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

Inova Health Care Services

Status and phase: Withdrawn; Phase 1

Conditions: Ischemic Stroke

Treatments: Other: Normal Saline; Biological: Privigen

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01628055

IVIG/AIS-IFH-MB-CSL

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 45 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

Privigen

Experimental group

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.

Treatment:

Biological: Privigen

Normal Saline

Placebo Comparator group

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.

Treatment:

Other: Normal Saline