OseltamivirProof-of-Concept: A Pilot, Randomized, Double-Blind Study of Oseltamivir Versus Placebo for Immune Thrombocytopenia

Immune Thrombocytopenia (ITP) is a disorder resulting in impaired platelet production and enhanced destruction on the basis of autoantibody-mediated mechanisms. Patients with ITP are at increased risk of bleeding and infection. First line therapy includes glucocorticoids, with or without the addition of intravenous immune globulin (IVIg) when a prompt platelet response is desired. The likelihood of stable and safe disease after first-line treatment ranges from 30-60% and risk of relapse requiring additional therapy occurs in 50-80% of patients. Moreover, the toxicity associated with first and subsequent therapy for ITP is substantial.

Oseltamivir is an attractive drug for ITP since it specifically targets a pathophysiologic mechanism that appears to be important for the development of ITP and has a benign side effect profile compared to standard ITP therapy.

Oseltamivir has never been rigorously tested in humans to determine its efficacy in the management of ITP. The investigators therefore propose the first randomized, double blind study to assess the impact of oseltamivir on biological markers in adult patients with ITP. This study will also provide information about the feasibility of recruitment into a definitive trial, which would be coordinated by St. Michael's Hospital.

The research question is: Do adults (≥ 18 years) with ITP treated with oseltamivir at 75mg twice daily for 5 consecutive days have an increase in their mean platelet glycoprotein sialylation compared to those receiving placebo?

This pilot, proof-of-concept, randomized controlled clinical trial will enroll 30 individuals with ITP. Randomization and allocation will occur at a ratio of 1:1. Analysis of the primary outcome measure will occur via analysis of covariance (ANCOVA).

This study has the potential to dramatically change the treatment of ITP. If the results from this study demonstrate a biological effect, and results from the subsequent definitive study are positive, The investigators envision a move away from non-specific immune-blunting therapy such as prednisone, towards tailored therapy with oseltamivir. It could diminish the lifelong summative immunosuppressive therapy burden, associated drug toxicity and improve long- and short-term health outcomes for these patients.