Clinical trial NCT01667263: The Combination of ATRA and Danazol as Second-line Treatment in Adult Immune Thrombocytopenia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autoimmune Thrombocytopenia
Keywords: All-trans retinoic acid
primary immune thrombocytopenia
corticosteroid-resistant
refractory
danazol
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Municipal Science & Technology Commission
name: Beijing Hospital
name: Qilu Hospital of Shandong University
name: Navy General Hospital, Beijing
name: Beijing Tongren Hospital
First posted: 2012-08-17
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: the sustained platelet response at the 12-month follow-up
timeFrame: From the start of study treatment (Day 1) up to the end of Month 12
Secondary outcomes:
measure: overall response
timeFrame: From the start of study treatment (Day 1) up to the end of Month 12
measure: primary response rate at 4 weeks
timeFrame: From the start of study treatment (Day 1) up to week 4 of treatment
measure: primary response rate at 8 weeks
timeFrame: From the start of study treatment (Day 1) up to week 8 of treatment
measure: time to response
timeFrame: From the start of study treatment (Day 1) up to the end of month 12
measure: duration of response
timeFrame: From the start of study treatment (Day 1) up to the end of month 12
measure: reduction in bleeding symptoms
timeFrame: From the start of study treatment (Day 1) up to the end of month 12
measure: safety
timeFrame: From the start of study treatment (Day 1) up to the end of follow-up
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital, Ministry of Health
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital, Peking University Insititute of Hematology
state: Beijing
city: Beijing
country: China
facility: Beijing Tongren Hospital
state: Beijing
city: Beijing
country: China
facility: PLA Navy General Hospital
state: Beijing
city: Jinan
country: China
facility: Qilu Hospital, Shandong University
state: Shandong
Study officials:
affiliation: Peking University People's Hospital, Peking University Insititute of Hematology
name: Xiao-Hui Zhang, Professor
role: PRINCIPAL_INVESTIGATOR
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citation: 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.
citation: 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.
citation: Feng FE, Feng R, Wang M, Zhang JM, Jiang H, Jiang Q, Lu J, Liu H, Peng J, Hou M, Shen JL, Wang JW, Xu LP, Liu KY, Huang XJ, Zhang XH. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial. Lancet Haematol. 2017 Oct;4(10):e487-e496. doi: 10.1016/S2352-3026(17)30170-9. Epub 2017 Sep 13.