- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04917679
Eltrombopag Plus Diacerein vs Eltrombopag in Adult ITP
October 17, 2023 updated by: Qilu Hospital of Shandong University
Eltrombopag Plus Diacerein vs Eltrombopag in Adult Primary Immune Thrombocytopenia: a Multicenter Randomized Controlled Trial
Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with low platelet count.
As the first choice of the second-line treatment of ITP, thrombopoietin receptor agonist (TPO-RA) enable long-term remission in 50% to 60% of cases.
However, about half of patients have no response or loss of response to eltrombopag due to unknown reasons, which can't be effectively improved by increasing the drug dose.
Diacerein is an anthraquinone derivative used to treat joint diseases such as osteoarthritis.
We speculate that the addition of diacerein to eltrombopag may offer sensitizer effect and maximize efficacy, which warrants further prospective studies to evaluate the efficacy and safety of the combination therapy as salvage strategy in ameliorating immune thrombocytopenia.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
In this multicentre, open-label, randomized controlled trial, 98 eltrombopag-inefficient or relapsed ITP patients will be enrolled from five tertiary medical centres in China.
Participants will be randomly assigned into the combination group (eltrombopag orally at initial dose of 75 mg daily for 14 days, plus diacerein orally at initial dose of 50 mg bid for 14 days) or the monotherapy group (eltrombopag orally at initial dose of 75 mg daily for 14 days) by masked statisticians in a 1:1 ratio.
The primary endpoints are initial response at D15 without any additional ITP-specific intervention.
The secondary outcomes include response at D28, time to response, duration of response, bleeding score, health-related quality of life assessment, and safety issue.
This study will compare the efficacy and safety of eltrombopag-diacerein with eltrombopag monotherapy in adults with primary immune thrombocytopenia.
We hypothesized that the novel combination of eltrombopag and diacerein might extend eltrombopag efficacy and avoid rapid alteration to less-preferable therapies, especially in the management of the patient refractory to eltrombopag.
Study Type
Interventional
Enrollment (Actual)
102
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Shandong
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Jinan, Shandong, China
- Qilu Hospital, Shandong University
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Participant must be at least 18 years of age at the time of the screening.
- Participant may be male or female.
- Participant has a confirmed diagnosis of ITP according to the 2019 International Working Group assessment at screening.
- Participant who didn't respond to eltrombopag retreatment (75mg by mouth once a day for 14 days) after eltrombopag previous treatment inefficient or relapsed (platelet count below 30 × 10^9/L or below 2-fold increase from baseline platelet count, or bleeding).
- Bone marrow biopsy is performed in participants over 60 years to exclude hematological malignancies.
Exclusion Criteria:
- Participant has evidence of a secondary cause of immune thrombocytopenia (e.g. leukemia, lymphoma, common variable immune-deficiency, systemic lupus erythematosus, autoimmune thyroid disease, past medical history of untreated H. pylori infection) or to drug treatments (e.g. heparin, quinine, antimicrobials, anticonvulsants) or participant has a multiple immune cytopenia, e.g. Evan's syndrome.
- Participant has clinically life-threatening bleeding (e.g. central nervous system bleeding, menorrhagia with significant drop in hemoglobin). Participant has a history of coagulopathy disorders other than ITP.
- Participant has a history of arterial or venous thromboembolism (e.g. stroke, transient ischemic attach, myocardial infarction, deep vein thrombosis or pulmonary embolism) within the 6 months prior to randomization or requires anticoagulant treatment.
- Participant has 12-lead ECG with changes considered to be clinically significant upon medical review at baseline.
- Participant has severe renal impairment (glomerular filtration rate less than 45ml/min/1.73 m2).
- Participant has 3 × upper limit of normal of any of the following: alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase.
- Participant has received corticosteroids, rh-TPO, romiplostim, or immunosuppression within 4 weeks before screening.
- Participant with any of the following conditions: severe immunodeficiency, active or previous malignancy, human immunodeficiency virus (HIV), hepatitis B or C virus infection, pregnancy or lactation.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Combination group
Eltrombopag plus diacerein
|
In the combination group, eltrombopag will be administered orally at an initial dose of 75mg daily for 14 days, and diacerein will be given orally at an initial dose of 50mg bid concomitantly for 14 days (D1-D14).
During treatment period, treating physicians will modify the dosage of trial treatment to maintain participants' platelet count at the range of 50 - 150 × 10^9/L as follows: (1) if platelet count is less than 150 × 10^9/L, continue the original treatment (eltrombopag 75mg daily plus diacerein 50mg bid); (2) if platelet count is between 150 × 10^9/L to 250 × 10^9/L, the treatment will be modified to eltrombopag 50mg daily plus diacerein 50mg bid; (3) if platelet count is over 250 × 10^9/L, original treatment (both eltrombopag and diacerein) need to be stopped, and platelet count should be reexamined every other day, and the treatment (eltrombopag 50mg daily plus diacerein 50mg bid ) will be restarted until platelet count is below 100 × 10^9/L.
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Placebo Comparator: Monotherapy group
Eltrombopag monotherapy
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In the monotherapy group, eltrombopag also will be administered orally at an initial dose of 75mg daily for 14 days (D1-D14), and the individualized dosage could be modified by treating physicians to maintain participants' platelet count between 50 × 10^9/L to 150 × 10^9/L.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Initial response at Day 15
Time Frame: Day 15
|
The primary outcomes of this trial are initial responses at Day 15 without any additional ITP-specific intervention.
Complete response was defined as a platelet count at or above 100 × 10⁹ cells per L and an absence of bleeding.
Partial response was defined as a platelet count at or above 30 × 10⁹ cells per L but less than 100 × 10⁹ cells per L and at least a doubling of the baseline platelet count and an absence of bleeding.
No response was defined as a platelet count of less than 30 × 10⁹ cells per L, or less than two-times increase from baseline platelet count, or bleeding.
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Day 15
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response at Day 28
Time Frame: Day 28
|
Responses were assessed at day 28.
Complete response was defined as a platelet count at or above 100 × 10⁹ cells per L and an absence of bleeding.
Partial response was defined as a platelet count at or above 30 × 10⁹ cells per L but less than 100 × 10⁹ cells per L and at least a doubling of the baseline platelet count and an absence of bleeding.
No response was defined as a platelet count of less than 30 × 10⁹ cells per L, or less than two-times increase from baseline platelet count, or bleeding.
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Day 28
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Time to response
Time Frame: 28 days
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Time to response was defined as the time from treatment initiation to achieve a complete response or a partial response, whichever came first, assessed up to day 28.
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28 days
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Duration of response
Time Frame: 12 months
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Duration of response was defined as the time from achievement of a complete response or a partial response to the loss of response (platelet count <30 × 10⁹ cells per L; measured on two occasions more than 1 day apart or the presence of bleeding).
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12 months
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Bleeding scores
Time Frame: 12 months
|
Bleeding symptoms were graded according a standardized bleeding scale specific to primary immune thrombocytopenia on the basis of site and severity of bleeding by Khellaf et al (PMID: 15951296).
A modification was made to exclude age from the original scale so that only bleeding symptoms were described.
At each visit, we recorded bleeding scores.
Routine visits were scheduled once a week for the first 4 weeks and once a month thereafter.
Scores ranged from 0 to 59, with higher values indicating higher bleeding risk.
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12 months
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Health-related quality of life assessment
Time Frame: 12 weeks
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Health-related quality of life was assessed using a self-administered immune thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) at baseline and at week 12. Scores ranged from 0 to 100, with higher values indicating better quality of life.
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12 weeks
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The number of participants with Adverse events
Time Frame: 12 months
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Adverse events were graded according to the Common Terminology Criteria for Adverse Events (version 4.0).
At each visit, we recorded adverse events.
Routine visits were scheduled once a week for the first 4 weeks and once a month thereafter.
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12 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Yu Hou, Qilu Hospital, Shandong University
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010 Jan 14;115(2):168-86. doi: 10.1182/blood-2009-06-225565. Epub 2009 Oct 21.
- Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 1, 2020
Primary Completion (Actual)
December 1, 2021
Study Completion (Actual)
June 1, 2022
Study Registration Dates
First Submitted
December 1, 2020
First Submitted That Met QC Criteria
June 1, 2021
First Posted (Actual)
June 8, 2021
Study Record Updates
Last Update Posted (Actual)
October 19, 2023
Last Update Submitted That Met QC Criteria
October 17, 2023
Last Verified
June 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Eltrombopag-Diacerein ITP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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