Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE

Thrombocytopenia Clinical Trial

— CHORUS  

Official title:

Cyclophosphamide and Hydroxychloroquine for the Treatment of Severe Thrombocytopenia in Systemic Lupus Erythematosus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02444728
• Other study ID #: CSTAR001
• Status: Terminated
• Phase: Phase 3
• Start date: July 2015
• Est. completion date: December 30, 2018

Study information

• Verified date: February 2022
• Source: Chinese SLE Treatment And Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Treating severe thrombocytopenia is a challenge in the management of systemic lupus erythematosus. Although rheumatologists have followed some rules in real practice,there is very few evidence to support the current treatment algorithm. The purpose of this study is to compare the complete remission rate and partial remission rate of cyclophosphamide and hydroxychloroquine for treating severe thrombocytopenia in Chinese SLE patients.

Description:

This is a prospective,randomized,open-label,multi-center clinical trial. The aim of this study is to test the efficacy of GC(gluco-corticosteroid)+HCQ(hydroxychloroquine) and GC(glucocorticosteroid)+CTX(cyclophosphamide) with sequential AZA(azathioprine) in the induction and maintenance therapy of severe thrombocytopenia in SLE patients.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 50
• Est. completion date: December 30, 2018
• Est. primary completion date: December 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients fulfilled the 1997 ACR modified or SLICC classification criteria of SLE;

2. New onset thrombocytopenia: platelet count <30X109/L(by both routine test and citric acid anti-coagulated blood count test) within 3 months

Exclusion Criteria:

1. Thrombocytopenia caused by other reasons, including drugs;

2. Positive for active HAV(hepatitis A virus)/HBV(hepatitis B virus) infection

3. Active HIV(human immunodeficiency virus) or HCV(hepatitis C virus) infection;

4. Active HP(Helicopter pylori) infection;

5. Severe liver and kidney dysfunction;

6. Severe neuropsychiatric lupus;

7. No response to high dose steroid and/or cyclophosphamide 1 month prior to study enrollment;

8. Uncontrolled diabetes or hypertension before entry

9. Active GI bleeding 3 months before entry

10. Intolerant to HCQ in the past treatment history;

11. Severe bone marrow suppression or liver damage caused by cyclophosphamide in the past history;

12. Active infection , including bacteria, virus, fungi, mycobacteria

13. Allergy to any of the study medications

14. Confirmed TTP(thrombolic thrombocytopenic purpura)or CAPS(catastrophic anti-phosphilipid syndrome)

15. Platelet count less than 20X109/L with active bleeding

16. Myelodysplastic diseases

17. Patients with heart and lung function impairment

18. thiopurine S-methyltransferase (TPMT) gene positive -

Related Conditions & MeSH terms

• Thrombocytopenia

Intervention

Drug:
• Hydroxychloroquine
Hydroxychloroquine 200 mg BID for 12 months
• Cyclophosphamide
Cyclophosphamide 1000mg intravenous infusion every month for 6 months
• Azathioprine
After Cyclophosphamide treatment, Azathioprine 100mg once daily for 6 months
• Methylprednisolone
Methylprednisolone 40-50 mg once daily for 1 months and then taped for 12 months

Locations

Country	Name	City	State
China	the Affiliated Hospital to Bangbu Medical University	Bangbu	Anhui
China	Beijing Chaoyang Hospital	Beijing
China	Beijing Xuanwu Hospital	Beijing
China	Beijng Hospital	Beijing
China	China-Japan Friendship Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Sino-Japanese Friendship Hospital of Jilin University	Changchun	Jilin
China	the First Affiliated Hospital of Xiangya Medical University	Changsha	Hunan
China	the Affiliated Hospital of Inner Mongolia Medical University	Huhehaote	Inner Mongolia
China	the Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Hebei Provincial Hospital	Shijiazhuang	Hebei
China	General Hospital of Tianjing Medical University	Tianjin
China	Xinjiang Provincial Hospital	Urumqi	Xinjiang
China	the Affiliated Hospital of Xian Communication Hospital	Xian	Shanxi
China	Xijing Hospital	Xian	Shanxi

Sponsors (2)

Lead Sponsor	Collaborator
Chinese SLE Treatment And Research Group	Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (11)

Abu-Shakra M, Shoenfeld Y. Azathioprine therapy for patients with systemic lupus erythematosus. Lupus. 2001;10(3):152-3. Review. — View Citation

Arnal C, Piette JC, Léone J, Taillan B, Hachulla E, Roudot-Thoraval F, Papo T, Schaeffer A, Bierling P, Godeau B. Treatment of severe immune thrombocytopenia associated with systemic lupus erythematosus: 59 cases. J Rheumatol. 2002 Jan;29(1):75-83. — View Citation

Blasco LM. Hydroxychloroquine alone for severe immune thrombocytopenic purpura associated with systemic lupus erythematosus. Lupus. 2013 Jun;22(7):752-3. doi: 10.1177/0961203313490239. Epub 2013 May 22. — View Citation

Boumpas DT, Barez S, Klippel JH, Balow JE. Intermittent cyclophosphamide for the treatment of autoimmune thrombocytopenia in systemic lupus erythematosus. Ann Intern Med. 1990 May 1;112(9):674-7. — View Citation

Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, Wong WS, Cheng G. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28;349(9):831-6. — View Citation

Contreras G, Tozman E, Nahar N, Metz D. Maintenance therapies for proliferative lupus nephritis: mycophenolate mofetil, azathioprine and intravenous cyclophosphamide. Lupus. 2005;14 Suppl 1:s33-8. — View Citation

Khellaf M, Chabrol A, Mahevas M, Roudot-Thoraval F, Limal N, Languille L, Bierling P, Michel M, Godeau B. Hydroxychloroquine is a good second-line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies. Am J Hematol. 2014 Fe — View Citation

Levine AB, Erkan D. Clinical assessment and management of cytopenias in lupus patients. Curr Rheumatol Rep. 2011 Aug;13(4):291-9. doi: 10.1007/s11926-011-0179-5. Review. — View Citation

Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011 Apr 21;117(16):4190-207. doi: 10.1182/bloo — View Citation

Newman K, Owlia MB, El-Hemaidi I, Akhtari M. Management of immune cytopenias in patients with systemic lupus erythematosus - Old and new. Autoimmun Rev. 2013 May;12(7):784-91. doi: 10.1016/j.autrev.2013.02.001. Epub 2013 Feb 24. Review. — View Citation

Roach BA, Hutchinson GJ. Treatment of refractory, systemic lupus erythematosus-associated thrombocytopenia with intermittent low-dose intravenous cyclophosphamide. Arthritis Rheum. 1993 May;36(5):682-4. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	complete remission rate	percentage of patients whose platelet count > 100X109/L	at 12 month
Secondary	partial remission rate	percentage of patients whose platelet increase to >30X109/L or with at least a two folds increase of the baseline(ie, pretreatment) count and the absence of bleeding	at 12 month