SLCTR Registration Number
Date of Registration
The date of last modification
Sep 14, 2018
Scientific Title of Trial
Effect of mycophenolate mofetil vs azathioprin on progression of rheumatoid arthritis related interstitial lung disease in patients followed up at the rheumatology clinic, Teaching Hospital Karapitiya – A randomized controlled trial
Public Title of Trial
Effectiveness of mycophenolate mofetil vs azathioprin on progression of rheumatoid arthritis related interstitial lung disease in patients followed up at the rheumatology clinic, Teaching Hospital Karapitiya – a randomized controlled trial
Disease of Health Condition(s) Studied
Rheumatoid arthritis related interstitial lung disease
Universal Trial Number
Any other number(s) assigned to the trial and issuing authority
Ref No. 17.05.2018:3.8 (ERC Ruhuna)
What is the research question being addressed?
What is the effectiveness of mycophenolate mofetil vs azathioprin on progression of rheumatoid arthritis related interstitial lung disease?
Type of study
Randomized controlled trial
Masking not used
Study setting will be outpatient rheumatology clinic, Teaching hospital, Karapitiya
Participants will be subject to base line screening tests including pulmonary function test (Forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO)) and high resolution computerized tomography chest (HRCT) to identify the radiological pattern and to assess the extent of lung fibrosis.
Following basic investigations, participants will be subject to stratified randomization based on gender, predominant HRCT pattern, and lung disease severity.
Permuted block design will be applied to each stratum for 1:1 allocation of two groups.
Route of drug administration will be oral
Mycophenolate mofetil (MMF) treatment group will receive a MMF 250mg bd dosage initially and will be titrated up to 2g/daily or maximum tolerating dose over a period of eight weeks.
Azathioprine treatment group will be given azathioprine 50mg daily at the beginning, increasing up to 2mg/kg or maximum tolerating dose over an eight weeks period.
Both groups will be given prednisolone 0.5mg/kg up to a maximum dose of 25mg for the initial three months period which will be gradually tailed off over a three month period.
This is an open label study. Therefore no one will be blinded.
Patients above 18 years of age
Both male and female
Patients who full fill the American College of Rheumatology (ACR) /European League Against Rheumatism Collaborative initiative (ACR /EULAR) criteria for the diagnosis of rheumatoid arthritis.
Patients with interstitial lung disease, which are diagnosed either based on surgical lung biopsy or radiologically with use of HRCT.
Patients with abnormal diffusing capacity for carbon monoxide (DLCO) and Forced vital capacity (FVC) <85% predicted.
Low disease activity or remission of arthritis, based on disease activity score calculated by using Disease Activity (DAS 28), without treatment of methotrexate or leflunomide three months prior to the screening
Prior use of oral MMF for more than 4 weeks.
Patients with clinical evidence of interstitial lung disease, having other connective tissue disorders other than rheumatoid arthritis
Patients with significant pulmonary pathology on CXR or HRCT, other than interstitial lung disease (eg. lung mass or evidence of active or chronic pulmonary infection).
Patients with pulmonary hypertension requiring specific treatment
patients with evidence of acute infection either in lung or anywhere of the body, whose management would be compromised by either azathioprine or MMF
Patients who are having contraindications or allergic reactions to MMF or azathioprine on previous exposure.
History of persistent leukopenia (white blood cell count < 4000/mm3) or thrombocytopenia (platelet count<100)
Pregnancy (documented by urine pregnancy test) and breast feeding
Smoking of cigars, pipes or cigarettes during the past 6 months.
Absolute change in FVC (expressed in mL) and DLCO from baseline (point of recruitment)
Primary outcome(s) - Time of assessment(s)
At baseline 14 months after initiating of therapy
Change from baseline in diffusing capacity for carbon monoxide (DLCO) at 6 and12 months of treatment initiation.
Change from baseline in Forced Vital Capacity (FVC) at 6 and 12 months of treatment initiation.
Change in 6-minute walk distance after 6 and 12 months of treatment initiation.
Assessment of improvement in quality of life by using SF-36.
Secondary outcome(s) - Time of assessment(s)
At baseline and then at 6 months and 12 months after initiating the treatment
Target number/sample size
70 (35 per arm)
Countries of recruitment
Anticipated start date
Anticipated end date
State of ethics review approval
Approved by the Ethics Review Committee of the Faculty of Medicine, University of Ruhuna on 21.06.2018 (Ref. No.17.05.2018:3.8)
None (Investigator funded)
Contact person for Scientific Queries/Principal Investigator
Dr Kalum Deshapriya
Teaching hospital Karapitiya
Contact Person for Public Queries
Dr. D. P. S. Dissanayake
Senior registrar in Rheumatology
Teaching hospital Karapitiya