The Combination of ATRA and Danazol as Second-line Treatment in Adult Immune Thrombocytopenia

September 3, 2017 updated by: Xiao-hui Zhang, Peking University People's Hospital

The Combination of Oral All-trans Retinoic Acid and Danazol vs Danazol as Second-line Treatment in Adult Immune Thrombocytopenia: a Multicenter, Randomized, Open-label Trial

Randomized, open-label, multicentre study to compare the efficacy and safety of ATRA plus danazol with danazol monotherapy in patients with corticosteroid-resistant/relapsed ITP.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Immune thrombocytopenia (ITP) is a severe bleeding disorder. Approximately 2/3 of patients achieve remission from first-line therapies. However, the underlying mechanism of corticosteroid-resistant or relapsed ITP is not well understood; thus, treatment remains a great challenge. All-trans retinoic acid (ATRA) has an immunomodulatory effect on haematopoiesis, making it a possible treatment option.

A multicentre prospective study was performed in non-splenectomized ITP patients who were either resistant to a standard dose of corticosteroids or had relapsed. Patients were randomized to ATRA+danazol and danazol monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study, in order to compare the efficacy and safety of ATRA plus danazol with danazol monotherapy in patients with corticosteroid-resistant/relapsed ITP.

Study Type

Interventional

Enrollment (Actual)

130

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Beijing Tongren Hospital
      • Beijing, Beijing, China, 100044
        • Beijing Hospital, Ministry of Health
      • Beijing, Beijing, China, 100044
        • Peking University People's Hospital, Peking University Insititute of Hematology
      • Beijing, Beijing, China
        • Pla Navy General Hospital
    • Shandong
      • Jinan, Shandong, China
        • Qilu Hospital, Shandong University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia;
  • Platelet count of less than 30×109/L at enrolment
  • Patients who did not achieve a sustained response to treatment with full-dose corticosteroids for a minimum duration of 4 weeks or who relapsed during steroid-tapering or after its discontinuation.
  • 18 years older.

Exclusion Criteria:

  • Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori infection or patients with systemic lupus erythematosus)
  • congestive heart failure
  • severe arrhythmia
  • nursing or pregnant women
  • aspartate aminotransferase and alanine transaminase levels ≥ 3× the upper limit of the normal threshold criteria
  • creatinine or serum bilirubin levels each 1•5 times or more than the normal range
  • active or previous malignancy
  • Unable to do blood routine test for the sake of time, distance, economic issues or other reasons.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: All-trans retinoic acid ＆Danazol
Danazol 400mg po and ATRA 10mg bid po
Drug: All-trans retinoic acid
Other Names:
  • Retinoid acid
Drug: Danazol
Other Names:
  • Danocrine
  • Cleregil
  • Danol
Active Comparator: Danazol
Danazol 400mg po
Drug: Danazol
Other Names:
  • Danocrine
  • Cleregil
  • Danol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the sustained platelet response at the 12-month follow-up
Time Frame: From the start of study treatment (Day 1) up to the end of Month 12
The number of participants (responders) with platelet count >=30x10^9/L and at least a 2-fold increase in the baseline count (PR) or a platelet count >=100x10^9/L (CR) and the absence of bleeding, without rescue medication at 12-month follow-up.
From the start of study treatment (Day 1) up to the end of Month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall response
Time Frame: From the start of study treatment (Day 1) up to the end of Month 12
The number of participants with platelet count >=30×10^9/L at least once and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy
From the start of study treatment (Day 1) up to the end of Month 12
primary response rate at 4 weeks
Time Frame: From the start of study treatment (Day 1) up to week 4 of treatment
The number of participants with platelet count >=30×10^9/L and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy at week 4 of treatment
From the start of study treatment (Day 1) up to week 4 of treatment
primary response rate at 8 weeks
Time Frame: From the start of study treatment (Day 1) up to week 8 of treatment
The number of participants with platelet count >=30×10^9/L and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy at week 8 of treatment
From the start of study treatment (Day 1) up to week 8 of treatment
time to response
Time Frame: From the start of study treatment (Day 1) up to the end of month 12
Time to response was defined as the time from starting treatment to the time to achieve the response.
From the start of study treatment (Day 1) up to the end of month 12
duration of response
Time Frame: From the start of study treatment (Day 1) up to the end of month 12
Duration of response was measured from the achievement of response to the loss of response.
From the start of study treatment (Day 1) up to the end of month 12
reduction in bleeding symptoms
Time Frame: From the start of study treatment (Day 1) up to the end of month 12
Changes of bleeding after treatment. Bleeding was defined in accordance with the WHO bleeding scale (0, no bleeding; 1, petechiae; 2, mild blood loss; 3, gross blood loss; and 4, debilitating blood loss).
From the start of study treatment (Day 1) up to the end of month 12
safety
Time Frame: From the start of study treatment (Day 1) up to the end of follow-up
All patients were assessed for safety every week during the first 8 weeks of treatment, and at 2-week intervals thereafter. Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
From the start of study treatment (Day 1) up to the end of follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University People's Hospital

Collaborators

Qilu Hospital of Shandong University
Beijing Tongren Hospital
Beijing Municipal Science & Technology Commission
Beijing Hospital
Navy General Hospital, Beijing

Investigators

  • Principal Investigator: Xiao-hui Zhang, Professor, Peking University People's Hospital, Peking University Insititute of Hematology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2012

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

February 1, 2017

Study Registration Dates

First Submitted

August 15, 2012

First Submitted That Met QC Criteria

August 16, 2012

First Posted (Estimate)

August 17, 2012

Study Record Updates

Last Update Posted (Actual)

September 7, 2017

Last Update Submitted That Met QC Criteria

September 3, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U1111-1132-6877
  • Z111107058811024 (Other Grant/Funding Number: Capital Clinical characteristic application foundation)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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