The Combination of ATRA and High-dose Dexamethasone as First-line Treatment in Adult Immune Thrombocytopenia

The Combination of Oral All-trans Retinoic Acid and High-dose Dexamethasone vs High-dose Dexamethasone as First-line Treatment in Adult Immune Thrombocytopenia: A Multicenter, Randomized, Open-label Trial

Randomized, open-label, multicenter study to compare the efficacy and safety of ATRA plus high-dose dexamethasone compared to high-dose dexamethasone monotherapy for the first-line treatment of adults with primary immune thrombocytopenia (ITP).

Study Overview

• Status: Completed
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Dexamethasone; Drug: ATRA

Detailed Description

The investigators are undertaking a parallel group, multicenter, randomized controlled trial of 132 adults with ITP in China. Patients were randomized to ATRA+ high-dose dexamethasone and high-dose dexamethasone monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University Insititute of Hematology, Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Confirmed newly-diagnosed, treatment-naive ITP;
2. Platelet counts <30×109/L ;
3. Platelet counts < 50×109/L and significant bleeding symptoms (WHO bleeding scale 2 or above);
4. Willing and able to sign written informed consent.

Exclusion Criteria:

1. Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit;
2. Received first-line and second-line ITP-specific treatments (eg, steriods, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, etc) ;
3. Current HIV infection or hepatitis B virus or hepatitis C virus infections;
4. Active infection;
5. Maligancy;
6. Severe medical condition (lung, hepatic or renal disorder) other than chronic ITP. Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia);
7. Female patients who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period; a history of clinically significant adverse reactions to previous corticosteroid therapy
8. Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test;
9. Patients who are deemed unsuitable for the study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ATRA and HD-DXM; Dexamethasone 40 mg per day, 4 consecutive days (the 4-day course of dexamethasone was repeated in the case of lack of response by day 10) and ATRA 10mg bid po, 12 consecutive weeks	Drug: Dexamethasone; Dexamethasone, iv, 40 mg/d, for 4 days (The 4-day course of dexamethasone was repeated in the case of lack of response by day 10); Other Names: HD-DXM; High-dose Dexamethasone; Drug: ATRA; ATRA, po,10mg bid, for 12 weeks; Other Names: All-trans retinoic acid
ACTIVE_COMPARATOR: HD-DXM; Dexamethasone 40 mg per day, 4 consecutive days (the 4-day course of dexamethasone was repeated in the case of lack of response by day 10)	Drug: Dexamethasone; Dexamethasone, iv, 40 mg/d, for 4 days (The 4-day course of dexamethasone was repeated in the case of lack of response by day 10); Other Names: HD-DXM; High-dose Dexamethasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained response	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.	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete response (CR)	complete response (CR) was defined as platelet count more than 100,000 per cubic millimeter and absence of bleeding.	day 14
Response (R)	Response (R) as platelet count more than 30,000 per cubic millimeter and at least 2-fold increase of the baseline count and absence of bleeding.	day 14
Time to response	The time from starting treatment to time of achievement of CR or R	6 month
Number of patients with bleeding	Number of patients with bleeding complication ( WHO bleeding score).	6 month
Number of patients with adverse events	Number of patients with adverse events.	6 month
Duration of response (DOR)	Duration of response at 6-month follow up.	6 month
Loss of response	Platelet counts below 100 x 109/L or bleeding (from CR) or platelet counts below 30 x 109/L, less than 2-fold increase of baseline platelet count or bleeding (from R)	6 month

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Qilu Hospital of Shandong University; Beijing Tongren Hospital; Beijing Hospital; Navy General Hospital, Beijing; Beijing Aerospace General Hospital

Publications and helpful links

General Publications

• Huang QS, Liu Y, Wang JB, Peng J, Hou M, Liu H, Feng R, Wang JW, Xu LP, Wang Y, Huang XJ, Zhang XH. All-trans retinoic acid plus high-dose dexamethasone as first-line treatment for patients with newly diagnosed immune thrombocytopenia: a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Haematol. 2021 Oct;8(10):e688-e699. doi: 10.1016/S2352-3026(21)00240-4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2020
• Primary Completion (ACTUAL): June 30, 2020
• Study Completion (ACTUAL): June 30, 2020

Study Registration Dates

• First Submitted: December 30, 2019
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (ACTUAL): January 3, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dermatologic Agents; Keratolytic Agents; Dexamethasone; Dexamethasone acetate; BB 1101; Tretinoin
• Other Study ID Numbers: ITP-PKU007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to data, including deidentified individual participant data, and the study protocol from this clinical trial. These data will be available beginning 3 months and ending 36 months following publication. All requests must include a description of the research proposal and be sent to the corresponding author (zhangxh@bjmu.edu.cn). Data requestors will need to sign a data access agreement to obtain access.
• IPD Sharing Time Frame: These data will be available beginning 3 months and ending 36 months following publication.
• IPD Sharing Access Criteria: All requests must include a description of the research proposal and be sent to the corresponding author (zhangxh@bjmu.edu.cn). Data requestors will need to sign a data access agreement to obtain access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No