To compare the effect of eltrombopag and IVIG on the achievement of the platelet count threshold before and after surgery.
ID
Source
Brief title
Condition
- Platelet disorders
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients achieving the platelet count threshold before surgery
and maintaining platelet counts within the
target range until 7 days after surgical hemostasis is achieved without the use
of ITP rescue treatment.
Secondary outcome
- Time to treatment failure;
- Bleeding;
- Proportion of patients who undergo surgery as planned;
- Treatment satisfaction assessed on Day -1 +/-1 day and once
during follow up using the Treatment Satisfaction
Questionnaire for Medications Score (which incorporates
effectiveness, convenience, side effects, and overall
satisfaction);
- Proportion of patients who have a platelet count greater than
400x109/L during the pre- and post-operative period;
- Use of blood transfusions (platelets, red blood cells, plasma);
- Pre-surgery platelet count levels;
- Change in pre-surgery platelet count levels from baseline;
- Proportion of post-surgery days spent below the platelet
count threshold [50x 109/L (for minor surgery); 100x 109/L (for
major surgery)] during the study period;
- Total clinic and hospital days;
- Venous thromboembolism and arterial thromboembolism;
- Adverse events.
Background summary
Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease
characterized by the presence of platelet autoantibodies, low platelet counts
and an increased risk of bleeding. The clinical presentation of ITP can range
from asymptomatic thrombocytopenia to serious hemorrhage. Many patients with
moderate to severe ITP (platelet count less than 50 x 109/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 x109/L for the vast majority
of surgical procedure; 50x109/L is a typical threshold for minor surgeries like
tooth extractions and endoscopies; and 100x109/L is used for major surgery like
cardiac surgery or neurosurgery. In preparation for this trial,we met with ITP
physicians across Canada and investigators on this trial to reach consensus
about platelet count thresholds that would be acceptable and feasible for this
ITP bridging study. Investigators agreed that thresholds of 50 x109/L for minor
surgeries and 100 x109/L for major surgeries were acceptable and reflected most
patterns of practice.
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. The use of IVIG as
bridging therapy has several disadvantages. First, it is a blood product and
thus carries a theoretical risk of infectious disease transmission. Second, it
is associated with side effects. Common side effects include headache
(approximately 10%) which can be severe and require hospitalization for 1 * 2%
of patients. Hemolysis occurs in approximately 1.6% of treated patients and is
most often an effect of high titre anti-A or anti-B in the IVIG product. Rare
thromboembolic complications of IVIG including venous (deep vein thrombosis and
pulmonary embolism) and arterial thrombosis (myocardial infarction, stroke)
have been reported in approximately 1% of treated patients. Renal failure can
occur rarely and may be related to sucrose induced osmotic nephropathy. Thus
monitoring for these complications is required particularly in elderly
patients, diabetics and patients with pre-existing renal insufficiency. Third,
IVIG is resourceintensive requiring 0.5 * 1.0 clinic days for the
administration of one intravenous dose which is often repeated, the use of
outpatient hospital services and nursing time. Finally, IVIG is expensive and
supply-limited with a high and increasing per capita cost in Canada.
Alternatives to IVIG as bridging therapy are needed.
Based on the results from Phase III studies, eltrombopag can elevate and
sustain platelet counts in a significant percentage of ITP patients receiving
continuous treatment. These studies also showed that adverse events associated
with eltrombopag therapy are uncommon compared to patients receiving placebo.
Thus, considering the cost of eltrombopag and the good safety profile, the
short-term use of eltrombopag as a bridge to surgery is appealing and may offer
a preferable alternative to IVIG for patients with ITP.
Study objective
To compare the effect of eltrombopag and IVIG on the achievement of the
platelet count threshold before and after surgery.
Study design
Randomized, open label, parallel arm, non-inferiority trial
Intervention
Eltrombopag daily oral drug for bridging to an acceptabel level of platelet
count vs. IVIG in ITP patients.
Study burden and risks
Participating subjects will have to visit the doctor more often and get 2 extra
venapunctions for control of plateletcount before and after surgery. They need
to fill a short satisfaction questionnaire twice. Patient randomized to the
eltrombopag arm will have less burden of getting IVIG, since eltrombopag is an
orally taken drug.
Group relatedness is not applicable in this study.
Els Borst-Eilersplein 275
Den Haag 2545 AA
NL
Els Borst-Eilersplein 275
Den Haag 2545 AA
NL
Listed location countries
Age
Inclusion criteria
1. Primary or secondary ITP (according to the ASH 2011 guidelines);
2. Platelet count below the surgical platelet count threshold (50 x109/L for minor surgery; 100
x 109/L for major surgery);
3. 18 years of age or older;
4. On stable doses of concomitant ITP medications (or no medication) for at least 2 weeks
(i.e. the dose administered has not changed);
5. At least 3-weeks lead time available between randomization and scheduled surgery;
6. IVIG and Eltrombopag are acceptable ITP treatment options for this patient;
7. Able to provide informed consent.
Exclusion criteria
1. Pregnancy or breastfeeding;
2. Treatment with IVIG within the last 2 weeks;
3. Treatment with a thrombopoietin receptor agonist (eltrombopag or romiplostim) within the
last 4 weeks;
4. AST, ALT above 2X upper limit of normal;
5. Bilirubin above 1.5X upper limit of normal in the absence of clinically benign liver disorder
(e.g. Gilberts syndrome);
6. Deep vein thrombosis, myocardial infarction, thrombotic stroke or arterial thrombosis in the
last 12 months;
7. History of bone marrow reticulin or fibrosis;
8. Known liver cirrhosis;
9. Active malignancy (defined as requiring treatment or palliation within the last 6 months).
10. 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.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004295-22-NL |
| ClinicalTrials.gov | NCT01621204 |
| CCMO | NL59645.098.16 |