Phase III Randomized, Double-Blind, Sham-Controlled Study of Plasma Exchange for Acute Severe Attacks of Inflammatory Demyelinating Disease Refractory to Intravenous Methylprednisolone

National Institutes of Health (NIH)

Status and phase: Unknown; Phase 3

Conditions: Balo's Concentric Sclerosis; Devic's Syndrome; Marburg's Variant of Multiple Sclerosis; Acute Transverse Myelitis; Acute Disseminated Encephalomyelitis

Treatments: Procedure: Plasma exchange

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00004645

MAYOC-29493

199/11693

Details and patient eligibility

About

OBJECTIVES:

I. Evaluate the effectiveness of plasma exchange in the treatment of acute severe attacks of inflammatory demyelinating disease in patients who have failed intravenous steroid therapy.

Full description

PROTOCOL OUTLINE: This is a randomized, double-blind study. Patients are stratified by disease type; each stratum is randomized separately.

The first group of patients receives a true plasma exchange using continuous-flow centrifugation with serum albumin and crystalloid replacement every 2 days for a total of 7 exchanges.

The second group receives a sham plasma exchange with no centrifugation every 2 days for a total of 7 exchanges.

Patients cross to the alternate therapy if there is less than a moderate improvement by day 14. The treatment decision is based on a blinded neurologic assessment.

Concurrent corticosteroids and other immunosuppressants, and high-dose barbiturates are not allowed.

Patients are followed at 1 and 6 months after the last exchange.

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Idiopathic inflammatory demyelinating syndrome, as follows: biopsy-proven if necessary - established diagnosis of multiple sclerosis (MS) using Poser criteria; acute disseminated encephalomyelitis; Marburg's variant of MS Balo's concentric sclerosis
• Eligible without biopsy: acute transverse myelitis; Devic's syndrome
• Acute neurologic deficit markedly affecting consciousness, language, or brainstem/spinal cord function, i.e., aphasia, paraplegia, coma, quadriplegia, hemiplegia, severe organic brain syndrome
• Deficit unresponsive to 5 days of high-dose intravenous methylprednisolone (MePRDL), as follows: deficit duration of 21 days to 3 months AND no improvement 14 days after beginning MePRDL OR deficit duration of 12 to 20 days AND continued deterioration after completion of MePRDL
• No chronically progressive demyelinating disease
• No HIV-associated demyelinating syndrome
• No progressive multifocal leukoencephalopathy
• No optic neuritis

--Prior/Concurrent Therapy--

• No more than 3 months of prior steroid therapy Failure on prior MePRDL required Minimum dose 7 mg/kg per day for 5 days
• At least 6 weeks since other immunosuppressives, e.g., cyclophosphamide, azathioprine, cyclosporine

--Patient Characteristics--

• Renal: Creatinine less than 1.5 mg/dL
• Cardiovascular: No hypovolemia; no infarction; no vasculitis; no other major systemic cardiovascular illness
• Pulmonary: No major respiratory illness
• Other: No infection, including hepatitis or human immunodeficiency virus; no recent intravenous drug abuse; no high-risk sexual behavior; no cardiac, cerebrovascular, or autonomic dysfunction that would increase risk of hypotension; no other major systemic illness that would preclude protocol therapy; no pregnant or nursing women; negative serum pregnancy test required of fertile women; effective contraception required