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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2012 by McMaster University
Sponsor:
Collaborators:
GlaxoSmithKline
Hamilton Health Sciences Corporation
Information provided by (Responsible Party):
Donald Arnold, McMaster University
ClinicalTrials.gov Identifier:
NCT01621204
First received: June 12, 2012
Last updated: June 15, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Immune Thrombocytopenic Purpura
Drug: Eltrombopag
Drug: IVIG infusion
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (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

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    Hemostasis will be assessed daily after surgery. The main outcome measure (platelet count above threshold) will be evaluated 7 days after hemostasis is acheived.


Secondary Outcome Measures:
  • Time to treatment failure [ Time Frame: During the period from surgery until 7 days after surgical hemostasis is acehieved ] [ Designated as safety issue: No ]
  • Bleeding [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ] [ Designated as safety issue: Yes ]
  • Proportion of participants who undergo surgery as planned [ Time Frame: Measured at time of planned surgery (2 week for IVIG; 3 weeks for eltrombopag) ] [ Designated as safety issue: No ]
  • Treatment satisfaction assessment [ Time Frame: Assessed immediately before surgery (Day -2) and at 4 weeks (average for IVIG) or 5 weeks (average for eltrombopag). ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    Rare known adverse event with eltrombopag

  • Adverse Events [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 74
Study Start Date: July 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Eltrombopag
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.
Other Names:
  • Intervenous Immunoglobulin
  • IgG

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Primary or secondary ITP;
  • Platelet count below surgical platelet count threshold (50 x10exp9/L for minor surgery; 100 x 10exp9/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),excluding IVIG and thrombopoietin receptor agonists, or no ITP medication in the past 4 weeks;
  • Surgery date is at least 3 weeks after screening date;
  • 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;
  • Known previous IVIG treatment failure (defined as the lack of a platelet count doubling from baseline and increase above 50 x10exp9/L by 2 weeks);
  • Known previous thrombopoietin receptor agonist treatment failure (defined as the lack of a platelet count doubling from baseline and increase above 50 x10exp9/L by 2 weeks)
  • AST, ALT above 2X upper limit of normal;
  • Bilirubin above 1.5X upper limit of normal;
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01621204

Contacts
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

Locations
Canada, Ontario
Hamilton Health Sciences Not yet recruiting
Hamilton, Ontario, Canada, L8N 3Z5
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   
Principal Investigator: Donald M Arnold, MD         
Sponsors and Collaborators
McMaster University
GlaxoSmithKline
Hamilton Health Sciences Corporation
Investigators
Principal Investigator: Donald M Arnold, MD MSc McMaster University
  More Information

No publications provided

Responsible Party: Donald Arnold, Principal Investigator, McMaster University
ClinicalTrials.gov Identifier: NCT01621204     History of Changes
Other Study ID Numbers: M-EIBS-A-12
Study First Received: June 12, 2012
Last Updated: June 15, 2012
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
Thrombocytopenia
ITP
Platelets
Bleeding
Immune
Eltrombopag
IVIG

Additional relevant MeSH terms:
Blood Platelet Disorders
Purpura
Purpura, Thrombocytopenic
Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases
Antibodies
Immunoglobulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014