Clinical trial NCT04917679: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thrombocytopenia
Keywords: ITP
Eltrombopag
Diacerein
Lead sponsor: Qilu Hospital of Shandong University
Sponsor class: OTHER
First posted: 2021-06-08
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Initial response at Day 15
timeFrame: Day 15
Secondary outcomes:
measure: Response at Day 28
timeFrame: Day 28
measure: Time to response
timeFrame: 28 days
measure: Duration of response
timeFrame: 12 months
measure: Bleeding scores
timeFrame: 12 months
measure: Health-related quality of life assessment
timeFrame: 12 weeks
measure: The number of participants with Adverse events
timeFrame: 12 months
Other outcomes:
Locations:
city: Jinan
country: China
facility: Qilu hospital, Shandong University
state: Shandong
Study officials:
affiliation: Qilu Hospital, Shandong University
name: Yu Hou
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.