Eltrombopag Plus Diacerein vs Eltrombopag in Adult ITP

NCT04917679 | Completed Phase 2 DMC

• 1 other identifier: Eltrombopag-Diacerein ITP
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

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.

Conditions

Thrombocytopenia

Keywords

ITP; Eltrombopag; Diacerein

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 15

Secondary Outcomes (6)

• Response at Day 28

  Day 28

• Time to response

  28 days

• Duration of response

  12 months

• Bleeding scores

  12 months

• Health-related quality of life assessment

  12 weeks

Study Arms (2)

Combination group

EXPERIMENTAL

Eltrombopag plus diacerein

Drug: Eltrombopag plus diacerein

Monotherapy group

PLACEBO COMPARATOR

Eltrombopag monotherapy

Drug: Eltrombopag

Interventions

Eltrombopag plus diacerein DRUG

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.

Combination group

Eltrombopag DRUG

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.

Monotherapy group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead

Study Sites (1)

Qilu hospital, Shandong University

Jinan, Shandong, China

Location

Related Publications (3)

• 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.

  PMID: 19846889 BACKGROUND

• 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.

  PMID: 19005182 BACKGROUND

• Sun L, Huang X, Wang J, Yuan C, Zhao H, Li D, Xu R, Wang Y, Qin P, Shi Y, Peng J, Hou M, Hou Y. Eltrombopag plus diacerein vs eltrombopag in patients with ITP: a multicenter, randomized, open-label phase 2 trial. Blood. 2024 Oct 24;144(17):1791-1799. doi: 10.1182/blood.2024025067.

  PMID: 38958479 DERIVED

MeSH Terms

Conditions

Thrombocytopenia

Interventions

eltrombopag; diacerein

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Study Officials

• Yu Hou

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: June 8, 2021
• Study Start: September 1, 2020
• Primary Completion: December 1, 2021
• Study Completion: June 1, 2022
• Last Updated: October 19, 2023

Record last verified: 2023-06

Locations

CN (1)