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

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ClinicalTrials.gov Identifier: NCT01621204
Recruitment Status : Recruiting
First Posted : June 18, 2012
Last Update Posted : June 18, 2018
Sponsor:
Collaborators:
GlaxoSmithKline
Hamilton Health Sciences Corporation
Novartis
Information provided by (Responsible Party):
Donald Arnold, McMaster University

June 12, 2012
June 18, 2012
June 18, 2018
October 2012
January 2019   (Final data collection date for primary outcome measure)
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.
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) ]
Hemostasis will be assessed daily after surgery. The main outcome measure (platelet count above threshold) will be evaluated 7 days after hemostasis is acheived.
Complete list of historical versions of study NCT01621204 on ClinicalTrials.gov Archive Site
  • 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
  • Time to treatment failure [ Time Frame: During the period from surgery until 7 days after surgical hemostasis is acehieved ]
  • Bleeding [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]
  • Proportion of participants who undergo surgery as planned [ Time Frame: Measured at time of planned surgery (2 week for IVIG; 3 weeks for eltrombopag) ]
  • Treatment satisfaction assessment [ Time Frame: Assessed immediately before surgery (Day -2) and at 4 weeks (average for IVIG) or 5 weeks (average for eltrombopag). ]
    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) ]
    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) ]
    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) ]
    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) ]
    Rare known adverse event with eltrombopag
  • Adverse Events [ Time Frame: During treatment and follow up (on average, 8 weeks from starting treatment) ]
Not Provided
Not Provided
 
A Trial of Eltrombopag or Intravenous Immune Globulin Before Surgery for Immune Thrombocytopenia Patients
Treatment of thromBocytopenia With EltRombopag or Intravenous Immune Globulin (IVIG) Before and DurING Invasive Procedures in Patients With Immune ThrombocytoPenia- BRIDGING ITP Study
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.

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).

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Immune Thrombocytopenic Purpura
  • 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
  • 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:
    • Intravenous Immunoglobulin
    • IgG
  • 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.
    Intervention: Drug: Eltrombopag
  • 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.
    Intervention: Drug: IVIG infusion
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
74
Same as current
January 2019
January 2019   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
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
 
 
NCT01621204
M-EIBS-A-12
Yes
Not Provided
Not Provided
Donald Arnold, McMaster University
McMaster University
  • GlaxoSmithKline
  • Hamilton Health Sciences Corporation
  • Novartis
Principal Investigator: Donald M Arnold, MD MSc McMaster University
McMaster University
June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP