Proof-of-Concept: A Pilot, Randomized, Double-Blind Study of Oseltamivir Versus Placebo for Immune Thrombocytopenia
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|ClinicalTrials.gov Identifier: NCT03520049|
Recruitment Status : Unknown
Verified October 2020 by Unity Health Toronto.
Recruitment status was: Recruiting
First Posted : May 9, 2018
Last Update Posted : October 22, 2020
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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.
|Condition or disease||Intervention/treatment||Phase|
|Immune Thrombocytopenia||Drug: Oseltamivir Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Proof of Concept; A Pilot, Randomized, Double-Blind Study of Oseltamivir Versus Placebo for Immune Thrombocytopenia|
|Actual Study Start Date :||November 2016|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||September 2021|
Oseltamivir capsule administered orally at 75 mg twice daily for five consecutive days.
Placebo Comparator: Placebo
Placebo capsule administered orally twice daily for five consecutive days.
- Mean platelet glycoprotein sialyation [ Time Frame: Day 0 and Day 5 ]Mean platelet glycoprotein sialyation
- Percentage of eligible patients successfully recruited [ Time Frame: Screening and Day 0 ]Determine the percent of eligible patients that successfully enrolled in the study.
- Number of patients recruited per month [ Time Frame: Screening and Day 0 ]Number of patients recruited per month
- Percentage of patients who received the study drug within 12 hours of randomization [ Time Frame: Day 0 ]Percentage of patients who received the study drug within 12 hours of randomization
- Percentage of patients who received every scheduled dose of the study drug in a blinded fashion [ Time Frame: Day 0 and Day 5 ]Study drug will be dispensed on Day 0 and study drug administration will be assessed on Day 5 by reviewing the blister pack and patient diary
- Percentage of patients who had complete follow-up 12 months after randomization [ Time Frame: Day 0, Day 5 and Follow up ]Proportion of patients that completed follow-up 12 months after randomization out of the total number of participants that were randomized.
- Mean platelet count [ Time Frame: Day 0, Day 5 and Follow up ]Mean platelet count
- Proportion of patients who received additional ITP based therapy during the study follow-up period [ Time Frame: Day 0, Day 5 and Follow up ]Proportion of patients who received additional ITP based therapy during the study follow-up period
- Frequencies of CD4+ and CD8+ T regulatory cells [ Time Frame: Day 0 and Day 14 ]Frequencies of CD4+ and CD8+ T regulatory cells
- Cytokine profiles [ Time Frame: Day 0 and Day 14 ]Cytokine profiles
- Anti-platelet glycoprotein antibody specificity/titer [ Time Frame: Day 0 and Day 14 ]Anti-platelet glycoprotein antibody specificity/titer
- Effects of antibodies on macrophage- and hepatocyte-mediated Fc-dependent and independent phagocytosis in vitro [ Time Frame: Day 0 and Day 14 ]Effects of antibodies on macrophage- and hepatocyte-mediated Fc-dependent and independent phagocytosis in vitro
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Patients ≥ 18 years of age;
- Patients with primary or secondary (i.e. ITP due to a secondary cause) ITP (autoimmune disorder characterized by isolated thrombocytopenia with no other causes or disorders that can be associated with thrombocytopenia; diagnosis of exclusion);
- Individuals with lack of sustained complete remission - platelet count <100 x E9/L despite first line therapy (prednisone, dexamethasone, IVIG);
- Patient's median platelet count over the last 12 months is <100 x E9/L, and must be <100 x E9/L on screening day.
- Concurrent medical or surgical treatment for ITP (e.g. prednisone, dexamethasone, IVIG, anti-RhD immune globulin, azathioprine, cyclosporine, cyclophosphamide, danazol, dapsone, mycophenylate mofetil, rituximab, thrombopoietin mimetics, any investigational agents for ITP, splenectomy);
- Patient with a platelet count of <20 x E9/L with active significant bleeding based on a bleeding assessment score of Grade 2 at any site by the ITP Bleeding Scale (IBLS);
- Any immunosuppressive or immunomodulating therapy (not aforementioned) over the last 3 months;
- Oseltamivir therapy over the last 3 months;
- Pregnant females (oseltamivir is a class C drug in pregnancy);
- Lactating females (oseltamivir is detected in low quantities in breast milk).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03520049
|St. Michael's Hospital||Recruiting|
|Toronto, Ontario, Canada, M5B 1W8|
|Contact: Michelle Sholzberg, MDCM, MSc 416-864-5389 SholzbergM@smh.ca|
|Principal Investigator: Michelle Sholzberg, MDCM, MSc|
|Principal Investigator: Heyu Ni, MD, PhD, MSc|
|Sub-Investigator: Andreas Laupacis, MD, MSc|
|Sub-Investigator: Kevin Thorpe, MMath|
|Sub-Investigator: Gloria Lim, MD, MSc|
|Responsible Party:||Unity Health Toronto|
|Other Study ID Numbers:||
|First Posted:||May 9, 2018 Key Record Dates|
|Last Update Posted:||October 22, 2020|
|Last Verified:||October 2020|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||No|
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Blood Coagulation Disorders
Immune System Diseases
Molecular Mechanisms of Pharmacological Action