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Risk of Tuberculous and Other Infections in Patients of Spondyloarthritis Treated With Tofacitinib in Bangladesh

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ClinicalTrials.gov Identifier: NCT03504072
Recruitment Status : Recruiting
First Posted : April 20, 2018
Last Update Posted : April 23, 2018
Sponsor:
Information provided by (Responsible Party):
Md. Nazrul Islam, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Brief Summary:

Treatment failure of Spondyloarthropathies (SpA) leads to marked functional disability, higher rates of morbidity, mortality and poor quality of life. In TB endemic countries effective and safe drugs are to be in hand to manage this group of patients. The aim of this study will be to evaluation the risk of tuberculosis and other infections in refractory SpA patients treated with tofacitinib. After having consent 174 adults will be enrolled. Follow up period will be 9 months (visits 0, 1, 3, 6 and 9). Study subjects (87) will receive tofacitinib (5 mg 12 hourly). Control patients will get etanercept (50 mg subcutaneously every 7 days interval for 1st month then 50 mg in 15 days interval for 2nd month then 50 mg every 21 days interval till final visit.

Treatment efficacy assessment tool will be BASDAI, ASDAS-ESR, ASDAS-CRP and ASQoL for quality of life. Occurrences of tuberculosis and serious infection will be the primary end point of this study. The quantitative variables like ESR, CRP, BASDAI, ASDAS-ESR, ASDAS-CRP and ASQoL scores will be computed as mean and SD. Occurrences of TB and infection will be expressed in number and percentage. In between groups according to data distribution, students't test or ManWhitny U test will be done. The P value <0.05 will be considered significant. Each patient will enjoy every right to participate or refuse or even withdraw from the study at any point of time. Anonymity and data confidentiality will be maintained strictly. Ethical clearance will be obtained from Institutional Review Board (IRB) of BSMMU.

The expected utility of this study will be; a) reporting on occurrence of TB and other infections in SpA patients with tofacitinib and etanercept, b) if identified safe and effective physician can use the agents without fear, c) for dose spacing of etanercept the cumulative dose will be low might make the drug affordable and also reduce the risk of TB and other infections, d) for spaced follow up schedule there will be minimized physician visit, lab testing etc.


Condition or disease Intervention/treatment Phase
Spondyloarthritis Drug: Tofacitinib 5 mg, Drug: Etanercept Phase 4

Detailed Description:

Spondyloarthropathies (SpA) are non curable, diseases of young subjects, treatment failure leads to marked functional disability, higher rates of morbidity, mortality and poor quality of life. Effective drugs may not be safe in different geographic backgrounds. Bangladesh is a TB endemic country so patients are at risk of TB and other infections at background. The aim of this study will be to evaluation the risk of tuberculosis and other infections in refractory SpA patients treated with tofacitinib.

In this randomized clinical trial a total 174 adults will be enrolled from BSMMU and other hospitals of Dhaka city. The study period will be from January 2018 to December 2019. Subjects of both gender (≥18 years), who fulfil inclusion criteria will be enrolled after having informed written consent. Follow up period will be 9 months (visits 0, 1, 3, 6 and 9). Study subjects (87) will receive tofacitinib (5 mg 12 hourly). Control patients will get etanercept (50 mg subcutaneously every 7 days interval for 1st month then 50 mg in 15 days interval for 2nd month then 50 mg every 21 days interval till final visit. Demographics, clinical and lab information will be recorded in semi-structured schedule. Treatment efficacy assessment tool will be BASDAI, ASDAS-ESR, ASDAS-CRP and ASQoL for quality of life. Relevant lab test will be done at follow up visits. Side effects will be recorded in the research schedule. Occurrences of tuberculosis and serious infection will be the primary end point of this study. The demographics and categorical outcomes will be expressed in number and percentage. The quantitative variables like ESR, CRP, BASDAI, ASDAS-ESR, ASDAS-CRP and ASQoL scores will be computed as mean and SD. Occurrences of TB and infection will be expressed in number and percentage. Within group the quantitative data of baseline and of final visit will be analyzed using independent sample t test. In between groups according to data distribution, students't test or ManWhitny U test will be done. The P value <0.05 will be considered significant. Each patient will enjoy every right to participate or refuse or even withdraw from the study at any point of time. The study drugs are widely used agents in abroad for different rheumatic conditions having acceptable safety profile with efficacy as such there will be no extra risk of study subjects. Anonymity and data confidentiality will be maintained strictly. Ethical clearance will be obtained from Institutional Review Board (IRB) of BSMMU.

The expected utility of this study will be; a) reporting on occurrence of TB and other infections in SpA patients with tofacitinib and etanercept, b) if identified safe and effective physician can use the agents without fear, c) for dose spacing of etanercept the cumulative dose will be low might make the drug affordable and also reduce the risk of TB and other infections, d) for spaced follow up schedule there will be minimized physician visit, lab testing etc.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Follow up period will be 9 months (visits 0, 1, 3, 6 and 9). Study subjects (87) will receive toficitinib (5 mg 12 hourly). Control patients will get eternacept (50 mg subcutaneously every 7 days interval for 1st month then 50 mg in 15 days interval for 2nd month then 50 mg every 21 days interval till final visit.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Risk of Tuberculosis and Infections in Spondyloarthritis Patients Treated With Tofacitinib in Bangladesh
Actual Study Start Date : January 16, 2018
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Active Comparator: Tofacitinib 5mg
tofacitinib 5 mg 12 hourly daily for 9 months. Evaluation schedule will be baseline, 1st month, 3rd months and 3 monthly for 9 months. relevant investigations will be done at each visit. occurrence of tuberculosis and infections will be recorded at follow up visits.
Drug: Tofacitinib 5 mg,
tofacitinib 5 mg 12 hourly daily for 9 months
Other Name: tofacitinib

Active Comparator: Etanercept 50 mg
Etanercept 50 mg subcutaneously every 7 days interval for 1st month then, Etanercept 50 mg in 15 days interval for 2nd month then 50 mg every 21 days interval for 9 months. Occurrence of tuberculosis and infections will be recorded at follow up visits.
Drug: Etanercept
Etanercept 50 mg sc every 7 days interval in 1st month, every 15 days interval in 2nd month and then every 21 days interval from 3rd month onward upto 9 months
Other Name: Etanercept 50 mg




Primary Outcome Measures :
  1. Occurrence of Tuberculosis [ Time Frame: 9th months ]
    While on trial drug occurrence of tuberculosis either pulmonary or extra pulmonary


Secondary Outcome Measures :
  1. improvement of disease activity measures of spondyloarthritis by >40% [ Time Frame: at 9th month ]

    >40% improvement in at least 4 of the following 5 parameters: Patient global assessment, Pain, Function, Morning stiffness, Spinal mobility, C- reactive protein

    1. Patient global assessment
    2. Pain
    3. Function
    4. Morning stiffness
    5. Spinal mobility C- reactive protein



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. IBP criteria (4 out of 5 parameters present more than 3 months) Inflammatory back pain 1) Age of onset <45 yr 2) Insidious onset 3) Improvement with exercise 4) No improvement with rest 5) Pain at night (with improvement upon arising)
  2. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of > 4 (range, 0-10)
  3. Failing to response to 2 NSAIDs in full therapeutic dose or withdrawal for intolerance in four consecutive weeks
  4. Age > 18 years
  5. Agreed to participate in the study

Exclusion Criteria:

  1. Known case of allergic patients
  2. Pregnancy
  3. Patient with any active or history of any chronic or recurrent or serious or opportunistic infection/sepsis
  4. Known case of chronic kidney disease (Cl cr <40 mL/minute)
  5. Moderate to severe liver disease of any type
  6. Lymphopenia (Lymphocyte <500 cells/mm3 of blood)
  7. Neutropenia (Neutrophil <1000 cells/mm3 of blood)
  8. Anaemia (Hb < 9 g/dl)
  9. Who have been exposed to tuberculosis
  10. Chest X-ray suggestive of pulmonary tuberculosis
  11. Patients who do not want to participate in this study

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): NCT03504072


Contacts
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Contact: Nazrul N Islam, FCPS, MD 8801678112396 islam1nazrul@gmail.com, islam1nazrul@bsmmu.edu.bd
Contact: Nira Ferdous, FCPS 8801816455317 nira1ferdous@gmail.com

Locations
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Bangladesh
Bangabandhu Sheikh Mujib Medical University Recruiting
Dhaka, Bangladesh
Contact: Nazrul Islam, FCPS, MD         
Sponsors and Collaborators
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Investigators
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Study Chair: Shaikh A Al Mamun, MBBS Member secretary

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Responsible Party: Md. Nazrul Islam, Professor, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
ClinicalTrials.gov Identifier: NCT03504072     History of Changes
Other Study ID Numbers: 2018/547
First Posted: April 20, 2018    Key Record Dates
Last Update Posted: April 23, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Md. Nazrul Islam, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh:
Etanercept
Infection
Tofacitinib
Tuberculosis
Spondyloarthritis

Additional relevant MeSH terms:
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Infection
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases
Etanercept
Tofacitinib
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action