Sjogren's syndrome
Conditions
Interventions
Experimental group:Oral tofatib 5mg bid
Control group:Sequential administration of AZA by CYC (intravenous administration of CYC, oral administration of AZA 50-100mg/d)
Sponsors
Tongji Hosipital, Tongji University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18-75 years; 2. According to the 2002 or 2012 or 2016 classification criteria (see appendix 2) diagnosed as pSS; 3. Meet the diagnostic criteria of interstitial lung disease (see appendix 3); 4. Presence of exertional dyspnea, meeting Mahler dyspnea improvement index task grade 2 (see appendix 4); 5. Lung function: forced vital capacity (FVC) accounts for 45% or more of the estimated value; Diffusing capacity of carbon monoxide (DLCO) accounts for 30% or more of the estimated value; forced expiratory volume in one second (FEV1) /FVC>65%; 6. If glucocorticoid is used at the time of screening, the dose is less than 30mg/d prednisone acetate (or equivalent of other types); 7. No immunosuppressants were used (including but not limited to CYC, CsA, AZA, fk-506, methotrexate, leflurmet, mycophenolate, etc.) or no drugs were used for >=3 months at the time of screening; In patients receiving HCQ, the dose of HCQ was stable for 3 months or more; 8. Those who do not use biological agents at the time of screening (including but not limited to rituximab, infliximab, adamumab, etanercept, etc.) or who had stopped taking drugs for >=3 months; 9. The dosage of n-acetylcysteine (e.g., aminotrophia, fulushi) was stable for 3 months or more; 10. The urine pregnancy test for women of child-bearing age must be negative. From the beginning of the screening period to the last use of the study drug, both fertile women and men must voluntarily use the recognized effective contraceptive method; 11. Ability to read, understand and give written informed consent.
Exclusion criteria
Exclusion criteria: 1. Patients diagnosed as acute exacerbation of interstitial pneumonitis(AEIP); 2. Arterial blood gas analysis suggested respiratory failure; 3. Pulmonary lesions other than interstitial lung disease were associated with the following criteria: (1) Patients with moderate to severe pulmonary hypertension requiring special treatment were assessed by rheumatology specialists; (2) Smoked in the past 6 months or still smoking; (3) Patients with clinical manifestations of other severe lung diseases, such as lung masses or active lung infections; (4) Lung biopsy, alveolar lavage or HRCT suggested other serious lung lesions other than interstitial lung disease; 4. Merger of other rheumatoid immune diseases (including but not limited to rheumatoid arthritis, systemic lupus erythematosus, inflammatory myopathy, systemic sclerosis, primary biliary cirrhosis, etc.); 5. For patients with severe heart, liver, kidney and other important organs as well as diseases of blood and endocrine system, the evaluation criteria are as follows: (1) Heart disease: patients with decompensated cardiac dysfunction or refractory hypertension (hypertension that cannot control systolic and diastolic blood pressure at the target level after adequate dosage, reasonable combination, and at least three antihypertensive drugs combined with improved lifestyle and diuretics; Abnormal electrocardiogram (ECG) at the time of screening, which the investigators consider to be clinically significant and may pose an unacceptable risk to patients participating in the study; (2) Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST)>=2 ULN; (3) Renal function: renal tubules and/or renal interstitial lesions, or renal insufficiency: serum creatinine >=ULN or glomerular filtration rate (eGFR)<60ml/min/1.73m2; (4) White blood cell (WBC) count < 3 x 10^9/L (including N < 1 x 10^9/L or L < 0.5 * 10^9/L) and/or hemoglobin (Hb) < 90 g/L and/or platelet count (PLT) < 80 x 10^9/L; (5) Other serious diseases, such as tumors; 6. The presence of active infection, glucocorticoid and immunosuppressive therapy can make the condition worse; 7. Positive hepatitis b virus surface antigen, or positive hepatitis c antibody; 8. Pregnant and lactating women or those of childbearing age who cannot guarantee effective contraception; 9. People with mental disorders or other causes who cannot cooperate with treatment; 10. Allergic constitution or allergic to a variety of drugs; 11. Known allergy or intolerance to tofatib, glucocorticoid, CTX.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Forced vital capacity, FVC; | — |
Secondary
| Measure | Time frame |
|---|---|
| Lung High Resolution CT(HRCT) score;Diffusion capacity for carbon monoxide of lung(DLCO);Arterial blood gas analysis;Dyspnea score;EULAR Sjogren's Syndrome Disease Activity Index(ESSDAI);Cough symptom score;Serum concentrations of IgG, C3, C4, ANA and RF;Reduced glucocorticoid use;Glucocorticoid reduction rate, dose <=7.5mg/d maintained for more than 90 days;Peripheral immune cell spectrum;Inflammation and biomarkers in serum and sputum; | — |
Countries
China
Contacts
Public ContactWang Xuan
Tongji Hosipital, Tongji University School of Medicine
Outcome results
None listed