A Trial of Eltrombopag or Intravenous Immune Globulin Before Surgery for Immune Thrombocytopenia Patients
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| ClinicalTrials.gov Identifier: NCT01621204 |
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Recruitment Status :
Recruiting
First Posted : June 18, 2012
Last Update Posted : June 18, 2018
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| 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 |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| 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 : | January 2019 |
| Estimated Study Completion Date : | January 2019 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Eltrombopag
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.
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Drug: Eltrombopag
Participants are started on 50mg daily oral pill (or 25mg daily for patients of East Asian descent) 21 days before surgery. Dose may be adjusted based on subsequent platelet counts (minimum 25mg; maximum 75mg).
Other Name: Revolade |
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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.
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Drug: IVIG infusion
IVIG infusion (1-2 g/kg) given 7 (+/-2) days prior to surgery; with an additional infusion allowed within one week of achievement of surgical hemostasis, if needed
Other Names:
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- Achievement of a platelet count level that is above the platelet count threshold for surgery preoperatively and that is maintained above the threshold during the post-hemostasis period without the use of rescue treatment [ Time Frame: For a the period of time from the final pre-operative visit until 7 days after surgical hemostasis is achieved ]Threshold is a platelet count of 50 x 10^9/L for minor surgery and 100 x 10^9/L for major surgery.
- Time to treatment failure [ Time Frame: During the period from the final pre-operative visit until 7 days after surgical hemostasis is achieved ]Time to the occurrence of a platelet count level below the designated threshold, or the administration of rescue treatment
- Surgical delays or cancellations [ Time Frame: Measured at time of planned surgery ]Proportion of patients with surgical delays or cancellations
- Bleeding [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]Graded as per the ITP bleeding score
- Thrombocytosis [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]Platelet count >400 x 10^9/L
- Blood product transfusions [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]Proportion of patients requiring platelet, red blood cells and plasma transfusions
- Rescue treatment [ Time Frame: During the period from the final pre-operative visit until 7 days after surgical hemostasis is achieved ]New ITP treatment (typically platelet transfusions, high dose IVIG or high dose corticosteroids) or an increased dose of existing ITP treatment administered to increase platelet counts above threshold
- Platelet count change over time [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]Trend of all platelet count measurements in the trial
- Patient satisfaction with treatment [ Time Frame: Immediately before surgery (final pre-op visit) and 7 days (+/- 2 days) after surgical hemostasis is achieved ]Assessed using the Treatment Satisfaction Questionnaire for Medications Score vII (which incorporates effectiveness, convenience, side effects, and overall satisfaction)
- Hospitalizations [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]Unanticipated admissions to hospital or prolongation of hospitalization
- Thrombosis [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]Symptomatic thrombotic events confirmed with diagnostic imaging
- Adverse Events [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]Defined using the Common Terminology Criteria for Adverse Events v3.0
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Primary or secondary ITP;
- Platelet count below surgical platelet count threshold (50 x10^9/L for minor surgery; 100 x 10^9/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) or no ITP medication for at least 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;
- AST, ALT above 2X upper limit of normal;
- Bilirubin above 1.5X upper limit of normal in the absence of clinically benign liver disorder (eg. Gilberts syndrome);
- 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.
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 76305 | arnold@mcmaster.ca | |
| Contact: Julie B Carruthers, MLT | 905-525-9140 ext 22942 | carrutj@mcmaster.ca |
| Canada, Alberta | |
| University of Alberta Hospital | Recruiting |
| Edmonton, Alberta, Canada, T6G2G3 | |
| Contact: Loree Larratt, MD 780-407-7021 llarratt@ualberta.ca | |
| Contact: Ovais Shaikh 780-407-6090 Ovais.Shaikh@albertahealthservices.ca | |
| Principal Investigator: Loree Laratt, MD | |
| Sub-Investigator: Irwindeep Sandhu, MD | |
| Canada, British Columbia | |
| Vancouver General Hospital | Terminated |
| Vancouver, British Columbia, Canada, V5Z1M9 | |
| Canada, Ontario | |
| Hamilton Health Sciences | Recruiting |
| Hamilton, Ontario, Canada, L8N 3Z5 | |
| Contact: Donald M Arnold, MD 905-525-9140 ext 28603 arnold@mcmaster.ca | |
| Contact: Erin Jamula, MSc 905-525-9140 ext 21845 jamulae@mcmaster.ca | |
| Principal Investigator: Donald M Arnold, MD | |
| London Health Sciences Center | Recruiting |
| London, Ontario, Canada, N6A5W9 | |
| Contact: Cyrus Hsia, MD 519-685-8500 ext 56060 cyrus.hsia@lhsc.on.ca | |
| Contact: Maisam Abouzeenni Maisam.Abouzeenni@lhsc.on.ca | |
| Principal Investigator: Cyrus Hsia, MD | |
| Ottawa Hospital | Recruiting |
| Ottawa, Ontario, Canada, K1H8L6 | |
| Contact: Alan Tinmouth, MD 613-737-8899 ext 73914 Atinmouth@toh.ca | |
| Contact: Holly Carr hcarr@ohri.ca | |
| Principal Investigator: Alan Tinmouth, MD | |
| Sunnybrook Hospital | Recruiting |
| Toronto, Ontario, Canada, M4N3M5 | |
| Contact: Yulia Lin, MD 416-480-6100 ext 2781 Yulia.Lin@sunnybrook.ca | |
| Principal Investigator: Yulia Lin, MD | |
| St.Micheal's Hospital | Recruiting |
| 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 | |
| Canada, Quebec | |
| Hopital Maisonneuve-Rosemont | Recruiting |
| Montreal, Quebec, Canada, H1T2M4 | |
| Contact: Jeannine Kassis, MD 514-252-3404 jkassis.hmr@ssss.gouv.qc.ca | |
| Contact: Julie Trinh Lu, B.Sc, DESS 514-252-3400 ext 3336 jtlu.hmr@ssss.gouv.qc.ca | |
| Principal Investigator: Jeannine Kassis, MD | |
| Jewish General Hospital | Recruiting |
| Montreal, Quebec, Canada, H3T1E2 | |
| Contact: Mark Blostein, MD 514-340-8214 mark.blostein@mgill.ca | |
| Contact: Vivian Pananis 514-340-8222 ext 5982 vpananis@gmail.com | |
| Principal Investigator: Mark Blostein, MD | |
| Principal Investigator: | Donald M Arnold, MD MSc | McMaster University |
| Responsible Party: | Donald Arnold, Principal Investigator, McMaster University |
| ClinicalTrials.gov Identifier: | NCT01621204 History of Changes |
| Other Study ID Numbers: |
M-EIBS-A-12 |
| First Posted: | June 18, 2012 Key Record Dates |
| Last Update Posted: | June 18, 2018 |
| Last Verified: | June 2018 |
Keywords provided by Donald Arnold, McMaster University:
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Thrombocytopenia ITP Platelets Bleeding |
Immune Eltrombopag IVIG |
Additional relevant MeSH terms:
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Blood Platelet Disorders Thrombocytopenia Purpura Purpura, Thrombocytopenic Purpura, Thrombocytopenic, Idiopathic Hematologic Diseases Blood Coagulation Disorders Hemorrhage Pathologic Processes Skin Manifestations Signs and Symptoms |
Thrombotic Microangiopathies Immune System Diseases Hemorrhagic Disorders Autoimmune Diseases Immunoglobulins Antibodies Immunoglobulins, Intravenous gamma-Globulins Rho(D) Immune Globulin Immunologic Factors Physiological Effects of Drugs |