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

NCT ID: NCT01621204

Last Updated: 2020-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2019-08-31

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).

Conditions

Immune Thrombocytopenic Purpura

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Eltrombopag

Intervention Type: DRUG

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).

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.

Group Type: ACTIVE_COMPARATOR

IVIG infusion

Intervention Type: DRUG

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

Interventions

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).

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Revolade; Intravenous Immunoglobulin; IgG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Donald Arnold

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Donald M Arnold, MD MSc

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

University of Alberta Hospital

Edmonton, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Hamilton Health Sciences

Hamilton, Ontario, Canada

London Health Sciences Center

London, Ontario, Canada

Ottawa Hospital

Ottawa, Ontario, Canada

Sunnybrook Hospital

Toronto, Ontario, Canada

St.Micheal's Hospital

Toronto, Ontario, Canada

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Jewish General Hospital

Montreal, Quebec, Canada

The Haga Hospital

The Hague, , Netherlands

Countries

Canada; Netherlands

References

Arnold DM, Heddle NM, Cook RJ, Hsia C, Blostein M, Jamula E, Sholzberg M, Lin Y, Kassis J, Larratt L, Tinmouth A, Amini S, Schipperus M, Lim W, Vishnu P, Warner M, Carruthers J, Li N, Lane S, Kelton JG. Perioperative oral eltrombopag versus intravenous immunoglobulin in patients with immune thrombocytopenia: a non-inferiority, multicentre, randomised trial. Lancet Haematol. 2020 Sep;7(9):e640-e648. doi: 10.1016/S2352-3026(20)30227-1.

Reference Type: RESULT

PMID: 32853584 (View on PubMed)

Arnold DM, Jamula E, Heddle NM, Cook RJ, Hsia C, Sholzberg M, Lin Y, Kassis J, Blostein M, Larratt L, Amini S, Schipperus M, Carruthers J, Lane SJ, Li N, Kelton JG. Peri-Operative Eltrombopag or Immune Globulin for Patients with Immune Thrombocytopaenia (The Bridging ITP Trial): Methods and Rationale. Thromb Haemost. 2019 Mar;119(3):500-507. doi: 10.1055/s-0038-1677531. Epub 2019 Jan 27.

Reference Type: DERIVED

PMID: 30685874 (View on PubMed)

Other Identifiers

M-EIBS-A-12

Identifier Type: -

Identifier Source: org_study_id