All-Trans Retinoic Acid (ATRA) Combining Dexamethasone Versus High-dose Dexamethasone for Initial Treatment of Primary Immune Thrombocytopenia (ITP)

Idiopathic Thrombocytopenic Purpura Clinical Trial

Official title:

Clinical Study on All-Trans Retinoic Acid (ATRA) Combining High-dose Dexamethasone Versus High-dose Dexamethasone Alone for Initial Treatment of Primary Immune Thrombocytopenia (ITP)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01882127
• Other study ID #: ITP-009
• Status: Withdrawn
• Phase: Phase 3
• First received: April 19, 2013
• Last updated: April 18, 2016
• Start date: February 2013

Study information

• Verified date: June 2013
• Source: Shandong University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The project was undertaking by Qilu Hospital of Shandong University in China. In order to report the efficacy and safety of All-Trans Retinoic Acid (ATRA) combining with High-dose Dexamethasone for the treatment of adults with primary immune thrombocytopenia (ITP), compared to conventional high-dose dexamethasone therapy.

Description:

The investigators are undertaking a parallel group, randomised controlled trial of 80 primary ITP adult patients from Qilu Hospital of Shandong University in China. One part of the participants are randomly selected to receive All-Trans Retinoic Acid(10mg tablet by mouth every 8 hours a day for 12 consecutive weeks, combining with dexamethasone (given orally at a dose of 40 mg per day for 4 days, the others are selected to receive high-dose of dexamethasone treatment (given orally at a dose of 40 mg daily for 4 days). Patients were monitored every 1 to 3 days at the first two weeks and every 1 to 4 weeks afterwards for platelet counts, and were monitored every 1 month for transaminitis and other side effects

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Meet the diagnostic criteria for immune thrombocytopenia.

2. Untreated hospitalized patients, may be male or female, between the ages of 18 ~ 80 years.

3. To show a platelet count < 30×10^9/L, and with bleeding manifestations.

4. Eastern Cooperative Oncology Group(ECOG)performance status = 2.

5. Willing and able to sign written informed consent

Exclusion Criteria:

1. Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 3 months before the screening visit.

2. Received high-dose steroids or [2] intravenous immunoglobulin transfusion(IVIG)in the 3 weeks prior to the start of the study.

3. Current HIV infection or hepatitis B virus or hepatitis C virus infections. Severe medical condition (lung, hepatic or renal disorder) other than ITP. 4.Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia)

5.Female patients who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period.

6.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.

7.Patients who are deemed unsuitable for the study by the investigator.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Idiopathic Thrombocytopenic Purpura
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia
• Thrombocytosis

Intervention

Drug:
• All-Trans Retinoid Acid(ATRA)
patients in ATRA&High dose-DEX group take All-Trans Retinoic Acid(orally,10mg every 8 hours a day for 12 consecutive weeks) in combination with dexamethasone(intravenously , 40mg/d for 4 consecutive days).
• Dexamethasone
Patients in High dose-DEX treatment group take dexamethasone( orally , 40mg daily for 4 days),patients in ATRA&High dose-DEX group take All-Trans Retinoic Acid(orally,10mg every 8 hours a day for 12 consecutive weeks) in combination with dexamethasone(intravenously , 40mg/d for 4 consecutive days).

Locations

Country	Name	City	State
China	Qilu Hospital, Shandong University	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Shandong University

Country where clinical trial is conducted

China, 

References & Publications (4)

Chen YH, Desai P, Shiao RT, Lavelle D, Haleem A, Chen J. Inhibition of myeloma cell growth by dexamethasone and all-trans retinoic acid: synergy through modulation of interleukin-6 autocrine loop at multiple sites. Blood. 1996 Jan 1;87(1):314-23. — View Citation

Tancini G, Marchini S. Adriamycin plus cyclophosphamide in advanced bronchial carcinoma. Tumori. 1976 Jul-Aug;62(4):373-5. — View Citation

Tosi P, Pellacani A, Visani G, Ottaviani E, Ronconi S, Zamagni E, Benni M, Cavo M, Tura S. In vitro treatment with retinoids decreases bcl-2 protein expression and enhances dexamethasone-induced cytotoxicity and apoptosis in multiple myeloma cells. Eur J Haematol. 1999 Mar;62(3):143-8. — View Citation

Tóth K, Sarang Z, Scholtz B, Brázda P, Ghyselinck N, Chambon P, Fésüs L, Szondy Z. Retinoids enhance glucocorticoid-induced apoptosis of T cells by facilitating glucocorticoid receptor-mediated transcription. Cell Death Differ. 2011 May;18(5):783-92. doi: 10.1038/cdd.2010.136. Epub 2010 Nov 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Bleeding episodes		up to six months per subject	Yes
Primary	Platelet count	The outcome should be classified into one of the following descriptions accordingly : CR. A complete response (CR) was defined as a sustained (= 3 months) platelet count = 100×10^9/L.; R. A response (R) was defined as a sustained (= 3 months) platelet count = 30×10^9/L without recurrence of thrombocytopenia.; NR.No response (NR) was defined as platelet count < 30 × 10^9/L or a less than two fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on two occasions more than a day apart.; Relapse.A relapse was defined as platelet count falls below 30×10^9/L or bleeding accrues after achieving R or CR.	up to six months per subject	Yes