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

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

Sponsors

Lead sponsor: McMaster University

Collaborator: GlaxoSmithKline
Hamilton Health Sciences Corporation
Novartis

Source McMaster University
Brief Summary

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.

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).

Overall Status Completed
Start Date October 2012
Completion Date August 2019
Primary Completion Date June 2019
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
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 For a the period of time from the final pre-operative visit until 7 days after surgical hemostasis is achieved
Secondary Outcome
Measure Time Frame
Time to treatment failure During the period from the final pre-operative visit until 7 days after surgical hemostasis is achieved
Surgical delays or cancellations Measured at time of planned surgery
Bleeding During treatment and follow up (on average, 8 weeks from starting treatment)
Thrombocytosis During treatment and follow up (on average, 8 weeks from starting treatment)
Blood product transfusions During treatment and follow up (on average, 8 weeks from starting treatment)
Rescue treatment During the period from the final pre-operative visit until 7 days after surgical hemostasis is achieved
Platelet count change over time During treatment and follow up (on average, 8 weeks from starting treatment)
Patient satisfaction with treatment Immediately before surgery (final pre-op visit) and 7 days (+/- 2 days) after surgical hemostasis is achieved
Hospitalizations During treatment and follow up (on average, 8 weeks from starting treatment)
Thrombosis During treatment and follow up (on average, 8 weeks from starting treatment)
Adverse Events During treatment and follow up (on average, 8 weeks from starting treatment)
Enrollment 74
Condition
Intervention

Intervention type: Drug

Intervention name: Eltrombopag

Description: 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).

Arm group label: Eltrombopag

Other name: Revolade

Intervention type: Drug

Intervention name: IVIG infusion

Description: 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

Arm group label: IVIG infusion

Eligibility

Criteria:

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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Donald M Arnold, MD MSc Principal Investigator McMaster University
Location
facility
University of Alberta Hospital | Edmonton, Alberta, T6G2G3, Canada
Vancouver General Hospital | Vancouver, British Columbia, V5Z1M9, Canada
Hamilton Health Sciences | Hamilton, Ontario, L8N 3Z5, Canada
London Health Sciences Center | London, Ontario, N6A5W9, Canada
Ottawa Hospital | Ottawa, Ontario, K1H8L6, Canada
Sunnybrook Hospital | Toronto, Ontario, M4N3M5, Canada
St.Micheal's Hospital | Toronto, Ontario, M5B1W8, Canada
Hopital Maisonneuve-Rosemont | Montreal, Quebec, H1T2M4, Canada
Jewish General Hospital | Montreal, Quebec, H3T1E2, Canada
The Haga Hospital | The Hague, Netherlands
Location Countries

Canada

Netherlands

Verification Date

February 2020

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: McMaster University

Investigator full name: Donald Arnold

Investigator title: Principal Investigator

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Eltrombopag

Arm group type: Experimental

Description: 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.

Arm group label: IVIG infusion

Arm group type: Active Comparator

Description: 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.

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Supportive Care

Masking: None (Open Label)

Source: ClinicalTrials.gov