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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02837978
Recruitment Status : Recruiting
First Posted : July 20, 2016
Last Update Posted : October 9, 2020
Sponsor:
Information provided by (Responsible Party):
Qiang Shu, Qilu Hospital of Shandong University

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

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: Tacrolimus Drug: MTX Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: 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
Actual Study Start Date : January 2015
Estimated Primary Completion Date : October 30, 2020
Estimated Study Completion Date : January 30, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
Experimental: Tacrolimus group
RA patients treated with tacrolimus, without MTX
Drug: Tacrolimus
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.
Other Name: FK506

Active Comparator: Tacrolimus + MTX group
RA patients treated with tacrolimus and MTX
Drug: Tacrolimus
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.
Other Name: FK506

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




Primary Outcome Measures :
  1. Change from baseline Disease Activity Score 28 (DAS28-ESR) at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline Disease Activity Score 28 (DAS28) erythrocyte sedimentation rate (ESR) at 24 and longer weeks.


Secondary Outcome Measures :
  1. Change from baseline ACR20 response rate at 24 and longer weeks. [ Time Frame: Baseline,12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline ACR20 response rate at 24 and longer weeks.

  2. The clinical remission rate at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]

    The percentage of patients who achieve clinical remission patients at the endpoint or withdraw timepoint.

    High disease activity: DAS28 score exceeding 5.1, Moderate disease activity: DAS28 score of exceeding 3.2 to 5.1, Low disease activity (LDA): DAS28 score of less than or equal to 3.2, Remission: DAS28 score is less than 2.6. clinical remission means Low disease activity or remission.


  3. Clinical response was analyzed using the European League Against Rheumatism (EULAR) improvement criteria. [ Time Frame: 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Good response: ΔDAS28 > 1.2 and DAS28 ≤3.2; Moderate response: 1.2 ≥ΔDAS28 > 0.6 and 3.2<DAS28 ≤5.1; or ΔDAS28 > 1.2 and still DAS28>3.2; No response:ΔDAS28≤0.6; or 1.2≥ΔDAS28 > 0.6 and DAS28>5.1。

  4. Change from baseline Simplified Disease Activity Index (SDAI) at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline Simplified Disease Activity Index (SDAI) at 24 and longer weeks.

  5. Change from baseline Clinical disease activity index (CDAI) at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline Clinical disease activity index (CDAI) at 24 and longer weeks.

  6. Change from baseline Erythrocyte Sedimentation Rate (ESR) at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline Erythrocyte Sedimentation Rate (ESR) at 24 and longer weeks.

  7. Change from baseline C-Reactive Protein (CRP) at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline C-Reactive Protein (CRP) at 24 and longer weeks.

  8. Change from baseline swollen joint number (SW28) at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline swollen joint number (SW28) at 24 and longer weeks. SW28 means the number of joints with swelling counted in 28 synovial joints, including proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2) and knees (2) bilateral.

  9. Change from baseline tenderness joint number (T28) at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline tenderness joint number (T28) at 24 and longer weeks. T28 means the number of joints with tenderness upon touching counted in 28 synovial joints, including proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2) and knees (2) bilateral.

  10. Change from baseline patient global assessment(PGA) at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline patient global assessment(PGA) at 24 and longer weeks.

  11. Change from baseline physician global assessment(PHGA) at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline physician global assessment(PHGA) at 24 and longer weeks.

  12. Change from baseline Health Assessment Questionnaire (HAQ) at 24 and longer weeks. [ Time Frame: Baseline, 12 weeks, 24wks,36 wks,48 wks,72 wks,96 wks,120 wks,144 wks ]
    Change from baseline Health Assessment Questionnaire (HAQ) at 24 and longer weeks.

  13. Safety assessed by Adverse Events (AEs) [ Time Frame: Up to 144wks ]
    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product

  14. Safety assessed by incidence of serious adverse events (SAE) [ Time Frame: Up to 144wks ]
    Adverse Event is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02837978


Contacts
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Contact: Qiang Shu, Dr. 0086-0531-82169654 shuqiang@sdu.edu.cn
Contact: Feiying Wang 0086-0531-82169654 375286453@qq.com

Locations
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China, Shandong
Qilu Hospital Recruiting
Jinan, Shandong, China, 250012
Contact: Ming Lv, Prof.    0086-0531-82169166    qlyykyc@163.com   
Sponsors and Collaborators
Qiang Shu
Investigators
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Principal Investigator: Qiang Shu, Dr. Qilu Hospital of Shandong University
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Responsible Party: Qiang Shu, Chief Physician, Qilu Hospital of Shandong University
ClinicalTrials.gov Identifier: NCT02837978    
Other Study ID Numbers: Tacrolimus RA QiluH
First Posted: July 20, 2016    Key Record Dates
Last Update Posted: October 9, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available within 12 months of study completion.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Qiang Shu, Qilu Hospital of Shandong University:
Arthritis, Rheumatoid
Tacrolimus
Treatment outcome
Safety
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Tacrolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Calcineurin Inhibitors