The Efficacy and Safety of Tacrolimus in Refractory Rheumatoid Arthritis Patients for 6 Months and Long-term Treatment

NCT02837978 | Completed Phase 4

• 1 other identifier: Tacrolimus RA QiluH
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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

Conditions

Arthritis, Rheumatoid

Keywords

Arthritis, Rheumatoid; Tacrolimus; Treatment outcome; Safety

Outcome Measures

Primary Outcomes (1)

• Change from baseline Disease Activity Score 28 (DAS28-ESR) at 24 and longer weeks.

  Change from baseline Disease Activity Score 28 (DAS28) erythrocyte sedimentation rate (ESR) at 24 and longer weeks.

  12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week

Secondary Outcomes (14)

• Change from baseline ACR20 response rate at 24 and longer weeks.

  12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week

• The clinical remission rate at 24 and longer weeks.

  12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week

• Clinical response was analyzed using the European League Against Rheumatism (EULAR) improvement criteria.

  12 week,3 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week

• Change from baseline Simplified Disease Activity Index (SDAI) at 24 and longer weeks.

  12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week

• Change from baseline Clinical disease activity index (CDAI) at 24 and longer weeks.

  12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week

Study Arms (2)

Tacrolimus group

EXPERIMENTAL

RA patients treated with tacrolimus, without MTX

Drug: Tacrolimus

Tacrolimus + MTX group

ACTIVE COMPARATOR

RA patients treated with tacrolimus and MTX

Drug: Tacrolimus; Drug: MTX

Interventions

Tacrolimus DRUG

Tacrolimus capsule: 0.5mg to 1mg, po, twice per day (Bid)，adjusted by its concentration in blood or due to patient response. Then may titer down until the endpoint.

Also known as: FK506

Tacrolimus + MTX group; Tacrolimus group

MTX DRUG

MTX：5mg to 15mg, po, once per week (Qw) until the endpoint or adjusted due to unacceptable toxicity develops.

Also known as: methotrexate

Tacrolimus + MTX group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed based on 1987 ACR classification criteria for rheumatoid arthritis;
• Age ≥18 years;
• 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;
• Medium or high disease activity (DAS28≥3.2);
• Extra-articular manifestations (such as pulmonary fibrosis, proteinuria, leukopenia and peripheral neuropathy ) of RA patients are stable or no significant progress;
• Dose of prednisone and NSAIDs remain stable for at least one month.

You may not qualify if:

• Patients with acute or chronic infections such as active bacterial, viral, fungal, tuberculosis infection or active hepatitis B;
• Platelet counts(PLT) \<80 x 10\^9 / L, or white blood cell (WBC) \<3 x 10\^9 / L;
• Propionate acid aminotransferase (ALT) or aspartate aminotransferase (AST) is two times higher than the upper limit of normal;
• Renal insufficiency: serum Cr ≥ 176 umol / L;
• Pregnant or nursing women (breastfeeding) ；
• Patients has a history of malignancy (cure time in less than 5 years);
• Patients with severe or poorly controlled hypertension, diabetes or cardiac dysfunction;
• 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.

Sponsors & Collaborators

• Qiang Shu: lead

Study Sites (1)

Qilu Hospital

Jinan, Shandong, 250012, China

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Tacrolimus; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Qiang Shu, Dr.

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 20, 2016
• Study Start: January 1, 2015
• Primary Completion: September 30, 2022
• Study Completion: December 30, 2022
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)