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Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases

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ClinicalTrials.gov Identifier: NCT03122431
Recruitment Status : Recruiting
First Posted : April 20, 2017
Last Update Posted : September 14, 2020
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
University of Sao Paulo General Hospital

Tracking Information
First Submitted Date  ICMJE April 17, 2017
First Posted Date  ICMJE April 20, 2017
Last Update Posted Date September 14, 2020
Actual Study Start Date  ICMJE June 5, 2017
Actual Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2017)
  • Serum levels of thalidomide [ Time Frame: 30 days, 3 months, 6 months and 12 months ]
    Improvement of Cutaneous Lupus Area and Severity Activity Index Score (CLASI)
  • Serum levels of hydroxycloroquine - HCQ reduced [ Time Frame: 6 months, 12 months and 24 months ]
    Disease flare evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K)
  • Serum levels of hydroxycloroquine - HCQ high [ Time Frame: 3 months ]
    Disease flare evaluated by Systemic Lupus Erythematosus Disease Activity Index
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This study includes 3 subprojects that will assess serum drug levels for efficacy and toxicity. In the first two subprojects, hydroxychloroquine will be studied in SLE population. In the third subproject, thalidomide and SLE and cutaneous lupus will be studied.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Systemic Lupus Erythematosus (SLE)
  • Juvenile SLE
  • Cutaneous Lupus
Intervention  ICMJE
  • Drug: Thalidomide
    Thalidomide 100mg/day
    Other Name: Thalidomide 100 MG
  • Drug: Hydroxychloroquine reduced
    Hydroxychloroquine 400mg three times a week
    Other Name: HCQ reduced
  • Drug: Hydroxychloroquine high
    Hydroxychloroquine 800mg/day for three months
    Other Name: HCQ high
Study Arms  ICMJE
  • SLE/cutaneous lupus with thalidomide
    This subproject includes only one arm of lupus patients with active and refractory cutaneous disease and eligible for Thalidomide 100mg/day for 12 months.
    Intervention: Drug: Thalidomide
  • No Intervention: Inactive SLE with standard dose of HCQ
    This subproject includes 2 arms of lupus patients with inactive disease: one group will be maintained on standard dose of Hydroxychloroquine (400mg/day) and in the other, the dose will be reduced to 400mg 3 times a week for two years.
  • Active Comparator: Inactive SLE with reduced dose of HCQ
    This subproject includes 2 arms of lupus patients with inactive disease: one group will be maintained on standard dose of Hydroxychloroquine (400mg/day) for two years and in the other, the dose will be reduced to 400mg 3 times a week (Hydroxychloroquine reduced) for two years.
    Intervention: Drug: Hydroxychloroquine reduced
  • Experimental: Active SLE with initial high dose of HCQ
    This subproject includes 2 arms of lupus patients with active disease: one group will be started on standard dose of Hydroxychloroquine (400mg/day) for two years and in the other, the dose will be started at high dose 800mg/day (Hydroxychloroquine high) for three months.
    Intervention: Drug: Hydroxychloroquine high
  • No Intervention: Active SLE with standard dose of HCQ
    This subproject includes 2 arms of lupus patients with active disease: one group will be started on standard dose of Hydroxychloroquine (400mg/day) for three months and in the other, the dose will be started at high dose 800mg/day (Hydroxychloroquine high) for three months.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 17, 2017)
296
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 5, 2022
Actual Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Thalidomide subproject:

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 64 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eloisa Bonfa, MD, PhD 55 11 30617490 eloisa.bonfa@hc.fm.usp.br
Contact: Clovis Silva, MD, PhD 55 11 26618563 clovisaasilva@gmail.com
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03122431
Other Study ID Numbers  ICMJE HPLC-Rheumatic diseases
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Sao Paulo General Hospital
Study Sponsor  ICMJE University of Sao Paulo General Hospital
Collaborators  ICMJE Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators  ICMJE
Principal Investigator: Eloisa Bonfa, MD, PhD University of Sao Paulo
PRS Account University of Sao Paulo General Hospital
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP