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Autoimmune ThrombocytopeniaPhase 2NCT01667263

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

A Phase 2 study testing All-trans retinoic acid and Danazol in people with Autoimmune Thrombocytopenia, run by Peking University People's Hospital at 5 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Autoimmune Thrombocytopenia
What is being tested?
All-trans retinoic acid and Danazol
Could I receive a placebo?
No, everyone receives an active treatment
How many people
130 participants
Where
5 sitesChina
Study dates
1 Jun 2012to 1 Feb 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

China5 sites

  • Beijing Hospital, Ministry of Health

    Beijing, Beijing Municipality, 100044

  • Peking University People's Hospital, Peking University Insititute of Hematology

    Beijing, Beijing Municipality, 100044

  • Beijing Tongren Hospital

    Beijing, Beijing Municipality

  • PLA Navy General Hospital

    Beijing, Beijing Municipality

  • Qilu Hospital, Shandong University

    Jinan, Shandong

Other trials in China

About this study

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

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.

Read the 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.

Being tested
All-trans retinoic acid, Danazol
Keywords
All-trans retinoic acid, primary immune thrombocytopenia, corticosteroid-resistant, refractory, danazol
Medical subject headings
Purpura, Thrombocytopenic, Idiopathic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • All-trans retinoic acidDrug

    Also called Retinoid acid

  • DanazolDrug

    Also called Danocrine, Cleregil, Danol

Study groups in NCT01667263
Study groupRoleWhat they receive
All-trans retinoic acid ＆DanazolExperimentalDanazol 400mg po and ATRA 10mg bid po
Receives: Drug: All-trans retinoic acid; Drug: Danazol
DanazolActive comparatorDanazol 400mg po
Receives: Drug: Danazol

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: From the start of study treatment (Day 1) up to the end of Month 12

Secondary outcomes (7)

  1. overall response

    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

    Measured: From the start of study treatment (Day 1) up to the end of Month 12

  2. primary response rate at 4 weeks

    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

    Measured: From the start of study treatment (Day 1) up to week 4 of treatment

  3. primary response rate at 8 weeks

    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

    Measured: From the start of study treatment (Day 1) up to week 8 of treatment

  4. time to response

    Time to response was defined as the time from starting treatment to the time to achieve the response.

    Measured: From the start of study treatment (Day 1) up to the end of month 12

  5. duration of response

    Duration of response was measured from the achievement of response to the loss of response.

    Measured: From the start of study treatment (Day 1) up to the end of month 12

  6. reduction in bleeding symptoms

    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).

    Measured: From the start of study treatment (Day 1) up to the end of month 12

  7. safety

    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

    Measured: From the start of study treatment (Day 1) up to the end of follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Aug 2012 (estimated)
  2. Study start1 Jun 2012
  3. Primary completion1 Jul 2016
  4. Study completion1 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
130 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01667263
Sponsor's protocol ID
U1111-1132-6877
Other IDs
Z111107058811024
Status last verified
Apr 2017
First submitted
15 Aug 2012
Last updated
7 Sep 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Zhang X, Fu H, Xu L, Liu D, Wang J, Liu K, Huang X. Prolonged thrombocytopenia following allogeneic hematopoietic stem cell transplantation and its association with a reduction in ploidy and an immaturation of megakaryocytes. Biol Blood Marrow Transplant. 2011 Feb;17(2):274-80. doi: 10.1016/j.bbmt.2010.09.007. Epub 2010 Sep 18.

    PubMed 20854919

  • Nozaki Y, Tamaki C, Yamagata T, Sugiyama M, Ikoma S, Kinoshita K, Funauchi M. All-trans-retinoic acid suppresses interferon-gamma and tumor necrosis factor-alpha; a possible therapeutic agent for rheumatoid arthritis. Rheumatol Int. 2006 Jul;26(9):810-7. doi: 10.1007/s00296-005-0076-1. Epub 2005 Nov 15.

    PubMed 16292516

  • Sakakura M, Wada H, Tawara I, Nobori T, Sugiyama T, Sagawa N, Shiku H. Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura. Thromb Res. 2007;120(2):187-93. doi: 10.1016/j.thromres.2006.09.008. Epub 2006 Oct 24.

    PubMed 17067661

  • Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008 Mar 1;111(5):2505-15. doi: 10.1182/blood-2007-07-102798.

    PubMed 18299451

  • Wing K, Larsson P, Sandstrom K, Lundin SB, Suri-Payer E, Rudin A. CD4+ CD25+ FOXP3+ regulatory T cells from human thymus and cord blood suppress antigen-specific T cell responses. Immunology. 2005 Aug;115(4):516-25. doi: 10.1111/j.1365-2567.2005.02186.x.

    PubMed 16011520

  • 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.

    PubMed 19005182

  • 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.

  • 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.

    PubMed 28917657

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing All-trans retinoic acid and Danazol in people with Autoimmune Thrombocytopenia, run by Peking University People's Hospital at 5 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

the sustained platelet response at the 12-month follow-up (time frame: From the start of study treatment (Day 1) up to the end of Month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01667263, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2017.

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