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临床试验/NCT03122431
NCT03122431已完成4 期

Relevance of Monitoring Blood Levels Compared to Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases: Adherence and Understanding the Possible Underlying Mechanisms Involved in Effectiveness and in Adverse Effects

University of Sao Paulo General Hospital1 个研究点 分布在 1 个国家目标入组 93 人开始时间: 2017年6月5日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
已完成
入组人数
93
试验地点
1
主要终点
Serum Levels of Thalidomide

研究概览

简要总结

No drug treatment is completely free of risk and lack of response, adverse events and poor adherence may affect its effectiveness. Within this context, this project aims to evaluate the importance of monitoring blood levels and salivary drug used in rheumatic autoimmune diseases in the monitoring of adherence to therapy. In addition, this project intends to use the monitoring of drug levels, based on pharmacokinetic studies and pharmacokinetics/pharmacodynamics modeling, to broaden the understanding of the possible cellular, tissue and immunological mechanisms involved in efficacy and adverse effects of these drugs with the prospect of reducing the damage and maintain therapeutic efficacy. The high-performance liquid chromatography (HPLC) coupled to mass spectrometry, which will be used to evaluate hydroxychloroquine, thalidomide, glucocorticoids, is considered the gold standard technology to qualitative and quantitative analysis of drugs in blood and its comparison with the dosage in the saliva is an improvement in simplification of the process. For biological agents the focus will be on the understanding the loss of efficacy and the possible role of anti-TNF antibodies using ELISA capture methodology.This project will be divided into four sections with their respective sub-projects according to the medications that will be studied: hydroxychloroquine, thalidomide, biologic agents and glucocorticoids.

详细描述

No drug treatment is completely free of risk and lack of response, adverse events and poor adherence may affect its effectiveness. There is also a large inter-individual variability in response to treatments with regard to efficacy and toxicity, and for many drugs, there is also a period of weeks to months to establish its efficacy. Within this context, this project aims to evaluate the importance of monitoring blood levels and salivary drug used in rheumatic autoimmune diseases in the monitoring of adherence to therapy. In addition, this project intends to use the monitoring of drug levels, based on pharmacokinetic studies and pharmacokinetics/pharmacodynamics modeling, to broaden the understanding of the possible cellular, tissue and immunological mechanisms involved in efficacy and adverse effects of these drugs with the prospect of reducing the damage and maintain therapeutic efficacy. The high-performance liquid chromatography (HPLC) coupled to mass spectrometry, which will be used to evaluate hydroxychloroquine, thalidomide, glucocorticoids, is considered the gold standard technology to qualitative and quantitative analysis of drugs in blood and its comparison with the dosage in the saliva is an improvement in simplification of the process. The implementation of this methodology dedicated to research in our center, with the necessary training of human resources, will enable the standardization and availability of this advanced technology to other muldisciplinary projects in various areas of science. For biological agents the focus will be on the understanding the loss of efficacy and the possible role of anti-TNF antibodies using ELISA capture methodology.This thematic project will be divided into four sections with their respective sub-projects according to the medications that will be studied: hydroxychloroquine, thalidomide, biologic agents and glucocorticoids.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
None

入排标准

年龄范围
5 Years 至 64 Years(Child, Adult)
性别
All
接受健康志愿者

入选标准

  • SLE diagnosis according to 1997 ACR criteria
  • Active and refractory cutaneous lupus lesions
  • Male gender (using contraceptive barrier method) or confirmed infertility for female gender
  • Normal electroneuromyography at study entry

排除标准

  • Alcoholism
  • History of peripheral neuropathy
  • Previous history of thrombophilia or positive antiphospholipid antibodies
  • Renal and/or central nervous system and/or hematological activity
  • HCQ reduced subproject:
  • Inclusion Criteria:
  • SLE diagnosis according to 1997 ACR criteria
  • Use of hydroxychloroquine (5 to 6.5mg/kg/day) for ≥5 years
  • SLEDAI-2K <4
  • Exclusion Criteria:
  • Alcoholism
  • Renal dialysis
  • Concomitant infectious process
  • Acute and chronic liver diseases
  • Concomitant use of some drugs that interact with HCQ (cimetidine, antacids, digoxin, aminoglycosides, penicillamine, neostigmine, pyridostigmine)
  • Signs of Retinopathy
  • HCQ high subproject:
  • Inclusion Criteria:
  • SLE diagnosis according to 1997 ACR criteria
  • No use of hydroxychloroquine for ≥ 6 months
  • LES/LESJ in activity (SLEDAI≥6)
  • Exclusion Criteria:
  • Alcoholism
  • Renal dialysis
  • Concomitant infectious process
  • Acute and chronic liver diseases
  • Concomitant use of some drugs that interact with HCQ (cimetidine, antacids, digoxin, aminoglycosides, penicillamine, neostigmine, pyridostigmine)
  • Signs of Retinopathy

研究组 & 干预措施

SLE/cutaneous lupus with thalidomide

Other

This subproject includes only one arm of lupus patients with active and refractory cutaneous disease and eligible for Thalidomide 100mg/day for 12 months.

干预措施: Thalidomide (Drug)

Inactive SLE with standard dose of HCQ

Active Comparator

This subproject includes one arm of lupus patients with inactive disease, in which will be maintained on standard dose of Hydroxychloroquine (400mg/day).

干预措施: standard dose of HCQ (Drug)

Inactive SLE with reduced dose of HCQ

Active Comparator

This subproject includes one arm of lupus patients with inactive disease: in which the dose will be reduced to 400mg 3 times a week (Hydroxychloroquine reduced).

干预措施: Hydroxychloroquine reduced (Drug)

结局指标

主要结局

Serum Levels of Thalidomide

时间窗: 12 months

Serum levels of thalidomide by liquid chromatography and tandem mass spectrometry (HPLC-MS/MS)

Serum Levels of Hydroxycloroquine

时间窗: 12 months

Serum levels of hydroxycloroquine by LCMS

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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