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

NCT01882127 | Withdrawn Phase 3 DMC

• 1 other identifier: ITP-009
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Purpura; Idiopathic Thrombocytopenic Purpura

Keywords

Purpura; Idiopathic Thrombocytopenic Purpura

Outcome Measures

Primary Outcomes (1)

• Platelet count

  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.

  up to six months per subject

Other Outcomes (1)

• Bleeding episodes

  up to six months per subject

Study Arms (2)

High dose-DEX

ACTIVE COMPARATOR

40 patients are enrolled to take dexamethasone orally at a dose of 40 mg daily for 4 days

Drug: Dexamethasone

ATRA & High dose-DEX

EXPERIMENTAL

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.

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

Interventions

All-Trans Retinoid Acid(ATRA) DRUG

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).

Also known as: Acid, trans-Retinoic, trans Retinoic Acid, all-trans-Retinoic Acid, Acid, all-trans-Retinoic, all trans Retinoic Acid

ATRA & High dose-DEX

Dexamethasone DRUG

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).

ATRA & High dose-DEX; High dose-DEX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet the diagnostic criteria for immune thrombocytopenia.
• Untreated hospitalized patients, may be male or female, between the ages of 18 \~ 80 years.
• To show a platelet count \< 30×10\^9/L, and with bleeding manifestations.
• Eastern Cooperative Oncology Group（ECOG）performance status ≤ 2.
• Willing and able to sign written informed consent

You may not qualify if:

• Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 3 months before the screening visit.
• Received high-dose steroids or \[2\] intravenous immunoglobulin transfusion(IVIG)in the 3 weeks prior to the start of the study.
• 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)
• Female patients who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period.
• 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.
• Patients who are deemed unsuitable for the study by the investigator.

Sponsors & Collaborators

• Shandong University: lead

Study Sites (1)

Qilu Hospital, Shandong University

Jinan, Shandong, 250000, China

Location

Related Publications (4)

• Toth K, Sarang Z, Scholtz B, Brazda P, Ghyselinck N, Chambon P, Fesus 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.

  PMID: 21072052 BACKGROUND

• Tancini G, Marchini S. Adriamycin plus cyclophosphamide in advanced bronchial carcinoma. Tumori. 1976 Jul-Aug;62(4):373-5. doi: 10.1177/030089167606200403.

  PMID: 1020044 BACKGROUND

• 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. doi: 10.1111/j.1600-0609.1999.tb01736.x.

  PMID: 10089890 BACKGROUND

• 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.

  PMID: 8547658 BACKGROUND

MeSH Terms

Conditions

Purpura; Purpura, Thrombocytopenic, Idiopathic

Interventions

Tretinoin; Dexamethasone

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Purpura, Thrombocytopenic; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Ming Hou, Dr

  Shandong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director

Study Record Dates

• First Submitted: April 19, 2013
• First Posted: June 20, 2013
• Study Start: February 1, 2013
• Primary Completion: December 1, 2014
• Last Updated: April 20, 2016

Record last verified: 2013-06

Locations

CN (1)