IVIG in Acute Ischemic Stroke: A Pilot Study

Ischemic Stroke Clinical Trial

— IVIG/AIS  

Official title:

IVIG in Acute Ischemic Stroke: A Pilot Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01628055
• Other study ID #: IVIG/AIS-IFH-MB-CSL
• Status: Withdrawn
• Phase: Phase 1
• First received: June 14, 2012
• Last updated: November 7, 2013
• Start date: March 2013
• Est. completion date: September 2013

Study information

• Verified date: November 2013
• Source: Inova Health Care Services
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemia
• Ischemic Stroke
• Stroke

Intervention

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:
• 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.

Locations

Country	Name	City	State
United States	Inova Health Systems; Inova Fairfax Hospital	Falls Church	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Inova Health Care Services	CSL Behring

Country where clinical trial is conducted

United States, 

References & Publications (34)

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* Note: There are 34 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	90 days	No
Secondary	Clinical outcome measure by NIHSS	Clinical outcome measured by change in NIHSS scores will be also examined on Day 3	3 days	No
Secondary	Active complement fragment levels	Levels of active complement fragments, C3a, C5a, C5b-9 and C4d at Day 0 and post-IVIG and Day 90.	90 days	No
Secondary	Adverse Events	Incidence in adverse events.	90 days	Yes