A Multicenter Randomized Open-label Study of Chidamide Plus HD-DEX Versus HD-DEX in ITP

Sponsor
Shandong University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05411874
Collaborator
(none)
100
2
25

Study Details

Study Description

Brief Summary

Recently, histone deacetylase inhibitors (HDACi) has been used for their anti-inflammatory and immunomodulatory activities. It has been shown that HDACi can alleviate graft-versus-host disease by enhancing the number and function of Foxp3+ Tregs. Our group found that low-dose HDACi alleviated thrombocytopenia in both passive and active murine models of ITP. Furthermore, low-dose HDACi attenuated macrophage phagocytosis of antibody-coated platelets, stimulated production of natural Foxp3+ Tregs, promoted peripheral conversion of T cells into Tregs, and restored Treg suppressive function in vivo and in vitro. The project was undertaking by Qilu Hospital of Shandong University and other 10 well-known hospitals in China. In order to report the efficacy and safety of the low dose chidamide combined with high-dose dexamethasone versus high-dose dexamethasone in the management of ITP.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with low platelet count. Low-dose HDACi alleviated thrombocytopenia in both passive and active murine models of ITP. In this multicentre, open-label, randomized controlled trial, newly diagnosed ITP patients will be enrolled from 11 tertiary medical centres in China. Participants will be randomly assigned into the combination group or the monotherapy group by masked statisticians in a 1:1 ratio. The primary endpoints are sustained response at month 6. The secondary outcomes include initial response, 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 low dose chidamide combined with high-dose dexamethasone versus high-dose dexamethasone monotherapy in adults with primary immune thrombocytopenia.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter Randomized Open-label Study of Chidamide Combined With High-dose Dexamethasone Versus High-dose Dexamethasone in the Management of Newly-Diagnosed Immune Thrombocytopenia
Anticipated Study Start Date :
Oct 1, 2022
Anticipated Primary Completion Date :
Oct 30, 2023
Anticipated Study Completion Date :
Oct 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Chidamide plus HD-DXM

Chidamide (orally at 5 mg biw for 24 weeks) HD-DXM (orally at 40 mg daily for 4 days)

Drug: Chidamide
5mg po biw for 24 weeks

Drug: HD-DXM
40mg po qd for 4days

Active Comparator: HD-DXM

HD-DXM (orally at 40 mg daily for 4 days )

Drug: HD-DXM
40mg po qd for 4days

Outcome Measures

Primary Outcome Measures

  1. Sustained response [6 month]

    The maintenance of platelet count ≥ 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 6-month follow-up.

Secondary Outcome Measures

  1. Initial response [day 14]

    CR: platelet count ≥ 100 × 109/L and absence of bleeding; R: platelet count ≥ 30 × 109/L but < 100 × 109/L and a doubling from baseline and absence of bleeding.

  2. Number of patients with bleeding [6 month]

    Number of patients with bleeding complication. 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. Scores ranged from 0 to 59, with higher values indicating higher bleeding risk.

  3. Number of patients with adverse events [6 month]

    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.

  4. Time to response [6 month]

    The time from starting treatment to time of achievement of CR or R

  5. Duration of response (DOR) [6 month]

    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).

  6. Health-related quality of life assessment [6 month]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • newly diagnosed ITP patients need of treatment(s) to minimize the risk of clinically significant bleeding primary ITP confirmed by excluding other supervened causes of thrombocytopenia
Exclusion Criteria:
  • pregnancy hypertension cardiovascular disease diabetes liver and kidney function impairment HCV, HIV, HBsAg seropositive status patients with systemic lupus erythematosus and/or antiphospholipid syndrome

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Shandong University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Ming Hou, Professor and Director, Shandong University
ClinicalTrials.gov Identifier:
NCT05411874
Other Study ID Numbers:
  • ITP-Chidamide plus DEX
First Posted:
Jun 9, 2022
Last Update Posted:
Jun 9, 2022
Last Verified:
Jun 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Ming Hou, Professor and Director, Shandong University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 9, 2022