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

Sponsor

Peking University People's Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01667263

Collaborator

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

130

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Thrombocytopenia	Drug: All-trans retinoic acid Drug: Danazol	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

130 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

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

Actual Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Jul 1, 2016

Actual Study Completion Date :

Feb 1, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

the sustained platelet response at the 12-month follow-up [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.

Secondary Outcome Measures

overall response [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
primary response rate at 4 weeks [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 [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 [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.
duration of response [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.
reduction in bleeding symptoms [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).
safety [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Beijing Hospital, Ministry of Health	Beijing	Beijing	China	100044
2	Peking University People's Hospital, Peking University Insititute of Hematology	Beijing	Beijing	China	100044
3	Beijing Tongren Hospital	Beijing	Beijing	China
4	PLA Navy General Hospital	Beijing	Beijing	China
5	Qilu Hospital, Shandong University	Jinan	Shandong	China