phase iii randomized, double-blind, sham-controlled study of plasma exchange for acute severe attacks of inflammatory demyelinating disease refractory to intravenous methylprednisolone

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

Summary: 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.

Eligibility 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

Keywords: balo's concentric sclerosis devic's syndrome marburg's variant of multiple sclerosis acute disseminated encephalomyelitis acute transverse myelitis multiple sclerosis neurologic and psychiatric disorders rare disease