IVIG in Acute Ischemic Stroke: A Pilot Study

NCT01628055 | Withdrawn Phase 1

• 1 other identifier: IVIG/AIS-IFH-MB-CSL
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemic Stroke

Keywords

IVIg; Acute Ischemic Stroke; Stroke; CVA; Cerebrovascular Accident

Outcome Measures

Primary Outcomes (1)

• 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.

  3 days

Secondary Outcomes (4)

• Favorable clinical outcome

  90 days

• Clinical outcome measure by NIHSS

  3 days

• Active complement fragment levels

  90 days

• Adverse Events

  90 days

Study Arms (2)

Privigen

EXPERIMENTAL

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

Normal Saline

PLACEBO COMPARATOR

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

Interventions

Privigen BIOLOGICAL

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).

Also known as: IVIg, Immune Globulin Intravenous (Human), Immune Globulin Intravenous (Human), 10% Liquid

Privigen

Normal Saline OTHER

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.

Also known as: 0.9% Sodium Chloride Solution

Normal Saline

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Inova Health Care Services: lead
• CSL Behring: collaborator

Study Sites (1)

Inova Health Systems; Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Related Publications (34)

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MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Immunoglobulins, Intravenous; gamma-Globulins; Fluid Therapy; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Therapy; Therapeutics; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Beverly C Walters, MD

  Inova Health Systems

  STUDY DIRECTOR

• Milan Basta, MD

  BioVisions, Inc.

  STUDY CHAIR

• Jack Cochran, MD

  Inova Health Systems

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 26, 2012
• Study Start: March 1, 2013
• Primary Completion: August 1, 2013
• Study Completion: September 1, 2013
• Last Updated: November 11, 2013

Record last verified: 2013-11

Locations

US (1)