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

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.

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.

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

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

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• Mayo Clinic