"Dallas WITS: West Nile Virus Interferon Treatment Study"

Summary

The study will be a multi-center randomized, double-blinded, placebo-controlled trial comparing interferon alpha 2b vs placebo in the treatment of WNV neuroinvasive disease.. The lead center will be the University of Texas Southwestern Medical Center and participating centers will join as soon as their IRBs grant approval. This is a pilot estimation study, as there is scarce data about the number of patients with flaviviral neuroinvasive disease treated with interferon alpha, so we are estimating a probably need for 80 patients (40 randomized to each treatment arm). Patients will be identified for potential recruitment at each facility by daily review of CSF analysis from the microbiology and chemistry lab. The case definition for inclusion in the study will require: CSF pleocytosis (≥10 WBC per mm3), negative gram stain, and two signs consistent with WNV neuroinvasive disease (such as fever, headache, altered mental status, seizures, flaccid paralysis) with no other immediate explanation for the clinical presentation. As pre-clinical studies show improved efficacy with earlier treatment and the disease is currently epidemic in Dallas, with varying turn-around times for WNV antibody testing in CSF and serum, a CSF WNV IgM result will not be required prior to enrollment. This was the case in the Rahal study as during progression of the outbreak patients were enrolled who fit the clinical criteria pending serologic studies.20 Patients who subsequently have negative serum WNV IgM will be withdrawn from the study. Patients must be enrolled within 5 days of symptom onset or hospitalization to avoid randomization of patients with potentially irreversible CNS disease. Patients will be randomized by the Department of Biostatistics at the University of Texas Southwestern Medical Center to receive either interferon alpha 2b or placebo with blinding of the investigators and patients.

Study drugs will be prepared independently at each participating institution and patients receiving the study drug will be administered interferon alpha 2b, 3 million units as an intravenous loading dose, followed by 3 million units subcutaneous 12 hours later, then 3 million units subcutaneous daily for six days to complete 8 total doses. This dosing protocol is based on in vitro and PK data as described above. Patients receiving placebo will be administered normal saline in the same manner.

Participant Eligibility

The population in this study will include any patient 18 years of age or older, male
or female, of any race who meets the following criteria:

- Admitted to the University Hospital – St. Paul or Zale Lipshy, Presbyterian Hospital , Baylor Hospital and Parkland Hospital during the 2012 WNV season defined by the Texas Department of Health and Human Services – August through November 1, 2012 with:

- CSF abnormalities (CSF pleocytosis and/or elevated protein, absence of organisms on gram stain, AFB or fungal stain) and two or more of the following symptoms or signs: fever, headache, altered mental status, or focal neurologic signs (focal sensory changes, paralysis, seizure, respiratory insufficiency, extra-pyramidal symptoms, or new motor weakness).

- Requirement of a positive serum and/or CSF test for WNV IgM antibody prior to enrollment will be waived in this epidemic situation. Patients who are randomized and subsequently test negative for serum WNV IgM will be withdrawn from the study.

- Patients must be enrolled within 5 days of symptom onset in order to avoid randomization of potentially irreversible, advanced central nervous system disease and because of poor efficacy in animal studies when administered late in the disease course. Patients unable to provide a date of symptom onset must be enrolled within 5 days of hospitalization.