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

This study has been withdrawn prior to enrollment.
(difficult recruitment and new black box warning for IVIG)
Sponsor:
Collaborator:
CSL Behring
Information provided by (Responsible Party):
Inova Health Care Services
ClinicalTrials.gov Identifier:
NCT01628055
First received: June 14, 2012
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Ischemic Stroke
Biological: Privigen
Other: Normal Saline
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: IVIG in Acute Ischemic Stroke: A Pilot Study

Resource links provided by NLM:


Further study details as provided by Inova Health Care Services:

Primary Outcome Measures:
  • Post-IVIG DWI/PI mismatch measurement [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    Clinical outcome measured by change in NIHSS scores will be also examined on Day 3

  • Active complement fragment levels [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Levels of active complement fragments, C3a, C5a, C5b-9 and C4d at Day 0 and post-IVIG and Day 90.

  • Adverse Events [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    Incidence in adverse events.


Enrollment: 0
Study Start Date: March 2013
Study Completion Date: September 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Privigen
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.
Biological: Privigen
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).
Other Names:
  • IVIg
  • Immune Globulin Intravenous (Human)
  • Immune Globulin Intravenous (Human), 10% Liquid
Placebo Comparator: Normal Saline
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.
Other: Normal Saline

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.

Other Name: 0.9% Sodium Chloride Solution

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.

  Eligibility

Ages Eligible for Study:   45 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01628055

Locations
United States, Virginia
Inova Health Systems; Inova Fairfax Hospital
Falls Church, Virginia, United States, 22042
Sponsors and Collaborators
Inova Health Care Services
CSL Behring
Investigators
Study Director: Beverly C Walters, MD Inova Health Systems
Study Chair: Milan Basta, MD BioVisions, Inc.
Principal Investigator: Jack Cochran, MD Inova Health Systems
  More Information

Publications:

Responsible Party: Inova Health Care Services
ClinicalTrials.gov Identifier: NCT01628055     History of Changes
Other Study ID Numbers: IVIG/AIS-IFH-MB-CSL
Study First Received: June 14, 2012
Last Updated: November 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Inova Health Care Services:
IVIg
Acute Ischemic Stroke
Stroke
CVA
Cerebrovascular Accident

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Pathologic Processes
Immunoglobulins
Antibodies
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014