A Trial of Eltrombopag or Intravenous Immune Globulin Before Surgery for Immune Thrombocytopenia Patients

Condition(s) targeted: Immune Thrombocytopenic Purpura

Intervention: Eltrombopag (Drug); IVIG infusion (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: McMaster University

Official(s) and/or principal investigator(s):
Donald M Arnold, MD MSc, Principal Investigator, Affiliation: McMaster University

Overall contact:
Donald M Arnold, MD, Phone: 905-521-2100, Ext: 76305, Email: arnold@mcmaster.ca

This is a study to investigate if eltrombopag can be used instead of Intravenous Immune Globulin (IVIG) in patients with ITP, to adequately raise their platelet count when they undergo minor or major surgery. Eltrombopag is a daily, oral pill approved for treatment of ITP. IVIG is a blood product frequently used to treat ITP. Patients with ITP who need surgery have to get treatment to increase their platelet count. IVIG is commonly used for this purpose but eltrombopag may be more effective and convenient for patients.

Official title: Treatment of thromBocytopenia With EltRombopag or Intravenous Immune Globulin (IVIG) Before and DurING Invasive Procedures in Patients With Immune ThrombocytoPenia- BRIDGING ITP Study

Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Primary outcome: Proportion of patients achieving the platelet count threshold before surgery and maintaining platelet counts within the target range without the use of ITP rescue treatment.

Secondary outcome:

Time to treatment failure

Bleeding

Proportion of participants who undergo surgery as planned

Treatment satisfaction assessment

Use of blood transfusions

Pre-surgery platelet count change from baseline

Total clinic and hospital days

Venous thromboembolism and arterial thromboembolism

Adverse Events

Detailed description: Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease characterized by the presence of platelet autoantibodies, low platelet counts and an increased risk of bleeding. TPO receptor agonists which stimulate platelet production have been shown to be remarkably effective in ITP. Their use as a short-term means of elevating platelet counts in preparation for surgical procedures has not yet been adequately evaluated. Many patients with moderate to severe ITP (platelet count less than 50 x 10exp9/L) have stable platelet counts and do not bleed; however, when surgeries or invasive procedures become necessary, additional treatment is often required to increase the platelet count to achieve adequate hemostasis. Although specific guidelines for surgical platelet count thresholds in ITP are lacking, platelet transfusion guidelines recommend a platelet count of

50 - 100 x10exp9/L for the vast majority of surgical procedure; 50x10exp9/L is a typical

threshold for minor surgeries like tooth extractions and endoscopies; and 100x10exp9/L is used for major surgery like cardiac surgery or neurosurgery. Commonly, intravenous immunoglobulin (IVIG) is used to rapidly increase platelet counts in ITP patients before an invasive procedure. IVIG is associated with a transient platelet

count response in approximately 80% of patients, which occurs within 2 - 4 days. In most

patients, platelet counts remain elevated for approximately 4 weeks, allowing enough time to complete the procedure and for adequate post-operative hemostasis. However, IVIG is a resource-intensive and expensive blood product associated with frequent side effects. Eltrombopag is a small molecule, non-peptide thrombopoietin (TPO) receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. TPO receptor agonists are an effective new class of medications that are non-immunogenic agonists of the TPO receptor (c-Mpl) and work by increasing platelet production in ITP patients. In randomized controlled trials, eltrombopag maintenance therapy has been shown to raise the

platelet count in 60 - 80% of ITP patients and platelet counts generally remain elevated as

long as the drug is continued. Time to response is 1 - 2 weeks with minimal need for dose

titration. Side effects of eltrombopag observed in clinical studies included elevation of liver enzymes (approximately 10% of patients). The risk of thrombosis and bone marrow reticulin formation remain uncertain. The investigators propose a randomized controlled trial (RCT) involving 74 patients (across approximately 8 centers) in Canada. This study will evaluate the efficacy and safety of eltrombopag bridging therapy compared with IVIG bridging therapy in adult patients with ITP who require surgery. This study will also evaluate bleeding, adverse events and patient-reported treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM). Patients will be stratified according to centre and surgery type (major vs. minor).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Primary or secondary ITP;

- Platelet count below surgical platelet count threshold (50 x10exp9/L for minor

surgery; 100 x 10exp9/L for major surgery);

- 18 years of age or older;

- On stable doses of concomitant ITP medications (i. e the dose administered has not

changed),excluding IVIG and thrombopoietin receptor agonists, or no ITP medication in the past 2 weeks;

- At least 3-weeks lead time available between randomization and scheduled surgery;

- IVIG and Eltrombopag are acceptable ITP treatment options for this patient;

- Able to provide informed consent.

Exclusion Criteria:

- Pregnancy or breastfeeding;

- Treatment with IVIG within the last 2 weeks;

- Treatment with a thrombopoietin receptor agonist (eltrombopag or romiplostim) within

the last 4 weeks;

- Known previous IVIG treatment failure (defined as the lack of a platelet count

doubling from baseline and increase above 50 x10exp9/L by 2 weeks);

- Known previous thrombopoietin receptor agonist treatment failure (defined as the lack

of a platelet count doubling from baseline and increase above 50 x10exp9/L by 2 weeks)

- AST, ALT above 2X upper limit of normal;

- Bilirubin above 1. 5X upper limit of normal;

- Deep vein thrombosis, myocardial infarction, thrombotic stroke or arterial thrombosis

in the last 12 months;

- History of bone marrow reticulin or fibrosis;

- Known liver cirrhosis;

- Active malignancy (defined as requiring treatment or palliation within the last 6

months);

- Any additional laboratory test result, health related illness or other diagnosis

which, in the opinion of the treating physician, may put the subject's health or safety at risk.

Donald M Arnold, MD, Phone: 905-521-2100, Ext: 76305, Email: arnold@mcmaster.ca

University of Alberta Hospital, Edmonton, Alberta T6G2G3, Canada; Recruiting
Loree Larratt, MD, Phone: 780-407-7021, Email: loree.larratt@ualberta.ca
Donna Perez, Phone: 780-407-6090, Email: Donna.Perez@albertahealthservices.ca
Loree Laratt, MD, Principal Investigator
Irwindeep Sandhu, MD, Sub-Investigator

Vancouver General Hospital, Vancouver, British Columbia V5Z1M9, Canada; Recruiting
Leslie Zypchen, MD, Phone: 604-875-5270, Email: lzypchen@bccancer.bc.ca
Jill Clark, Phone: 604-875-4111, Ext: 62887, Email: jclark2@bccancer.bc.ca
Leslie Zypchen, MD, Principal Investigator

Hamilton Health Sciences, Hamilton, Ontario L8N 3Z5, Canada; Recruiting
Donald M Arnold, MD, Phone: 905-521-2100, Ext: 76305, Email: arnold@mcmaster.ca
Korinne Hamilton, Phone: 905-521-2100, Ext: 73821, Email: khamil@mcmaster.ca
Donald M Arnold, MD, Principal Investigator

London Health Sciences Center, London, Ontario N6A5W9, Canada; Recruiting
Cyrus Hsia, MD, Phone: 519-685-8500, Ext: 56060, Email: cyrus.hsia@lhsc.on.ca
Laura Meraw, Phone: 519-685-8500, Ext: 57135, Email: Laura.Meraw@lhsc.on.ca
Cyrus Hsia, MD, Principal Investigator

Ottawa Hospital, Ottawa, Ontario K1H8L6, Canada; Recruiting
Alan Tinmouth, MD, Phone: 613-737-8899, Ext: 73914, Email: Atinmouth@Ottawahospital.on.ca
Elizabeth Chatelain, Phone: 613-737-8899, Ext: 71264, Email: echatelain@ohri.ca
Alan Tinmouth, MD, Principal Investigator

St.Micheal's Hospital, Toronto, Ontario M5B1W8, Canada; Not yet recruiting
Michelle Sholzberg, MD, Phone: 416-864-6060, Email: SholzbergM@smh.ca
Lisa Faure, Phone: 416-864-6060, Ext: 2084, Email: faurei@smh.ca
Michelle Sholzberg, MD, Principal Investigator

Sunnybrook Hospital, Toronto, Ontario M4N3M5, Canada; Recruiting
Yulia Lin, MD, Phone: 416-480-6100, Ext: 2781, Email: Yulia.Lin@sunnybrook.ca
Yulia Lin, MD, Principal Investigator

Hopital Maisonneuve-Rosemont, Montreal, Quebec H1T2M4, Canada; Recruiting
Jeannine Kassis, MD, Phone: 514-252-3404, Email: jkassis.hmr@ssss.gouv.qc.ca
Julie Trinh Lu, B.Sc, DESS, Phone: 514-252-3400, Ext: 3336, Email: jtlu.hmr@ssss.gouv.qc.ca
Jeannine Kassis, MD, Principal Investigator

Jewish General Hospital, Montreal, Quebec H3T1E2, Canada; Recruiting
Mark Blostein, MD, Phone: 514-340-8214, Email: mark.blostein@mgill.ca
Vivian Pananis, Phone: 514-340-8222, Ext: 5982, Email: vpananis@gmail.com
Mark Blostein, MD, Principal Investigator

Starting date: October 2012
Last updated: April 7, 2015