator) arm will also serve as a control for the volume of fluid infused to the treatment arm participants.

Outcomes

Primary Outcome Measures

Post-IVIG DWI/PI mismatch measurement
Decrease in the size of post IVIG necrotic area relative to baseline values and percent of penumbra saved, defined by neuroimaging as DWI/PI mismatch.

Secondary Outcome Measures

Favorable clinical outcome
Favorable clinical outcome at Day 90, which requires fulfillment of all three of the following criteria: improvement in NIHSS of 8 points or more from baseline; modified Rankin scale (mRS) score of 0-2 points; and Barthel index (BI) of 75-100
Clinical outcome measure by NIHSS
Clinical outcome measured by change in NIHSS scores will be also examined on Day 3
Active complement fragment levels
Levels of active complement fragments, C3a, C5a, C5b-9 and C4d at Day 0 and post-IVIG and Day 90.
Adverse Events
Incidence in adverse events.

Full Information

First Posted
June 14, 2012
Last Updated
November 7, 2013
Sponsor
Inova Health Care Services
Collaborators
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT01628055
Brief Title
IVIG in Acute Ischemic Stroke: A Pilot Study
Acronym
IVIG/AIS
Official Title
IVIG in Acute Ischemic Stroke: A Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
November 2013
Overall Recruitment Status
Withdrawn
Why Stopped
difficult recruitment and new black box warning for IVIG
Study Start Date
March 2013 (undefined)
Primary Completion Date
August 2013 (Anticipated)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Inova Health Care Services
Collaborators
CSL Behring

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to evaluate the ability of IVIG to affect the rate of progression of brain ischemia, as evidenced by neuroimaging. The results of an ongoing epidemiological study indicate that patients with primary immunodeficiency (PID) on IVIG replacement therapy have an overall prevalence of stroke that is 5 times less than in the general population. Even more striking is the absence of stroke in IVIG-treated PID patients over 65, while in the same general population age group the stroke prevalence goes up to 8.1%. This suggests that the degree of stroke protection correlates with the length of IVIG treatment, since older PID patients have been treated with IVIG significantly longer than younger ones.
Detailed Description
Two pre-clinical studies demonstrated the effectiveness of IVIG preparations in improving the clinical outcome of stroke and at the same time provided evidence of the role of complement fragments in the pathogenesis of ischemia-induced brain damage. Scavenging of these active fragments by IVIG is the likely mechanism of beneficial effect. In one of these studies CSL's own Privigen preparation was used. Considering that it exhibited in-vitro scavenging abilities more pronounced than several other IVIG preparations, and that its in-vivo scavenging capacity was also proven in a relevant animal model, a need to test this preparation in stroke patients is warranted. In addition, activation of complement and the level of activated fragments in humans seem to correlate with the severity of the disease, making them an ideal therapeutic target.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke
Keywords
IVIg, Acute Ischemic Stroke, Stroke, CVA, Cerebrovascular Accident

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Privigen
Arm Type
Experimental
Arm Description
The IVIG preparation to be used is 10% liquid (Privigen). IVIG will be applied at a dose of 1.0g/kg, which is approximately 1/2 of the optimal dose used for other immuno/inflammatory indications. The infusion will start at 0.5 ml/kg/hr for the first 30 minutes, to watch for the signs of hypersensitivity to immunoglobulins, and then increased to 2.5 ml/kg/hr, two times slower than the recommended rate indicated in the product package insert (5 ml/kg/hr). Such a low, single dose has not been associated with hyperviscosity and together with a slow infusion will safeguard against occurrence of adverse events related to IVIG infusions. They will receive a total of 1g/kg and depending on patient's weight, it will take between 3.5 to 4+ hours to infuse that amount.
Arm Title
Normal Saline
Arm Type
Placebo Comparator
Arm Description
The placebo is the normal saline. Since saline solution will be infused at the volume equivalent to that in which the intended dose of immunoglobulin molecules will be delivered, the placebo (comparator) arm will also serve as a control for the volume of fluid infused to the treatment arm participants.
Intervention Type
Biological
Intervention Name(s)
Privigen
Other Intervention Name(s)
IVIg, Immune Globulin Intravenous (Human), Immune Globulin Intravenous (Human), 10% Liquid
Intervention Description
10% liquid intravenous immunoglobulin at a single dose of 1.0g/kg, run at 0.5ml/kg/hr for the first 30 minutes, then increased to 2.5ml/kg/hr until complete (~3-4 hours depending on weight).
Intervention Type
Other
Intervention Name(s)
Normal Saline
Other Intervention Name(s)
0.9% Sodium Chloride Solution
Intervention Description
Normal Saline is a sterile, nonpyrogenic solution for fluid and electrolyte replenishment. It contains no antimicrobial agents. The pH is 5.0 (4.5 to 7.0). It contains 9 g/L Sodium Chloride with an osmolarity of 308 mOsmol/L and 154 mEq/L Sodium and Chloride. The infusion will start at 0.5 ml/kg/hr for the first 30 minutes and then increased to 2.5 ml/kg/hr for 3-4 hours.
Primary Outcome Measure Information:
Title
Post-IVIG DWI/PI mismatch measurement
Description
Decrease in the size of post IVIG necrotic area relative to baseline values and percent of penumbra saved, defined by neuroimaging as DWI/PI mismatch.
Time Frame
3 days
Secondary Outcome Measure Information:
Title
Favorable clinical outcome
Description
Favorable clinical outcome at Day 90, which requires fulfillment of all three of the following criteria: improvement in NIHSS of 8 points or more from baseline; modified Rankin scale (mRS) score of 0-2 points; and Barthel index (BI) of 75-100
Time Frame
90 days
Title
Clinical outcome measure by NIHSS
Description
Clinical outcome measured by change in NIHSS scores will be also examined on Day 3
Time Frame
3 days
Title
Active complement fragment levels
Description
Levels of active complement fragments, C3a, C5a, C5b-9 and C4d at Day 0 and post-IVIG and Day 90.
Time Frame
90 days
Title
Adverse Events
Description
Incidence in adverse events.
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Onset of neurological symptoms between 4.5 and 8 hours Male or Female age 45 -75 years old Score of 10-15 points on the National Institutes of Health Stroke Scale (NIHSS) with clinical signs suggestive of ischemic stroke Acute brain ischemia with a distinct penumbra (at least 20%), measured by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI), in the territory of the middle cerebral artery, anterior cerebral artery, or posterior cerebral artery with a hemispheric distribution Ability and willingness to provide informed consent and comply with study requirements and procedures Exclusion Criteria: Eligibility for acute thrombolytic (rtPA) treatment Normal brain MRI Transient ischemic attack or rapidly improving neurological symptoms Previous disability Hemorrhagic stroke on brain MRI (T2*/SWI) Ongoing infection defined by clinical and laboratory signs: an evidence-based guideline will be followed to detect infectious complications (in short, physical and laboratory measures including WBC, ESR, hsCRP, PCT, fever, abnormal urine, chest X-ray or positive cultures) Diagnosis of malignancy Known sensitivity to any ingredients in the study drug or radiological contrast material Participation in another clinical trial within the past 30 days Stroke in the previous 3 months Chronic liver, kidney or hematological disease Contraindications to MRI -Brain aneurysm clip, implanted neural stimulator, implanted cardiac pacemaker or defibrillator, cochlear implant, ocular foreign body e.g. metal shavings, other implanted medical devices: (e.g. Swan Ganz catheter) insulin pump, metal shrapnel or bullet. Diabetes Hypertension Females who are pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Beverly C Walters, MD
Organizational Affiliation
Inova Health Systems
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Milan Basta, MD
Organizational Affiliation
BioVisions, Inc.
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jack Cochran, MD
Organizational Affiliation
Inova Health Systems
Official's Role
Principal Investigator
Facility Information:
Facility Name
Inova Health Systems; Inova Fairfax Hospital
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States

12. IPD Sharing Statement

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IVIG in Acute Ischemic Stroke: A Pilot Study

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