Clinical trial NCT02930343
Conditions: Rheumatoid Arthritis
Sponsor: Jawaharlal Institute of Postgraduate Medical Education & Research
Start date: 2016-09-01; Completion date: 2018-08-01
Enrollment: 136 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RA (Rheuatoid arthritis) is a multisystem disease that mainly involves joints resulting in destructive arthritis if not treated rapidly. Inspite of various advances in field of early diagnosis and treatment of RA, there is still a need for better understanding of the efficacy and safety of various combinations of conventional DMARDS, and to rank them in order accordingly, so as to give a clearer vision for further management of RA once MTX monotherapy fails, so as to achieve remission as soon as possible. The study will be conducted at the Department of Clinical Immunology, JIPMER (Jawaharlal Institute of Postgraduate Medical Education \& Research). patients who fail methotrexate monotherapy will be randomised to 2 treatment arms - either a combination of Sulfasalazine (SSZ), Hydroxychloroquine (HCQ) and Methotrexate (MTX) or Leflunomide (LEF), Hydroxychloroquine (HCQ) and Methotrexate (MTX)

Detailed description:
Patients aged ≥18 years, fulfilling the 2010 ACR EULAR criteria for RA (symptom duration less than two years) , having more than 4 joints involved \& having moderate to severe disease activity (DAS28≥3.2) will be invited to participate. After providing written informed consent, eligible patients will be first started on MTX monotherapy \& only patients who have persistant moderate disease activity (DAS28 ESR \> 3.2) will be randomized into two groups. Block randomization will be done to generate random allocation sequence

Group 1 - will receive MTX+LEF+HCQ Group 2- will receive MTX+SSZ+HCQ

DMARD dosages used are: MTX 25 mg/week orally (dosage after 6 weeks),SSZ 2g/d (after 4 weeks) LEF 20 mg/day (dosage after 2 weeks) and HCQ 200 mg/day. Glucocorticoids will be given in an oral tapering scheme. All patients will be prescribed folic acid (10 mg/week) during MTX prescription.

Arms: arm 1: Active Comparator: Combination of Methotrexate (up to 25 mg per week), Leflunomide (20 mg once a day) and Hydroxychloroquine (200-400 mg once at night). All drugs are to be taken orally. Duration of therapy is for 3 months. All patients will receive folic acid (5 mg twice a week) along with methotrexate. Low dose prednisolone (weeks 1-2: 7.5 mg/day, weeks 2-4: 5 mg/day, weeks 4-6: 5 mg on alternate day and then stop) will be given as bridging therapy. arm 2: Combination of Methotrexate (up to 25 mg per week), Sulfasalazine (2g per day) and Hydroxychloroquine (200-400 mg once at night). All drugs are to be taken orally. Duration of therapy is for 3 months. All patients will receive folic acid (5 mg twice a week) along with methotrexate. Low dose prednisolone (weeks 1-2: 7.5 mg/day, weeks 2-4: 5 mg/day, weeks 4-6: 5 mg on alternate day and then stop) will be given as bridging therapy.
Interventions: intervention 1: Methotrexate intervention 2: Leflunomide intervention 3: Hydroxychloroquine intervention 4: Prednisolone intervention 5: Folic Acid intervention 6: Sulfasalazine
Intervention descriptions: intervention 1: Methotrexate, a structural analogue of folic acid, can be administered orally or parenterally to treat a variety of rheumatic diseases intervention 2: Leflunomide inhibits pyrimidine synthesis, resulting in blockade of T-cell proliferation. Leflunomide is used in patients with moderate to severe active rheumatoid arthritis with early or late disease intervention 3: Hydroxychloroquine (HCQ) is a well-tolerated DMARD that is commonly used in combination therapy regimens for RA. HCQ is more commonly used than chloroquine. intervention 4: Low dose prednisolone (weeks 1-2: 7.5 mg/day, weeks 2-4: 5 mg/day, weeks 4-6: 5 mg on alternate day and then stop) intervention 5: Folic acid is to be given to all patients receiving methotrexate at a dose of 5 mg twice a week. intervention 6: 5-aminosalicylic acid (5-ASA) is the active component of sulfasalazine; the specific mechanism of action of 5-ASA is unknown; however, it is thought that it modulates local chemical mediators of the inflammatory response, especially leukotrienes, and is also postulated to be a free radical scavenger or an inhibitor of tumor necrosis factor (TNF)

Protocol documents:
Prot_SAP_ICF_000.pdf: 
1 
 
                                             COVERING LETTER 
From: 
Pooja J Belani 
Principal Investigator. 
Jawaharlal Institute of Postgraduate Medical Education & Research. 
23.02.2021 
 
To, 
Clinicaltrial.gov. 
 
Subject : Submission of Study protocol, Statistical analysis plan (SAP) and 
informed consent form (ICF) . 
 
Dear Sir// Madam, 
I, Pooja Belani, am hereby submitting study protocol, statistical analysis plan 
(SAP) and informed consent form (ICF) for the following clinical study (details): 
 
Study Title : Comparison of Sulfasalazine versus Leflunomide based combination disease 
modifying anti-rheumatic drug therapy (DMARD) in patients with Rheumatoid 
arthritis failing Methotrexate monotherapy : A randomized control trial 
NCT number : NCT02930343 
Document date : 02.05.2016 
 
Kindly find appropriate documents hereby . 
Thanking you. 
Best regards. 
 
 
 
 
 
 
 
 
 
 
 
 


2 
 
STUDY PROTOCOL 
 
Background 
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammatory 
polyarthritis. The hallmark of RA is symmetric synovial proliferation and inflammation of joints 
that leads to erosions and progressive destruction of joints leading to disability. Disease 
modifying anti rheumatic drugs (DMARDS) form the mainstay for RA treatment. Early 
aggressive treatment of RA can halt or slow down the disease progression and disease, thus 
decreasing disease related disability and improving the quality of life significantly. 
 
The current strategy for treatment of RA is “treat – to- target” approach (1) to achieve early and 
sustained remission. Methotrexate is the initial drug of choice for early DMARD naïve patients. 
Patients not achieving the target for disease control, can be started either on combination of 
conventional DMARDS therapy or biologic agents (TNF inhibitors) (1)(2). According to the latest 
EULAR recommendations, addition of a biological DMARD, especially a Tumor Necrosis Factor 
(TNF) inhibitor, should be considered when poor prognostic factors are present; in the absence 
of poor prognostic factors, a combination therapy should be considered. (2).  
 
The main hurdle for the use of TNF inhibitors or other biologicals for management of RA in 
Indian as well as western setting is high cost of therapy.  The annual cost for biologic treatment 
for RA ranges from Rs. 3 lacs (for Rituximab) to Rs. 44 lacs ( for Adalimumab), whereas that 
for combination therapy with Methotrexate (MTX) + Sulfasalazine (SSZ) + Hydroxychloroquine 
(HCQ) is Rs.15,000 and that of MTX+ Leflunomide (LEF)+HCQ is Rs. 30,000. Also the rate of 
infections with Biologics is higher especially Tuberculosis in Indian setting. The combination 
non-biological DMARDs are not only cheaper but also safer alternatives to the biological agents. 
 
However, there are no guidelines to direct the treating physician regarding the choice of 
combination conventional DMARDs as there are no head to head trials comparing the efficacy, 
safety and cost effectiveness of various combination DMARDs. 
 
Rationale 
Inspite of various advances in field of early diagnosis of RA, there is still a need for better 
understanding of the efficacy and safety of various combinations of conventional DMARDS, and 
to rank them in order accordingly, so as to give a clearer vision for further management of RA 
once MTX monotherapy fails, and to achieve remission as soon as possible. 
 
Novelty 


3 
 
This study will attempt to compare 2 different DMARD combinations (MTX+SSZ+HCQ versus 
MTX+LEF+HCQ) in terms of its efficacy and safety in the treatment of  RA.. Both these regimes 
are approved and used for the treatment of RA but head to head comparison data is not 
available. 
 
Expected outcome and application 
The results of the study may help to rationalize treatment of patients with RA especially in 
countries like India where resources are limited and cost is a constraint. The result of the study 
may also provide evidence for better and prompt management of the disease with appropriate 
combination therapy once MTX monotherapy fails. 
 
Research Question: which combination of conventional DMARD is better and should be 
recommended, in terms of efficacy and safety for the treatment of early RA, in patients who fail 
to respond to Methotrexate monotherapy? 
 
Research Hypothesis: LEF based combination DMARD regimes is inferior to SSZ based 
combination DMARD therapy in safety and efficacy in patients with RA who fail initial MTX 
monotherapy. 
Aims and Objectives: (PICO format)  
Aim : To compare 2 combination DMARD therapies (MTX+SSZ+HCQ versus MTX+LEF+HCQ) 
in patient with early RA who have failed MTX monotherapy 
Objectives :  
1. To assess safety and efficacy of MTX+LEF+HCQ based combination DMARD therapy 
in patients with early RA failing MTX monotherapy 
2. To assess safety and efficacy of MTX+SSZ+HCQ based combination DMARD therapy 
in patients with early RA failing MTX monotherapy 
3. To compare the safety and efficacy profile of 2 combination DMARD therapy 
(MTX+LEF+HCQ and MTX+SSZ+HCQ) 
 
 
Methodology 
A. Study design/type:  Randomized  parallel group non-inferiority trial, pragmatic 
design 
B. Study participants:  Humans 
 
For Participants 
a. Inclusion criteria   :  


4 
 
Age >18 years satisfying ACR-EULAR criteria for RA 
1. Polyarthritis (>4 joints) 
2. Disease duration of less than 2 years                 
3. Patients with moderate to severe disease activity (DAS28>3.2) 
4. Patients who have failed to respond to initial Methotrexate monotherapy 
 
b. Exclusion criteria   : 
1. End stage disease (deformed fixed joints) 
2. Patients with vasculitis, extra-articular features like interstitial lung disease 
3. Contraindications to DMARD therapy (Chronic Alcoholism, Chronic liver 
disease, Evidence of acute/chronic infection, Chronic kidney disease, 
Patients with leucopenia (<3.0×109/l), thrombocytopenia (<150×109/l), 
AST/ALT>2× upper normal value and creatinine clearance <30ml/minute ) 
4. Pregnant, lactating women ; patients (both men and women) of reproductive 
age group unwilling for contraceptive use who have not completed the family 
5. Patients unable to come for regular follow up 
 
c. Number of groups to be studied, their names and definitions: 
Group 1: MTX+LEF+HCQ 
Group 2: MTX+SSZ+HCQ 
C. Sampling                                                                   
a. Sampling Population         : Patients >18 years of age diagnosed with RA, 
attending OPD services of  the Department of Clinical Immunology 
b. Sample size calculation      :  (calculated for non inferiority trial) 
Sample size has been estimated as 70 patients in each group using the N master 
software considering success rate as 75 % in both groups ( calculated from FIN-
RACo trial group, Lancet 1999 (13) ) and non inferiority limit as 20% with 5 % alpha 
error ,statistical power of 80 % and dropout rate as 20% 
c. Sampling technique: 
block randomization 
D. Randomization details: block of 10, 1:1 random allocation. 
E. Study Procedure  
A. Selection of participants: All consecutive patients of RA attending the OPD services of 
the department of Clinical Immunology will be included to reach a minimum sample 
size of in each group.  
B. Patients will be assessed for eligibility and will be started on Methotrexate monotherapy 
initially and then only patients, who have moderate to severe disease activity inspite of 
12 weeks of Methotrexate monotherapy, will be randomized to either of the 2 groups of 
DMARDs. 


5 
 
C. Allocation to groups:  
Allocation concealment will be done by : Sequentially numbered, opaque, sealed 
envelopes (SNOSE) method 
Group 1: MTX+LEF+HCQ  
Group 2: MTX+SSZ+HCQ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All consecutive patients of RA attending 
the OPD services of the department of 
Clinical Immunology  
Excluded  (n=   ) 
   Not meeting inclusion criteria (n=  ) 
   Declined to participate (n=  ) 
   Other reasons (n=  ) 
Analysed  at the end of 12 weeks and 24 
weeks (n=  ) 
 Excluded from analysis (give reasons) (n=  ) 
Lost to follow-up (give reasons) (n=  ) 
Discontinued intervention (give reasons) (n=  ) 
Allocated to MTX+LEF+HCQ (n= 70 ) 
 Received allocated intervention (n=  ) 
 Did not receive allocated intervention (give 
reasons) (n=  ) 
Lost to follow-up (give reasons) (n=  ) 
Discontinued intervention (give reasons) (n=  ) 
Allocated to MTX+SSZ+HCQ (n= 70 ) 
 Received allocated intervention (n=  ) 
 Did not receive allocated intervention (give 
reasons) (n=  ) 
Analysed at the end of 12 weeks and 24 
weeks (n=  ) 
 Excluded from analysis (give reasons) (n=  ) 
Allocation
Analysis
Follow-Up
Randomized (n= 140 ) 
Enrollment
Eligible patients  
Methotrexate monotherapy 
Assess disease activity at end of 12 weeks 
DAS 28 ESR ≥3.2 


7 
 
 
F. Data Collection method including settings and periodicity: Patients aged above 18 
years diagnosed as RA according to the 2010ACR-EULAR criteria will be screened 
and evaluated for inclusion in the study. The patients will be examined every 2 week 
interval during DMARD dose escalation & then every month for next 6 weeks of 
MTX and for 24 weeks for either groups. 
a. Clinical evaluation: 
i. Adverse drug reactions (ADRs) – each visit 
ii. IHAQ, DAS28 - once at baseline and then at 12 weeks of MTX 
monotherapy and then at the end of 24 weeks treatment with either 
of Group 1 or group 2 drug. 
 
b. Laboratory: 
i. Routine CBC/RFT/LFT: every 2 week interval during dose 
escalation & then every month for 12 weeks after starting the drug 
ii. ESR & hsCRP for disease activity evaluation: every month. 
iii. USG wrist, hand and feet (US-7 score)- at baseline and at 12 
weeks of Group 1 or group 2 drug 
 
G. List of variables and their measurement methods with standardization techniques: 
a. (i)  Independent variables                             
Socio-demographic profile: 
 
Age 
 
Gender 
b. Outcome Variables: 
Disease-related parameters –  
Primary outcome measures: 
a. Disease activity (state) - DAS28  
Secondary outcome measures: 
a. Functional ability – iHAQ 
b. Mean changes over time in: 
i. Inflammatory parameters: ESR, hs-CRP  
ii. Disease activity as per US-7 score 
c. Adverse drug reactions 
 
 
 
 


8 
 
Primary endpoint: 
 
 
 
Proportion of patients in both groups achieving good response according to  
European League Against Rheumatism (EULAR) response criteria at the end of 12 weeks of 
combination therapy 
 
Secondary endpoint: 
1. Change in functional ability (Indian Health Assessment Questionnaire; iHAQ) at the 
end of 12 weeks of combination therapy 
2. disease activity by US7 score at 12 weeks 
3. Safety of study medications (adverse drug reactions) during study period (till 24 
weeks) 
4. Proportion of patients achieving good EULAR response at the end of 24 weeks of 
combination therapy 
 
 
Assessment of treatment response 
The disease activity will be reassessed at the end of 12 and 24 weeks of random group 
allocation. The treatment response will be graded according to EULAR response criteria 
 
Radiological assessment of disease activity 
Musculoskeletal Ultrasound (US-7 score) will be performed in all patients in non blinded 
manner by the researcher 
 
Clinical Evaluation :  
a. Demography: Age/Sex, ethnicity 
b. Detailed history and examination will be done for all patients 
c. Baseline evaluation of patient 
Disease Activity: Indian Health associated questionnaire (IHAQ), Disease 
Activity Score-28 (DAS28) 
Damage: Joint: Loss of motion, Deformity, Mal-alignment 
d. Extra-articular: Sicca symptoms & signs, sub cutaneous nodules, evidence of 
Interstitial Lung Disease (ILD), peripheral neuropathy, scleritis/episcleritis 
Laboratory investigations 
i. Routine: Complete blood count (CBC), Erythrocyte Sedimentation Rate 
(ESR), Sugar (FBS/PP2BS), Liver Function Test (LFT), Renal function test 
(RFT), Mantoux Test, Viral markers (HIV, HBsAg, Anti HCV), urine 
analysis, Thyroid function test (TFT) 


9 
 
ii. Ultrasound (USG) wrist, hand and feet (US-7 score) 
Immunological: High sensitivity C-reactive protein (hsCRP), Rheumatoid Factor 
(RF), Anti-CCP antibody (ACPA) in all participants .  
 
After baseline evaluation, all consecutive patients with RA will be started on MTX 
monotherapy unless contraindicated. Patients not responding adequately to MTX 
monotherapy (DAS28>3.2) at the end of 12 weeks will be randomized to either of the 2 
groups by block randomization after written informed consent. 
 
MTX+LEF+HCQ- Group 1 
 
MTX+SSZ+HCQ- Group 2 
Concurrent treatment with the following drugs will be allowed during the study as per 
severity of symptoms and in cases of breakthrough pain: 
1. Non-steroidal anti-inflammatory drugs (NSAIDs) - Tablet Diclofenac sodium 50mg 
twice a day (will be given for minimum duration) and if given on “as and when 
required” basis, patient will be asked to maintain an NSAID dairy so as to know 
their requirement. 
2. Oral low dose Glucocorticoids (GC) - 7.5 mg/d for 4 weeks followed by 5 mg/day 
for 2 weeks followed by 5mg on alternate day for 2 weeks – as a bridge therapy. 
Thereafter, it can be given if disease flares (patient being symptomatic with 
continued DMARD therapy), with the maximum dose being 7.5mg/day. 
3. Intra articular steroids-will be allowed during the study, as per severity of patient’s 
symptoms. The number of intraarticular injections required in each group will be 
calculated. 
DMARD dosages used are:  
For all patients as a standard protocol for management of all patients with RA : 
1. MTX – starting dose 10 mg/week orally for 2 weeks         15mg / week for 2 weeks            
20 mg/ week for 2 weeks            25mg/ week            assessment of response to 
MTX after 6 weeks (at the end of 12 weeks after starting MTX) 
2. In patients , not tolerating adequate doses of oral MTX in the form of nausea, 
vomiting, the following strategies will be adopted- 1) dose will be split into two 2) 
oral MTX will be converted to im formulation. 
3. T. Ondansetron 4mg twice a day for 2 days a week will be allowed in the study 
if patient has nausea or vomiting with MTX. 
4. T. Folic acid 5 mg twice a week 
Those not achieving adequate response to a maximum permissible dose of  MTX (25 mg / 
week) ie. DAS28ESR >3.2 will be enrolled in the study after randomization: 
 


10 
 
For Group 1 
1. T. MTX will be continued at 25mg/week 
2. T. folic acid 5 mg twice per week 
3. T. LEF -10 mg/day starting dose for 2 weeks             20mg /day 
4. T. HCQ 200 mg/day at night 
For Group 2 
1. T.MTX will be continued at 25mg/week 
2. T. Folic acid 5 mg twice a week 
3. T.SSZ 500mg once a day for 7 days            500mg twice a day for 7 days           
500mg thrice a day for 7 days             1gram twice a day 
4. T. HCQ 200mg/day at night 
Note: During the course of the study any patients developing extra-articular manifestations 
requiring different mode of therapy will be excluded from study (but intention to treat analysis 
will be used for analysis of results). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


11 
 
STATISTICAL ANALYSIS PLAN (SAP) 
The trial is designed as a non-inferiority pragmatic trial trial. The assessment will 
be done in unblinded fashion by the researcher. Arbitrarily considering EULAR 
good response rate (primary endpoint) of 75% with SSZ based triple regimen 
(tREACH and TICORA study) and non-inferiority margin of ∆=(-20%) for LEF, a 
sample size of 140 (70 in each group) was determined using nMaster sample size 
calculator (version2 software) using 2-sided confidence levels (CI) of 95%, power 
of 80% and dropout rate of 20%. 
 
Data will be analyzed using SPSS (IBM pasw statistics, version 19.0) for windows. 
For quantitative data [DAS28ESR, iHAQ], normality of distribution will be checked 
by Shapiro-Wilks W test. Continuous data was presented as median and interquartile 
range (IQR25-75) / mean with SD as appropriate . Mann-Whitney U test / Students 
t test will be used for comparison between median/ mean of 2 groups respectively. 
Qualitative or categorical variables (such as EULAR good response) will be 
described as proportions and will be tested using Chi-square. Odds ratio (OR) – odds 
of achieving the outcome (treatment response) in patients exposed to LEF in 
comparison to patients not exposed to LEF (SSZ group) along with 95% confidence 
interval and p-value will be used to study the statistically significant difference in 
treatment outcome between 2 groups. P-value of <0.05 was considered as 
significant. 
 
The primary endpoint will be analyzed by both intention-to-treat (ITT) and per-
protocol (PP) analysis. The rest of the parameters will be analyzed by ITT analysis 
only. Patients who do not complete the study, the last observation will be taken as 
their outcome for ITT analysis. For missing data, the last available readings will be 
carried forward in case of patients who are not available for the endpoint assessment. 
Non-inferiority testing will be done by using a 95% confidence interval (CI) of the 
difference between the proportions of patients achieving the primary endpoint 
between 2 groups. Extension of CONSORT 2010 statement will be used for 
reporting of non-inferiority of the LEF group.  
              
 
 
 
 
 
 
 
 
 


12 
 
INFORMED CONSENT FORM 
(ICF) 
Patient / Participant information sheet 
INFORMATION FOR PARTICIPANTS OF THE STUDY 
 
Title of the project:  Comparison of Sulfasalazine versus Leflunomide based combination 
Disease modifying anti rheumatic drug (DMARD) therapy in patients 
with Rheumatoid arthritis failing Methotrexate monotherapy : A 
randomized control trial 
 
Purpose of this project/study 
This comparative study will help us determine which combination of drugs used for the treatment 
of rheumatoid arthritis called as DMARDs is safer and more effective in patients who have failed 
to respond adequately to treatment with a single drug methotrexate. 
 
Procedure/methods of the study 
The study will be conducted at the Department of Clinical Immunology, JIPMER. Once you are 
diagnosed to have RA with the disease duration of less than 2 years, you will be evaluated for 
disease activity and severity, socio-demographic features, extra-articular manifestations. You 
will be evaluated for your suitability to be treated DMARDs by a battery of blood and radiological 
tests. All testing will be done inside hospital, free of cost. The results of the investigation will be 
made available and discussed with you. You will be informed about the nature and severity of 
the disease and about the various treatment options and the duration of treatment.  During the 
course of treatment you will be regularly evaluated for beneficial as well as adverse effect of the 
drugs.  On completion of the study if you have satisfactory response, you will continue to receive 
the drugs. Otherwise other suitable modality of treatment as per standard guidelines will be 
offered. 
Expected duration of the subject participation: 
24 weeks 
 
The benefits to be expected from the research to the participant or to others and the post 
trial responsibilities of the investigator 
In early RA, once patient fails the initial 12 weeks trial of MTX monotherapy, the patient is at a 
very high risk of joint deformities and disability. At present there is no consensus or any definite 
guidelines to guide the treating physician for the next step of management. Combination drugs 
(DMARDs) or Biologics are recommended as the next line of management. However, biologics 
are very costly (more than 100 times the cost of combination drugs) and out of the reach of 
most of Indian population. Therefore the most suitable option is combination DMARD therapy. 


13 
 
However, as of now we do not know which combination is better for the management of severe 
RA nonresponsive to methotrexate. This study takes that initiative to compare the efficacy and 
safety of the two easily available and cheap combination DMARDs for the treatment of 
rheumatoid arthritis. Thus, the results of the study may be beneficial to the participant as well 
as other patients of rheumatoid arthritis. 
 
Any risks expected from the study to the participant 
The study is trying to find out the best combinations of drugs for the treatment of patients with 
severe rheumatoid arthritis who do not respond to methotrexate. The drugs used for the 
treatment are the approved ones for the treatment of this condition and will be used according 
to standard guidelines for treatment of RA. Rarely these drugs may be associated with side 
effects which in most cases are minor and can be prevented from happening by your regular 
follow up clinical and laboratory evaluation. The treatment does not contain any additional 
procedure or treatment other than the standard of care practice for the management of RA. 
Therefore there are no additional risks to the patient other than expected during the normal 
course of treatment of patients with RA.  
 
Maintenance of confidentiality of records 
Yes. The information obtained from you will be maintained confidential. In case of   publication 
of data the individual identities of the study participants will not be disclosed. Your identity will 
be maintained confidential during all the steps of the study i.e. data collection, analysis and 
publication. 
 
Provision of free treatment for research related injury 
The study procedure carries more than minimal risk. In the case of research related injury free 
treatment will be provided as per JIPMER guidelines.  
 
Compensation for participating in the study  
Participation in the study is voluntary without any financial incentives 
 
Compensation to the participants for foreseeable risks and unforeseeable risks related 
to research study leading to disability or death. 
Compensation for any unforeseeable events, disability and death will be paid as per JIPMER 
guidelines. 
 
Freedom to withdraw from the study at any time during the study period without the 
loss of benefits that the participant would otherwise be entitled9 
Yes, you can, at your own discretion, withdraw from the study at any time without assigning 


14 
 
any reasons and without loss of benefits. Withdrawal from the study will not affect your 
regular treatment in the hospital in any way. 
 
Possible current and future uses of the biological material and of the data to be generated 
from the research and if the material is likely to be used for secondary purposes or would 
be shared with others 
Biologic materials (serum) will be used for patient investigations only and will not be used for 
any other purposes. Records will be preserved for a period of 3 years. Data emerging from this 
study may be published as a research article in medical research journals without divulging 
individual identities of the study participants. Biological materials will not be shared with others. 
Address and telephone number of the investigator and co-investigator/guide 
 
  
Signature of the investigator:  
 
Signature and thumb imprint of participant : 
 
Signature and thumb imprint of witness : 
 
 Date: _____________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


15 
 
CONSENT FORM 
 
Title of the project: Comparison of Sulfasalazine versus Leflunomide based combination 
disease modifying anti rheumatic drug (DMARD) therapy in patients with Rheumatoid arthritis 
failing Methotrexate monotherapy: A randomized control trial 
 
Participant’s name:                           Address: 
 
 
 
 
The details of the study have been provided to me in writing and explained to me in my 
own language. I confirm that I have understood the above study and had the opportunity to ask 
questions. I understand that my participation in the study is voluntary and that I am free to 
withdraw at any time, without giving any reason, without the medical care that will normally be 
provided by the hospital being affected. Risk-benefit of the study has been explained to me. I 
agree not to restrict the use of any data or results that arise from this study provided such a use 
is only for scientific purpose(s). I have been given an information sheet giving details of the 
study. I fully consent to participate in the above study.  
 
 
 
 
Signature of the participant: ______________________ Date: _____________ 
 
 
 
 
Signature of the witness: ________________________ Date: _____________ 
 
 
Name: 
Address: 
 
 
Signature of the investigator: ________________________ Date: _____________ 
 
 
 


16 
 
 
 
DATA COLLECTION PROFORMA 
CODE NO:                               
 
 
 
 
Date of enrollment: 
 
Name/ age/ sex/ CCR no : 
 
 
 
 
      Contact number  
  
Disease duration: 
 
 
 
 
 
 
Co-morbid conditions (with duration): 
Personal history (habits/addictions): 
Treatment history: 
Family history: 
Baseline Investigations: 
RF: 
 
 
 
 
 
HIV: 
 
HBsAg: 
HCV: 
Anti-CCP: 
 
 
 
 
Mantoux test: 
 
Drug   
 
Dose  
 
since when 
 
 
Side effects 
1 
 
2 
 
3 
 
Baseline 
4mo 
5mo 
6mo 
IA Steroids 
 
 
 
 
Oral steroids 
 
 
 
 
 
 
Baseline
4 week 
8 week 
12 week
16 week
20 week 
24 week 
TJ28 
 
 
 
 
 
 
 
SJ28 
 
 
 
 
 
 
 
VAS 
 
 
 
 
 
 
 
ESR 
 
 
 
 
 
 
 
hsCRP 
 
 
 
 
 
 
 
DAS28 
 
 
 
 
 
 
 
iHAQ 
 
 
 
 
 
 
 
Morning 
stiffness 
 
 
 
 
 
 
 


17 
 
 
FOLLOW UP INVESTIGATIONS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Extraarticular 
features 
 
 
 
 
 
 
 
Adverse drug 
reactions 
 
 
 
 
 
 
 
Investigations 
Baseline
4W
8W
12W
16W
20W
24W
Hb 
 
 
 
 
 
 
 
TLC 
 
 
 
 
 
 
 
DLC 
 
 
 
 
 
 
 
MCV 
 
 
 
 
 
 
 
Platelets 
 
 
 
 
 
 
 
Peripheral smear
 
 
 
 
 
 
 
Urine albumin 
 
 
 
 
 
 
 
Microscopy 
 
 
 
 
 
 
 
Blood urea 
 
 
 
 
 
 
 
Sr. Creatinine 
 
 
 
 
 
 
 
Bilirubin (T/D) 
 
 
 
 
 
 
 
AST/ ALT 
 
 
 
 
 
 
 
ALP/GGT 
 
 
 
 
 
 
 
Total protein /Alb
 
 
 
 
 
 
 
CPK / LDH 
 
 
 
 
 
 
 
Sugar (AC/PC) 
 
 
 
 
 
 
 
CH/TG/HDL/LDL 
 
 
 
 
 
 
 
CT/USG/MRI 
 
 
 
 
 
 
 
ECG/ECHO 
 
 
 
 
 
 
 


18 
 
 
US7 Score 
 
Baseline 
12 week 
24 week 
Synovitis  
GS 
 
 
 
PD 
TS 
GS 
 
 
 
PD 
Erosion 
GS