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

• ClinicalTrials.gov Identifier: NCT01882127
• Recruitment Status: Withdrawn
• First Posted: June 20, 2013
• Last Update Posted: April 20, 2016
• Sponsor: Shandong University
• Information provided by (Responsible Party): Ming Hou, Shandong University

Tracking Information

• First Submitted Date: April 19, 2013
• First Posted Date: June 20, 2013
• Last Update Posted Date: April 20, 2016
• Study Start Date: February 2013
• Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 17, 2013)

Platelet count [ Time Frame: up to six months per subject ]

The outcome should be classified into one of the following descriptions accordingly :

1. CR. A complete response (CR) was defined as a sustained (≥ 3 months) platelet count ≥ 100×10^9/L.
2. R. A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10^9/L without recurrence of thrombocytopenia.
3. 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.
4. Relapse.A relapse was defined as platelet count falls below 30×10^9/L or bleeding accrues after achieving R or CR.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures (submitted: June 17, 2013): Bleeding episodes [ Time Frame: up to six months per subject ]
• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: All-Trans Retinoic Acid (ATRA) Combining Dexamethasone Versus High-dose Dexamethasone for Initial Treatment of Primary Immune Thrombocytopenia (ITP)
• 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)
• Brief 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.
• Detailed 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
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Purpura
• Idiopathic Thrombocytopenic Purpura

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).
  Other Names:

  • Acid, trans-Retinoic
  • trans Retinoic Acid
  • all-trans-Retinoic Acid
  • Acid, all-trans-Retinoic
  • all trans Retinoic Acid
• Drug: 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).

Study Arms

• Active Comparator: High dose-DEX
  40 patients are enrolled to take dexamethasone orally at a dose of 40 mg daily for 4 days
  Intervention: Drug: Dexamethasone
• Experimental: ATRA & High dose-DEX
  40 patients are enrolled to take Dexamethasone orally at 40mg a day for 4 days and all-trans retinoic acid at 10mg tablet every 8 hours a day for 12 consecutive weeks.
  Interventions:

  • Drug: All-Trans Retinoid Acid(ATRA)
  • Drug: Dexamethasone

Publications *

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

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: April 18, 2016): 0
• Original Estimated Enrollment (submitted: June 17, 2013): 80
• Study Completion Date: Not Provided
• Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT01882127
• Other Study ID Numbers: ITP-009
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Ming Hou, Shandong University
• Study Sponsor: Shandong University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ming Hou, Dr; Shandong University

• PRS Account: Shandong University
• Verification Date: June 2013