CHORUS: Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE

Sponsor

Chinese SLE Treatment And Research Group (Other)

Overall Status

Terminated

CT.gov ID

NCT02444728

Collaborator

Peking Union Medical College Hospital (Other)

Enrollment

Locations

Arms

Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Thrombocytopenia	Drug: Hydroxychloroquine Drug: Cyclophosphamide Drug: Azathioprine Drug: Methylprednisolone	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2015

Actual Primary Completion Date :

Dec 30, 2018

Actual Study Completion Date :

Dec 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group1:Hydroxychloroquine Hydroxychloroquine: 100 mg tablets by mouth, 400mg everyday for 12 months Methylprednisolone: 4 mg tablets by mouth, 40-50mg everyday and tapering for 12 months	Drug: Hydroxychloroquine Hydroxychloroquine 200 mg BID for 12 months Other Names: Fenle Drug: Methylprednisolone Methylprednisolone 40-50 mg once daily for 1 months and then taped for 12 months Other Names: meizhuole
Active Comparator: Group 2:Cyclophosphamide Cyclophosphamide, Azathioprine & Methylprednisolone Cyclophosphamide: 200mg powder intravenous infusion, 1000mg every month for 6 month. Azathioprine: 100 mg tablets by mouth, everyday for 6 months. Methylprednisolone: 4 mg tablets by mouth, 40-50mg everyday and tapering for 12 months	Drug: Hydroxychloroquine Hydroxychloroquine 200 mg BID for 12 months Other Names: Fenle Drug: Cyclophosphamide Cyclophosphamide 1000mg intravenous infusion every month for 6 months Other Names: Huanlinxianan Drug: Azathioprine After Cyclophosphamide treatment, Azathioprine 100mg once daily for 6 months Other Names: liuzuopiaolin Drug: Methylprednisolone Methylprednisolone 40-50 mg once daily for 1 months and then taped for 12 months Other Names: meizhuole

Arm

Intervention/Treatment

Active Comparator: Group1:Hydroxychloroquine

Hydroxychloroquine: 100 mg tablets by mouth, 400mg everyday for 12 months Methylprednisolone: 4 mg tablets by mouth, 40-50mg everyday and tapering for 12 months

Drug: Hydroxychloroquine

Hydroxychloroquine 200 mg BID for 12 months

Other Names:

Fenle

Drug: Methylprednisolone

Methylprednisolone 40-50 mg once daily for 1 months and then taped for 12 months

Other Names:

meizhuole

Active Comparator: Group 2:Cyclophosphamide

Cyclophosphamide, Azathioprine & Methylprednisolone Cyclophosphamide: 200mg powder intravenous infusion, 1000mg every month for 6 month. Azathioprine: 100 mg tablets by mouth, everyday for 6 months. Methylprednisolone: 4 mg tablets by mouth, 40-50mg everyday and tapering for 12 months

Drug: Hydroxychloroquine

Hydroxychloroquine 200 mg BID for 12 months

Other Names:

Fenle

Drug: Cyclophosphamide

Cyclophosphamide 1000mg intravenous infusion every month for 6 months

Other Names:

Huanlinxianan

Drug: Azathioprine

After Cyclophosphamide treatment, Azathioprine 100mg once daily for 6 months

Other Names:

liuzuopiaolin

Drug: Methylprednisolone

Methylprednisolone 40-50 mg once daily for 1 months and then taped for 12 months

Other Names:

meizhuole

Outcome Measures

Primary Outcome Measures

complete remission rate [at 12 month]
percentage of patients whose platelet count > 100X109/L

Secondary Outcome Measures

partial remission rate [at 12 month]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients fulfilled the 1997 ACR modified or SLICC classification criteria of SLE；
New onset thrombocytopenia: platelet count <30X109/L(by both routine test and citric acid anti-coagulated blood count test) within 3 months

Exclusion Criteria:

Thrombocytopenia caused by other reasons, including drugs；
Positive for active HAV(hepatitis A virus)/HBV(hepatitis B virus) infection
Active HIV(human immunodeficiency virus) or HCV(hepatitis C virus) infection;
Active HP(Helicopter pylori) infection;
Severe liver and kidney dysfunction；
Severe neuropsychiatric lupus；
No response to high dose steroid and/or cyclophosphamide 1 month prior to study enrollment；
Uncontrolled diabetes or hypertension before entry
Active GI bleeding 3 months before entry
Intolerant to HCQ in the past treatment history；
Severe bone marrow suppression or liver damage caused by cyclophosphamide in the past history；
Active infection , including bacteria, virus, fungi, mycobacteria
Allergy to any of the study medications
Confirmed TTP(thrombolic thrombocytopenic purpura)or CAPS(catastrophic anti-phosphilipid syndrome)
Platelet count less than 20X109/L with active bleeding
Myelodysplastic diseases
Patients with heart and lung function impairment
thiopurine S-methyltransferase (TPMT) gene positive -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	the Affiliated Hospital to Bangbu Medical University	Bangbu	Anhui	China	233000
2	Hebei Provincial Hospital	Shijiazhuang	Hebei	China	050051
3	the First Affiliated Hospital of Xiangya Medical University	Changsha	Hunan	China	410000
4	the Affiliated Hospital of Inner Mongolia Medical University	Huhehaote	Inner Mongolia	China	010050
5	Sino-Japanese Friendship Hospital of Jilin University	Changchun	Jilin	China	410008
6	the Affiliated Hospital of Xian Communication Hospital	Xian	Shanxi	China	710000
7	Xijing Hospital	Xian	Shanxi	China	710032
8	Xinjiang Provincial Hospital	Urumqi	Xinjiang	China	830001
9	the Affiliated Hospital of Kunming Medical University	Kunming	Yunnan	China	650032
10	Beijng Hospital	Beijing		China	100006
11	Beijing Chaoyang Hospital	Beijing		China	100020
12	China-Japan Friendship Hospital	Beijing		China	100029
13	Peking Union Medical College Hospital	Beijing		China	100032
14	Beijing Xuanwu Hospital	Beijing		China	100053
15	General Hospital of Tianjing Medical University	Tianjin		China	300052

Sponsors and Collaborators

Chinese SLE Treatment And Research Group
Peking Union Medical College Hospital

Investigators

Principal Investigator: Xiaofeng Zeng, MD, Chinese SLE Treatment And Research Group
Study Chair: Xiaofeng Zeng, MD, Peking Union Medical College Hospital
Principal Investigator: Xinping Tian, MD, Peking Union Medical College Hospital