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

Sponsor
Qiang Shu (Other)
Overall Status
Recruiting
CT.gov ID
NCT02837978
Collaborator
(none)
150
1
2
73
2.1

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Jan 1, 2015
Anticipated Primary Completion Date :
Oct 30, 2020
Anticipated Study Completion Date :
Jan 30, 2021

Arms and Interventions

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 Names:
  • 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 Names:
  • FK506
  • Drug: MTX
    MTX:5mg to 15mg, po, once per week (Qw) until the endpoint or adjusted due to unacceptable toxicity develops.
    Other Names:
  • methotrexate
  • Outcome Measures

    Primary Outcome Measures

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 109 / L, or white blood cell (WBC) <3 x 109 / 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Qilu Hospital Jinan Shandong China 250012

    Sponsors and Collaborators

    • Qiang Shu

    Investigators

    • Principal Investigator: Qiang Shu, Dr., Qilu Hospital of Shandong University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Qiang Shu, Chief Physician, Qilu Hospital of Shandong University
    ClinicalTrials.gov Identifier:
    NCT02837978
    Other Study ID Numbers:
    • Tacrolimus RA QiluH
    First Posted:
    Jul 20, 2016
    Last Update Posted:
    Oct 9, 2020
    Last Verified:
    Oct 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Qiang Shu, Chief Physician, Qilu Hospital of Shandong University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 9, 2020