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

This study has been completed.
Sponsor:
Collaborators:
Beijing Municipal Science & Technology Commission
Beijing Hospital
Qilu Hospital
Navy General Hospital, Beijing
Beijing Tongren Hospital
Information provided by (Responsible Party):
Xiao-hui Zhang, Peking University People's Hospital
ClinicalTrials.gov Identifier:
NCT01667263
First received: August 15, 2012
Last updated: February 10, 2017
Last verified: February 2017
  Purpose
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.

Condition Intervention Phase
Autoimmune Thrombocytopenia
Drug: All-trance retinoid acid
Drug: Danazol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Peking University People's Hospital:

Primary Outcome Measures:
  • the sustained platelet response at the 6-month follow-up [ Time Frame: From the start of study treatment (Day 1) up to the end of Month 6 ]
    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 6-month follow-up.


Secondary Outcome Measures:
  • overall response [ Time Frame: From the start of study treatment (Day 1) up to the end of Month 6 ]
    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

  • 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

  • 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

  • time to response [ Time Frame: From the start of study treatment (Day 1) up to the end of month 6 ]
    Time to response was defined as the time from starting treatment to the time to achieve the response.

  • duration of response [ Time Frame: From the start of study treatment (Day 1) up to the end of month 6 ]
    Duration of response was measured from the achievement of response to the loss of response.

  • reduction in bleeding symptoms [ Time Frame: From the start of study treatment (Day 1) up to the end of month 6 ]
    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).

  • safety [ Time Frame: From the start of study treatment (Day 1) up to the end of month 6 ]
    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


Enrollment: 95
Actual Study Start Date: June 1, 2012
Study Completion Date: February 1, 2017
Primary Completion Date: July 1, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All-trance retinoid acid &Danazol
Danazol 400mg po and all-trance retinoid acid 10mg bid po
Drug: All-trance retinoid acid
Other Name: Retinoid acid
Drug: Danazol
Other Names:
  • Danocrine
  • Cleregil
  • Danol
Active Comparator: Danazol
Danazol 400mg po
Drug: Danazol
Other Names:
  • Danocrine
  • Cleregil
  • Danol

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01667263

Locations
China, Beijing
Beijing Hospital, Ministry of Health
Beijing, Beijing, China, 100044
Peking University People's Hospital, Peking University Insititute of Hematology
Beijing, Beijing, China, 100044
Beijing Tongren Hospital
Beijing, Beijing, China
PLA Navy General Hospital
Beijing, Beijing, China
China, Shandong
Qilu Hospital, Shandong University
Jinan, Shandong, China
Sponsors and Collaborators
Peking University People's Hospital
Beijing Municipal Science & Technology Commission
Beijing Hospital
Qilu Hospital
Navy General Hospital, Beijing
Beijing Tongren Hospital
Investigators
Principal Investigator: Xiao-Hui Zhang, Professor Peking University People's Hospital, Peking University Insititute of Hematology
  More Information

Publications:
LIU Wen-bin, WANG Zhao-yue, CAO Li-juan, ZHAO Xiao-juan, ZHU Ming-qing, BAI Xia, RUAN Chang-geng.Therapeutic Effect and Mechanism of All-trans-retinoic Acid Treatment in Refractory Idiopathic Thrombocytopenic Purpura.Suzhou University Journal of Medical Science.2009;3 476-479.

Responsible Party: Xiao-hui Zhang, Professor, Peking University People's Hospital
ClinicalTrials.gov Identifier: NCT01667263     History of Changes
Other Study ID Numbers: U1111-1132-6877  Z111107058811024 
Study First Received: August 15, 2012
Last Updated: February 10, 2017

Keywords provided by Peking University People's Hospital:
all-trans retinoid acid
primary immune thrombocytopenia
corticosteroid-resistant
refractory
danazol

Additional relevant MeSH terms:
Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Danazol
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 24, 2017