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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 -

SLCTR Registration Number

SLCTR/2018/031


Date of Registration

14 Sep 2018

The date of last modification

Sep 14, 2018



Application Summary


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


Scientific Acronym

None


Public Acronym

None


Brief title

None


Universal Trail Number

U1111-1216-0731


Any other number(s) assigned to the trial and issuing authority

Ref No. 17.05.2018:3.8 (ERC Ruhuna)


Trial Details


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

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Masking not used


Control

Standard therapy


Assignment

Parallel


Purpose

Treatment


Intervention(s) planned

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.


Inclusion criteria

  1. Patients above 18 years of age

  2. Both male and female

  3. 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.

  4. Patients with interstitial lung disease, which are diagnosed either based on surgical lung biopsy or radiologically with use of HRCT.

  5. Patients with abnormal diffusing capacity for carbon monoxide (DLCO) and Forced vital capacity (FVC) <85% predicted.

  6. 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


Exclusion criteria

  1. Prior use of oral MMF for more than 4 weeks.

  2. Patients with clinical evidence of interstitial lung disease, having other connective tissue disorders other than rheumatoid arthritis

  3. 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).

  4. Patients with pulmonary hypertension requiring specific treatment

  5. patients with evidence of acute infection either in lung or anywhere of the body, whose management would be compromised by either azathioprine or MMF

  6. Patients who are having contraindications or allergic reactions to MMF or azathioprine on previous exposure.

  7. History of persistent leukopenia (white blood cell count < 4000/mm3) or thrombocytopenia (platelet count<100)

  8. Pregnancy (documented by urine pregnancy test) and breast feeding

  9. Smoking of cigars, pipes or cigarettes during the past 6 months.



Primary outcome(s)

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


Secondary outcome

  1. Change from baseline in diffusing capacity for carbon monoxide (DLCO) at 6 and12 months of treatment initiation.

  2. Change from baseline in Forced Vital Capacity (FVC) at 6 and 12 months of treatment initiation.

  3. Change in 6-minute walk distance after 6 and 12 months of treatment initiation.

  4. Assessment of improvement in quality of life by using SF-36.


Secondary outcome(s) - Time of assessment(s)

  1. Change from baseline in diffusing capacity for carbon monoxide (DLCO) at 6 and12 months of treatment initiation.

  2. Change from baseline in Forced Vital Capacity (FVC) at 6 and 12 months of treatment initiation.

  3. Change in 6-minute walk distance after 6 and 12 months of treatment initiation.

  4. Assessment of improvement in quality of life by using SF-36.



Target number/sample size

70 (35 per arm)


Countries of recruitment

Sri Lanka


Anticipated start date

2018-09-17


Anticipated end date

2019-10-01


Recruitment status

Pending


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)


Funding source

None (Investigator funded)



Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr Kalum Deshapriya
Consultant Rheumatologist
Teaching hospital Karapitiya

Mob: 0772619674

kalumdeshapriya@hotmail.com

Contact Person for Public Queries

Dr. D. P. S. Dissanayake
Senior registrar in Rheumatology
Teaching hospital Karapitiya
0912232250
0777757583

dissanayakesajeewani@yahoo.com


Primary study sponsor/organization

Teaching Hospital Karapitiya

Karapitiya, Galle, Sri Lanka
Tel: 091-2232250, 091-2232251
Fax: 091 2232268

Secondary study sponsor (If any)

None