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

NCT01621204 | Completed Phase 3 DMC

• 1 other identifier: M-EIBS-A-12
• Study Type: interventional
• Target: 74
• Locations: 2 countries
• Sites: 10

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.

Conditions

Immune Thrombocytopenic Purpura

Keywords

Thrombocytopenia; ITP; Platelets; Bleeding; Immune; Eltrombopag; IVIG

Outcome Measures

Primary Outcomes (1)

• 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

  Threshold is a platelet count of 50 x 10\^9/L for minor surgery and 100 x 10\^9/L for major surgery.

  For a the period of time from the final pre-operative visit until 7 days after surgical hemostasis is achieved

Secondary Outcomes (11)

• 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)

Study Arms (2)

Eltrombopag

EXPERIMENTAL

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.

Drug: Eltrombopag

IVIG infusion

ACTIVE COMPARATOR

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

Interventions

Eltrombopag 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).

Also known as: Revolade

Eltrombopag

IVIG infusion 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

Also known as: Intravenous Immunoglobulin, IgG

IVIG infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• McMaster University: lead
• GlaxoSmithKline: collaborator
• Hamilton Health Sciences Corporation: collaborator
• Novartis: collaborator

Study Sites (10)

University of Alberta Hospital

Edmonton, Alberta, T6G2G3, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z1M9, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

London Health Sciences Center

London, Ontario, N6A5W9, Canada

Location

Ottawa Hospital

Ottawa, Ontario, K1H8L6, Canada

Location

Sunnybrook Hospital

Toronto, Ontario, M4N3M5, Canada

Location

St.Micheal's Hospital

Toronto, Ontario, M5B1W8, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T2M4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

The Haga Hospital

The Hague, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 32853584 RESULT

• 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.

  PMID: 30685874 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Hemorrhage

Interventions

eltrombopag; Immunoglobulins, Intravenous; Immunoglobulin G

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Donald M Arnold, MD MSc

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 12, 2012
• First Posted: June 18, 2012
• Study Start: October 1, 2012
• Primary Completion: June 1, 2019
• Study Completion: August 1, 2019
• Last Updated: September 9, 2020

Record last verified: 2020-09

Locations

NL (1); CA (9)