A Trial of Eltrombopag or Intravenous Immune Globulin Before Surgery for Immune Thrombocytopenia Patients
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|ClinicalTrials.gov Identifier: NCT01621204|
Recruitment Status : Recruiting
First Posted : June 18, 2012
Last Update Posted : April 7, 2017
|Condition or disease||Intervention/treatment||Phase|
|Immune Thrombocytopenic Purpura||Drug: Eltrombopag Drug: IVIG infusion||Phase 3|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||74 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Investigator, Outcomes Assessor)|
|Primary Purpose:||Supportive Care|
|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 Start Date :||October 2012|
|Estimated Primary Completion Date :||August 2018|
|Estimated Study Completion Date :||August 2018|
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.
Participants are started on 50mg daily oral pill (or 25mg daily for patients of East Asian descent) as of 21 days before surgery. Dose may be adjusted based on platelet count monitoring (minimum 25mg; maximum 75mg).
Other Name: Revolade
Active Comparator: IVIG infusion
Intravenous immunoglobulin (IVIG) is used to rapidly increase platelet counts in ITP patients. IVIG is associated with a transient platelet count response in approximately 80% of patients, which occurs within 2 - 4 days. It is commonly used to improve platelet count numbers prior to surgery for patients with ITP.
Drug: IVIG infusion
IVIG infusion (2 g/kg, over 2 days) given 7 (+/-2) days prior to surgery and additional infusions given as needed until 7 days after surgical hemostasis is achieved.
- 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. [ Time Frame: For a the period of time from surgery until 7 days after surgical hemostasis is achieved (average duration is 7 days) ]Hemostasis will be assessed daily after surgery. The main outcome measure (platelet count above threshold) will be evaluated 7 days after hemostasis is achieved.
- Time to treatment failure [ Time Frame: During the period from surgery until 7 days after surgical hemostasis is acehieved ]
- Bleeding [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]
- Proportion of participants who undergo surgery as planned [ Time Frame: Measured at time of planned surgery (2 week for IVIG; 3 weeks for eltrombopag) ]
- Treatment satisfaction assessment [ Time Frame: Assessed immediately before surgery (Day -2) and at 4 weeks (average for IVIG) or 5 weeks (average for eltrombopag). ]Treatment satisfaction assessed on Day -2 +/-1 day and once during follow up using the Treatment Satisfaction Questionnaire for Medications Score (which incorporates effectiveness, convenience, side effects, and overall satisfaction)
- Use of blood transfusions [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]Platelet, red blood cells and plasma transfusions
- Pre-surgery platelet count change from baseline [ Time Frame: Measured immediately before surgery (3 weeks, average for eltrombopag; 2 weeks, average for IVIG) ]Includes platelet change from baseline, proportion of pts who have a platelet count greater than 400x10exp9/L pre and post surgery, proportion of pts who have a platelet count less than 50x10exp9/L (minor surgery) or 100x10exp9/L (major surgery)
- Total clinic and hospital days [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]Number of days participant spends at clinic appointments and number of days hospitalized
- Venous thromboembolism and arterial thromboembolism [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]Rare known adverse event with eltrombopag
- Adverse Events [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]
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): NCT01621204
|Contact: Donald M Arnold, MD||905-521-2100 ext email@example.com|
|Contact: Julie B Carruthers, MLT||905-525-9140 ext firstname.lastname@example.org|
|University of Alberta Hospital||Recruiting|
|Edmonton, Alberta, Canada, T6G2G3|
|Contact: Loree Larratt, MD 780-407-7021 email@example.com|
|Contact: Donna Perez 780-407-6090 Donna.Perez@albertahealthservices.ca|
|Principal Investigator: Loree Laratt, MD|
|Sub-Investigator: Irwindeep Sandhu, MD|
|Canada, British Columbia|
|Vancouver General Hospital||Terminated|
|Vancouver, British Columbia, Canada, V5Z1M9|
|Hamilton Health Sciences||Recruiting|
|Hamilton, Ontario, Canada, L8N 3Z5|
|Contact: Donald M Arnold, MD 905-525-9140 ext 28603 firstname.lastname@example.org|
|Contact: Erin Jamula, MSc 905-525-9140 ext 21845 email@example.com|
|Principal Investigator: Donald M Arnold, MD|
|London Health Sciences Center||Recruiting|
|London, Ontario, Canada, N6A5W9|
|Contact: Cyrus Hsia, MD 519-685-8500 ext 56060 firstname.lastname@example.org|
|Contact: Laura Meraw 519-685-8500 ext 57135 Laura.Meraw@lhsc.on.ca|
|Principal Investigator: Cyrus Hsia, MD|
|Ottawa, Ontario, Canada, K1H8L6|
|Contact: Alan Tinmouth, MD 613-737-8899 ext 73914 Atinmouth@Ottawahospital.on.ca|
|Contact: Elizabeth Chatelain 613-737-8899 ext 71264 email@example.com|
|Principal Investigator: Alan Tinmouth, MD|
|Toronto, Ontario, Canada, M4N3M5|
|Contact: Yulia Lin, MD 416-480-6100 ext 2781 Yulia.Lin@sunnybrook.ca|
|Principal Investigator: Yulia Lin, MD|
|Toronto, Ontario, Canada, M5B1W8|
|Contact: Michelle Sholzberg, MD 416-864-6060 SholzbergM@smh.ca|
|Contact: Aziz Jiwajee 416-864-5354 JiwajeeA@smh.ca|
|Principal Investigator: Michelle Sholzberg, MD|
|Montreal, Quebec, Canada, H1T2M4|
|Contact: Jeannine Kassis, MD 514-252-3404 firstname.lastname@example.org|
|Contact: Julie Trinh Lu, B.Sc, DESS 514-252-3400 ext 3336 email@example.com|
|Principal Investigator: Jeannine Kassis, MD|
|Jewish General Hospital||Recruiting|
|Montreal, Quebec, Canada, H3T1E2|
|Contact: Mark Blostein, MD 514-340-8214 firstname.lastname@example.org|
|Contact: Vivian Pananis 514-340-8222 ext 5982 email@example.com|
|Principal Investigator: Mark Blostein, MD|
|Principal Investigator:||Donald M Arnold, MD MSc||McMaster University|