Clinical trial NCT02837978: The Efficacy and Safety of Tacrolimus in Refractory Rheumatoid Arthritis Patients for 6 Months and Long-term Treatment
Official title: Prospective Clinical Study to Observe the Efficacy and Safety of Tacrolimus in Refractory Rheumatoid Arthritis Patients for 6 Months Treatment in China
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arthritis, Rheumatoid
Keywords: Arthritis, Rheumatoid
Tacrolimus
Treatment outcome
Safety
Lead sponsor: Qilu Hospital of Shandong University
Sponsor class: OTHER
First posted: 2016-07-20
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to observed prospectively the efficacy and safety of 6 months and long-term treatment of Tacrolimus alone or with methotrexate (MTX) in moderate and severe Chinese RA patients who shown insufficiency response or intolerance to DMARDs

Detailed description: This study will enroll 150 cases of refractory rheumatoid arthritis (RA) patients in Chinese，who are in moderate or severe disease activity and insufficiency response or intolerance to DMARDs. The participants plan to be treated with Tacrolimus alone, or along with methotrexate (MTX) if participants were tolerant to MTX. The efficacy and safety of 6 month Tacrolimus treatment in RA patients will be evaluated with DAS28 and other disease activity indices.

Eligibility criteria: Inclusion Criteria:

1. Patients diagnosed based on 1987 ACR classification criteria for rheumatoid arthritis;
2. Age ≥18 years;
3. Patients have a history of DMARDs including csDMARDs（methotrexate，leflunomide, hydroxychloroquine, iguratimod, sulfasalazine) or any biologic DMARDs（TNFi，tocilizumab or Tofacitinib），prednisone or Chinese traditional Medicine（tripterygium Glycosides，Sinomenine）for 3 months, but couldn't achieve clinical remission， or couldn't tolerate one or more DMARDs;
4. Medium or high disease activity (DAS28≥3.2);
5. Extra-articular manifestations (such as pulmonary fibrosis, proteinuria, leukopenia and peripheral neuropathy ) of RA patients are stable or no significant progress;
6. Dose of prednisone and NSAIDs remain stable for at least one month.

Exclusion Criteria:

1. Patients with acute or chronic infections such as active bacterial, viral, fungal, tuberculosis infection or active hepatitis B;
2. Platelet counts(PLT) \<80 x 10\^9 / L, or white blood cell (WBC) \<3 x 10\^9 / L;
3. Propionate acid aminotransferase (ALT) or aspartate aminotransferase (AST) is two times higher than the upper limit of normal;
4. Renal insufficiency: serum Cr ≥ 176 umol / L;
5. Pregnant or nursing women (breastfeeding) ；
6. Patients has a history of malignancy (cure time in less than 5 years);
7. Patients with severe or poorly controlled hypertension, diabetes or cardiac dysfunction;
8. Other comorbidities that cannot be treated with immune suppressants. In addition, once patients experience severe adverse drug reactions、ineffective treatment or rapid progression of rheumatoid arthritis, then quit this research.

Primary outcomes:
measure: Change from baseline Disease Activity Score 28 (DAS28-ESR) at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Secondary outcomes:
measure: Change from baseline ACR20 response rate at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: The clinical remission rate at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Clinical response was analyzed using the European League Against Rheumatism (EULAR) improvement criteria.
timeFrame: 12 week,3 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Change from baseline Simplified Disease Activity Index (SDAI) at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Change from baseline Clinical disease activity index (CDAI) at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Change from baseline Erythrocyte Sedimentation Rate (ESR) at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Change from baseline C-Reactive Protein (CRP) at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Change from baseline swollen joint number (SW28) at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Change from baseline tenderness joint number (T28) at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Change from baseline patient global assessment(PGA) at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Change from baseline physician global assessment(PHGA) at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Change from baseline Health Assessment Questionnaire (HAQ) at 24 and longer weeks.
timeFrame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
measure: Safety assessed by Adverse Events (AEs)
timeFrame: Up to 144 weeks
measure: Safety assessed by incidence of serious adverse events (SAE)
timeFrame: Up to 144 weeks
Other outcomes:
Locations:
city: Jinan
country: China
facility: Qilu Hospital
state: Shandong
Study officials:
affiliation: Qilu Hospital of Shandong University
name: Qiang Shu, Dr.
role: PRINCIPAL_INVESTIGATOR
References: