Back to resultsEltrombopag Plus Diacerein vs Eltrombopag in Adult ITP
Primary Purpose
Thrombocytopenia
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Eltrombopag plus diacerein
Eltrombopag
Sponsored by
About this trial
This is an interventional treatment trial for Thrombocytopenia focused on measuring ITP, Eltrombopag, Diacerein
Eligibility Criteria
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.
Sites / Locations
- Qilu hospital, Shandong University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Combination group
Monotherapy group
Arm Description
Eltrombopag plus diacerein
Eltrombopag monotherapy
Outcomes
Primary Outcome Measures
Initial response at 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.
Secondary Outcome Measures
Response at 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.
Time to response
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.
Duration of response
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).
Bleeding scores
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.
Health-related quality of life assessment
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.
The number of participants with Adverse events
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.
Full Information
NCT ID
NCT04917679
First Posted
December 1, 2020
Last Updated
October 17, 2023
Sponsor
Qilu Hospital of Shandong University
1. Study Identification
Unique Protocol Identification Number
NCT04917679
Brief Title
Eltrombopag Plus Diacerein vs Eltrombopag in Adult ITP
Official Title
Eltrombopag Plus Diacerein vs Eltrombopag in Adult Primary Immune Thrombocytopenia: a Multicenter Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
December 1, 2021 (Actual)
Study Completion Date
June 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Qilu Hospital of Shandong University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombocytopenia
Keywords
ITP, Eltrombopag, Diacerein
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Combination group
Arm Type
Experimental
Arm Description
Eltrombopag plus diacerein
Arm Title
Monotherapy group
Arm Type
Placebo Comparator
Arm Description
Eltrombopag monotherapy
Intervention Type
Drug
Intervention Name(s)
Eltrombopag plus diacerein
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Eltrombopag
Intervention Description
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.
Primary Outcome Measure Information:
Title
Initial response at Day 15
Description
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.
Time Frame
Day 15
Secondary Outcome Measure Information:
Title
Response at Day 28
Description
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.
Time Frame
Day 28
Title
Time to response
Description
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.
Time Frame
28 days
Title
Duration of response
Description
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).
Time Frame
12 months
Title
Bleeding scores
Description
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.
Time Frame
12 months
Title
Health-related quality of life assessment
Description
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.
Time Frame
12 weeks
Title
The number of participants with Adverse events
Description
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.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yu Hou
Organizational Affiliation
Qilu Hospital, Shandong University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Qilu hospital, Shandong University
City
Jinan
State/Province
Shandong
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
19846889
Citation
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.
Results Reference
background
PubMed Identifier
19005182
Citation
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.
Results Reference
background
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Eltrombopag Plus Diacerein vs Eltrombopag in Adult ITP
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