We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Clinical Efficacy and Safety of Leflunomide in Egyptian Patients With Active Rheumatoid Arthritis (CLEAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03599986
Recruitment Status : Completed
First Posted : July 26, 2018
Results First Posted : June 30, 2020
Last Update Posted : June 30, 2020
Sponsor:
Collaborator:
DataClin
Information provided by (Responsible Party):
Adel Mahmoud Elsayed, Eva Pharma

Study Type Observational
Study Design Observational Model: Other;   Time Perspective: Prospective
Condition Active Rheumatoid Arthritis
Enrollment 398
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Single Arm
Hide Arm/Group Description Adult Egyptian patients with active rheumatoid arthritis, fulfilling the ACR/EULAR 2010 classification criteria, for whom leflunomide was prescribed, were included and followed up for 9 months.
Period Title: Overall Study
Started 398
Completed 366
Not Completed 32
Arm/Group Title Single Arm
Hide Arm/Group Description Adult Egyptian patients with active rheumatoid arthritis, fulfilling the ACR/EULAR 2010 classification criteria, for whom leflunomide was prescribed, were included and followed up for 9 months.
Overall Number of Baseline Participants 366
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 365 participants
44.1
(35.78 to 52.42)
[1]
Measure Analysis Population Description: Row population (n=365) differs from the overall population (n=366) due to missing data.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 366 participants
Female
309
  84.4%
Male
57
  15.6%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Patient's distribution per governorates  
Measure Type: Count of Participants
Unit of measure:  Participants
Alexandria Number Analyzed 366 participants
108
  29.5%
Assuit Number Analyzed 366 participants
3
   0.8%
Banha Number Analyzed 366 participants
18
   4.9%
Cairo Number Analyzed 366 participants
98
  26.8%
Ismailia Number Analyzed 366 participants
32
   8.7%
Mansoura Number Analyzed 366 participants
15
   4.1%
Menoufia Number Analyzed 366 participants
27
   7.4%
Minya Number Analyzed 366 participants
17
   4.6%
Zagazig Number Analyzed 366 participants
48
  13.1%
Marital status  
Measure Type: Count of Participants
Unit of measure:  Participants
Single Number Analyzed 366 participants
31
   8.5%
Married Number Analyzed 366 participants
312
  85.2%
Divorced Number Analyzed 366 participants
3
   0.8%
Widow/widower Number Analyzed 366 participants
20
   5.5%
Education  
Measure Type: Count of Participants
Unit of measure:  Participants
Illiterate Number Analyzed 366 participants
31
   8.5%
Basic/primary Number Analyzed 366 participants
80
  21.9%
Secondary Number Analyzed 366 participants
120
  32.8%
University/Higher Number Analyzed 366 participants
135
  36.9%
Residence  
Measure Type: Count of Participants
Unit of measure:  Participants
Rural Number Analyzed 366 participants
138
  37.7%
Urban Number Analyzed 366 participants
228
  62.3%
Birth Control  
Measure Type: Count of Participants
Unit of measure:  Participants
No Number Analyzed 366 participants
151
  41.3%
Yes Number Analyzed 366 participants
135
  36.9%
Missing Number Analyzed 366 participants
80
  21.9%
Specification of birth control method used   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Hormonal Number Analyzed 135 participants
43
  31.9%
Intrauterine Device (IUD) Number Analyzed 135 participants
85
  63.0%
Barrier methods Number Analyzed 135 participants
3
   2.2%
Natural methods Number Analyzed 135 participants
3
   2.2%
Unspecified Number Analyzed 135 participants
1
   0.7%
[1]
Measure Analysis Population Description: The number analyzed (n=135) is that of patients who were using a birth control method during the study period.
Patients currently taking medications for comorbidities  
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 366 participants
101
  27.6%
No Number Analyzed 366 participants
265
  72.4%
Medications for reasons other than Rheumatoid Arthritis  
Measure Type: Count of Participants
Unit of measure:  Participants
Bisporolol Number Analyzed 366 participants
27
   7.4%
Methotrexate Number Analyzed 366 participants
19
   5.2%
Omeprazole Number Analyzed 366 participants
17
   4.6%
Hydrochlorothiazide Number Analyzed 366 participants
16
   4.4%
Diclofenac Number Analyzed 366 participants
14
   3.8%
Folic acid Number Analyzed 366 participants
12
   3.3%
Prednisolone Number Analyzed 366 participants
11
   3.0%
Metformin Number Analyzed 366 participants
10
   2.7%
Glucosamine Number Analyzed 366 participants
9
   2.5%
Pantoprazole Number Analyzed 366 participants
9
   2.5%
Piroxicam Number Analyzed 366 participants
9
   2.5%
Calcium Number Analyzed 366 participants
8
   2.2%
Enalapril maleate Number Analyzed 366 participants
8
   2.2%
Ergocalciferol Number Analyzed 366 participants
8
   2.2%
Chymotrypsin Number Analyzed 366 participants
7
   1.9%
Trypsin Number Analyzed 366 participants
7
   1.9%
Glimepiride Number Analyzed 366 participants
6
   1.6%
Magnesium Number Analyzed 366 participants
6
   1.6%
Calcium carbonate Number Analyzed 366 participants
5
   1.4%
Captopril Number Analyzed 366 participants
5
   1.4%
Diclofenac sodium Number Analyzed 366 participants
5
   1.4%
Pregabalin Number Analyzed 366 participants
5
   1.4%
Vitamin D Number Analyzed 366 participants
5
   1.4%
Atorvastatin Number Analyzed 366 participants
4
   1.1%
Chondroitin sulphate Number Analyzed 366 participants
4
   1.1%
Hydroxychloroquine sulphate Number Analyzed 366 participants
4
   1.1%
Ibuprofen Number Analyzed 366 participants
4
   1.1%
Levothyroxine Number Analyzed 366 participants
4
   1.1%
Meloxicam Number Analyzed 366 participants
4
   1.1%
Ranitidine Number Analyzed 366 participants
4
   1.1%
Silymarin Number Analyzed 366 participants
4
   1.1%
Vitamin B12 Number Analyzed 366 participants
4
   1.1%
Age at first menstrual period   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 244 participants
13
(12 to 14)
[1]
Measure Analysis Population Description: The row population (n=244) differs from that of the overall female population (n=309) because the data of 65 female patients were missing.
Menstruation status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Menstruating Number Analyzed 309 participants
192
  62.1%
Premenopausal Number Analyzed 309 participants
8
   2.6%
Menopausal Number Analyzed 309 participants
38
  12.3%
Post-menopausal Number Analyzed 309 participants
70
  22.7%
Missing Number Analyzed 309 participants
1
   0.3%
[1]
Measure Analysis Population Description: The eligible population for this analysis is the female population (n=309).
Regularity of menstrual periods if menstruating or premenopausal   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Regular Number Analyzed 200 participants
23
  11.5%
Irregular Number Analyzed 200 participants
161
  80.5%
Missing Number Analyzed 200 participants
16
   8.0%
[1]
Measure Description: The regularity of menstrual periods in menstruating patients (n=192) and premenopausal patients (n=8).
[2]
Measure Analysis Population Description: The row population (n=200) is the sum of patients who were menstruating (n=192) and those who were premenopausal (n=8).
Duration of Rheumatoid Arthritis   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 358 participants
2.03
(-0.72 to 4.78)
[1]
Measure Analysis Population Description: The row population (n=358) differs from the overall population (n=366) because the data of 8 patients is missing.
Did the patient receive leflunomide before?  
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 366 participants
51
  13.9%
No Number Analyzed 366 participants
315
  86.1%
Did the patient take a loading dose of leflunomide before?   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 51 participants
31
  60.8%
No Number Analyzed 51 participants
20
  39.2%
[1]
Measure Analysis Population Description: The row population (n=51) differs from the overall population (n=366) because the analysis is concerned with patients who have previously received leflunomide during their past treatment of rheumatoid arthritis.
Duration of RA treatment with medications other than leflunomide   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Months
Number Analyzed 366 participants
27.7
(1.63 to 53.78)
[1]
Measure Description: Duration of treatment of rheumatoid arthritis (RA) with medications other than leflunomide until the time of the first study visit.
AEs/SAEs during previous treatment of RA  
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 366 participants
94
  25.7%
No Number Analyzed 366 participants
252
  68.9%
Missing Number Analyzed 366 participants
20
   5.5%
X-ray performed for both hands?  
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 366 participants
144
  39.3%
No Number Analyzed 366 participants
198
  54.1%
Missing Number Analyzed 366 participants
24
   6.6%
Poor prognostic factors   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Bony erosions by radiograph Number Analyzed 366 participants
90
  24.6%
High swollen joint count Number Analyzed 366 participants
136
  37.2%
Extra-articular disease Number Analyzed 366 participants
19
   5.2%
Functional limitation (HAQ) Number Analyzed 366 participants
240
  65.6%
High disease activity Number Analyzed 366 participants
295
  80.6%
High CRP and ESR or high RF and/or anti-CCP Number Analyzed 366 participants
237
  64.8%
[1]
Measure Description: High disease activity was determined as a measure of composite indices (DAS28, SDAI and/or CDAI).
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram (Kg)
Number Analyzed 348 participants
81.3  (15.25)
[1]
Measure Analysis Population Description: The row population (n=348) is different from the overall population (n=366) given that data on weight is missing from 18 patients.
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Centimeter (cm)
Number Analyzed 346 participants
164  (12.19)
[1]
Measure Analysis Population Description: The number analyzed in row (n=346) differs from the overall population (n=366) because height data is missing from 20 patients.
Heart rate   [1] 
Mean (Standard Deviation)
Unit of measure:  Beats/minute
Number Analyzed 364 participants
81.7  (8.3)
[1]
Measure Analysis Population Description: The row population (n=364) differs from the overall population (n=366) because data on heart rate was missing from 2 patients.
Temperature   [1] 
Mean (Standard Deviation)
Unit of measure:  Degrees Celsius
Number Analyzed 359 participants
37.2  (2.7)
[1]
Measure Analysis Population Description: The row population (n=359) differs from that of the overall population (n=366) because the temperature data of 7 patients were missing.
Systolic blood pressure  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 366 participants
121.9  (13.66)
Diastolic blood pressure   [1] 
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 365 participants
78.36  (7.89)
[1]
Measure Analysis Population Description: Data on diastolic blood pressure is missing from 1 patient.
Physical Examination outcome   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Normal Number Analyzed 359 participants
312
  86.9%
Abnormal Number Analyzed 359 participants
47
  13.1%
[1]
Measure Analysis Population Description: The row population (n=359) differs from the overall population (n=366) because data on physical examination outcome is missing from 7 patients.
Smoking status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Never Number Analyzed 364 participants
333
  91.5%
Former Number Analyzed 364 participants
9
   2.5%
Current Number Analyzed 364 participants
22
   6.0%
[1]
Measure Analysis Population Description: The row population (n=364) is different than that of the overall population (n=366) because data on the smoking status of 2 patients is missing.
Status of alcohol consumption   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Never Number Analyzed 363 participants
363
 100.0%
Yes Number Analyzed 363 participants
0
   0.0%
Missing Number Analyzed 366 participants
3
   0.8%
[1]
Measure Analysis Population Description: The row population (n=363) differs from the overall population (n=366) because data on the status of alcohol consumption is missing from 3 patients.
Patients with comorbidities  
Measure Type: Count of Participants
Unit of measure:  Participants
Yes Number Analyzed 366 participants
115
  31.4%
No Number Analyzed 366 participants
251
  68.6%
Comorbidities  
Measure Type: Count of Participants
Unit of measure:  Participants
Hypertension Number Analyzed 366 participants
60
  16.4%
Atherosclerosis Number Analyzed 366 participants
1
   0.3%
Coronary artery disease Number Analyzed 366 participants
3
   0.8%
Myocardial infarction Number Analyzed 366 participants
1
   0.3%
Stroke Number Analyzed 366 participants
1
   0.3%
Peripheral Vascular Disease Number Analyzed 366 participants
1
   0.3%
Diabetes Mellitus II Number Analyzed 366 participants
21
   5.7%
Obesity Number Analyzed 366 participants
32
   8.7%
Dyslipidemia Number Analyzed 366 participants
10
   2.7%
Respiratory and thoracic disorders Number Analyzed 366 participants
6
   1.6%
GIT disorders Number Analyzed 366 participants
10
   2.7%
Hepatobiliary disorders Number Analyzed 366 participants
1
   0.3%
Nervous system disorders Number Analyzed 366 participants
5
   1.4%
Psychiatric disorders Number Analyzed 366 participants
1
   0.3%
Reproductive system disorders Number Analyzed 366 participants
2
   0.5%
Musculoskeletal disoders Number Analyzed 366 participants
28
   7.7%
Autoimmune disease Number Analyzed 366 participants
10
   2.7%
Other Number Analyzed 366 participants
15
   4.1%
1.Primary Outcome
Title Number of Patients With Remission, Low, Moderate or High Disease Activity (in Terms of CDAI Scores) in Visits 1 and 6.
Hide Description

Assessing the clinical efficacy of leflunomide as first-line therapy and as add-on therapy to other DMARDs, with or without steroids in Egyptian patients with active rheumatoid arthritis [in terms of the number of patients in remission (i.e. CDAI score 0.0 - 2.8), of low disease activity (i.e. CDAI score 2.9 - 10.0), of moderate disease activity (i.e. CDAI score 10.1 - 22.0) and of high disease activity (i.e. CDAI score 22.1 - 76.0) in visits 1 (at baseline) and 6 (at week 36)].

CDAI score: The sum of Tender joint score, Swollen joint score, Patient global score, and Patient global score.

CDAI score interpretation:

0.0 - 2.8: Remission 2.9 - 10.0: Low Activity 10.1 - 22.0: Moderate Activity 22.1 - 76.0: High Activity

Time Frame 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients with at least one treatment dose and post-assessment score of last observation carried forward (LOCF) convention were analyzed in terms of efficacy endpoints.
Arm/Group Title Single Arm
Hide Arm/Group Description:
Adult Egyptian patients with active rheumatoid arthritis, fulfilling the ACR/EULAR 2010 classification criteria, for whom leflunomide was prescribed, were included and followed up for 9 months.
Overall Number of Participants Analyzed 366
Measure Type: Count of Participants
Unit of Measure: Participants
Disease Severity: Remission : Visit 1
0
   0.0%
Disease Severity: Remission : Visit 6
70
  19.1%
Disease severity: Low activity : Visit 1
10
   2.7%
Disease severity: Low activity : Visit 6
116
  31.7%
Disease severity: Moderate activity : Visit 1
53
  14.5%
Disease severity: Moderate activity : Visit 6
113
  30.9%
Disease severity: High activity : Visit 1
303
  82.8%
Disease severity: High activity : Visit 6
67
  18.3%
2.Primary Outcome
Title Number of Patients With Different Disability Scores in Terms of the Mean Relative Change in Health Assessment Questionnaire - Disability Index Score on Visits 1 and 6.
Hide Description

Assessing the clinical efficacy of leflunomide as first-line therapy and as add-on therapy to other DMARDs, with or without steroids in Egyptian patients with active rheumatoid arthritis [in terms of the number of patients with mild difficulties to moderate disability, moderate to severe disability and severe to very severe disability; according to the mean relative change in health assessment questionnaire - disability index score (HAQ-DI) at visits 1 (at baseline) and 6 (at week 36)].

A HAQ-DI score of 0.0 - 1 indicates mild difficulties to moderate disability, a HAQ-DI score of 1.1 - 2 indicates moderate to severe disability and a HAQ-DI score of 2.1 - 3 indicates severe to very severe disability.

There are eight categories; first score within each category: Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities.

Total score is the mean of the eight category scores. Higher scores indicate greater disability.

Time Frame 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:
Adult Egyptian patients with active rheumatoid arthritis, fulfilling the ACR/EULAR 2010 classification criteria, for whom leflunomide was prescribed for 9 months.
Overall Number of Participants Analyzed 366
Measure Type: Count of Participants
Unit of Measure: Participants
HAQ score 0.0 - 1 : Visit 1
112
  30.6%
HAQ score 0.0 - 1 : Visit 6
318
  86.9%
HAQ score 1.1 - 2 : Visit 1
200
  54.6%
HAQ score 1.1 - 2 : Visit 6
43
  11.7%
HAQ score 2.1 - 3 : Visit 1
54
  14.8%
HAQ score 2.1 - 3 : Visit 6
5
   1.4%
3.Secondary Outcome
Title Number of Adverse Events (AEs)/ Serious Adverse Events (SAEs) Experienced by Rheumatoid Arthritis Patients Receiving Leflunomide as First-line Therapy and as add-on Therapy to Other DMARD, With or Without Steroids and Their Relation to Study Medication.
Hide Description Identifying the safety profile of leflunomide whether used as first-line therapy and/or as add-on therapy to other DMARDs with or without steroids in Egyptian patients with active rheumatoid arthritis.
Time Frame 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
In the safety population (n = 398), 23 adverse events were experienced. These are listed in the table.
Arm/Group Title Single Arm
Hide Arm/Group Description:
Adult Egyptian patients with active rheumatoid arthritis, fulfilling the ACR/EULAR 2010 classification criteria, for whom leflunomide was prescribed for 9 months.
Overall Number of Participants Analyzed 398
Measure Type: Count of Participants
Unit of Measure: Participants
Hepatic enzyme increased
6
   1.5%
Swollen/tender joint count increased
2
   0.5%
White blood cell count decreased
2
   0.5%
Abdominal discomfort
2
   0.5%
Cardiac death
1
   0.3%
Anemia
1
   0.3%
Bicytopenia
1
   0.3%
Flushing/hyperhidrosis/dry mouth/lip disoloration
1
   0.3%
Hypertension
1
   0.3%
Oropharyngeal pain
1
   0.3%
Purpura
1
   0.3%
Rheumatoid arthritis
1
   0.3%
Scleritis
1
   0.3%
Supraventricular tachycardia
1
   0.3%
Diarrhea
1
   0.3%
Time Frame Adverse event data were collected between visit 2 (at week 6) and visit 6 (at week 36); making the time frame of collecting safety data 30 weeks.
Adverse Event Reporting Description An adverse event was defined as any untoward medical occurrence in a clinical investigation subject associated with the use of a product or a medical device; the event does not necessarily need to have a causal relationship with the treatment or usage. A serious adverse event was defined as that from clinicaltrials.gov.
 
Arm/Group Title Single Arm
Hide Arm/Group Description Adult Egyptian patients with active rheumatoid arthritis, fulfilling the ACR/EULAR 2010 classification criteria, for whom leflunomide was prescribed, were included and followed up for 9 months.
All-Cause Mortality
Single Arm
Affected / at Risk (%)
Total   0/398 (0.00%) 
Hide Serious Adverse Events
Single Arm
Affected / at Risk (%)
Total   0/398 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Single Arm
Affected / at Risk (%)
Total   20/398 (5.03%) 
Blood and lymphatic system disorders   
White blood cell count decreased   2/398 (0.50%) 
Anemia   1/398 (0.25%) 
Bicytopenia   1/398 (0.25%) 
Cardiac disorders   
Cardiac death   1/398 (0.25%) 
Hypertension   1/398 (0.25%) 
Supraventricular tachycardia   1/398 (0.25%) 
Eye disorders   
Scleritis   1/398 (0.25%) 
Gastrointestinal disorders   
Diarrhea   1/398 (0.25%) 
General disorders   
Abdominal discomfort   2/398 (0.50%) 
Flushing/hyperhidrosis/dry mouth/lip discoloration   1/398 (0.25%) 
Oropharyngeal pain   1/398 (0.25%) 
Hepatobiliary disorders   
Hepatic Enzyme increase   6/398 (1.51%) 
Immune system disorders   
Rheumatoid Arthritis   1/398 (0.25%) 
Musculoskeletal and connective tissue disorders   
Swollen/Tender joint count increased   2/398 (0.50%) 
Skin and subcutaneous tissue disorders   
Purpura   1/398 (0.25%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Writer
Organization: DataClin
Phone: (+2) 01001566602
EMail: mariam.abdalla@dataclin.com
Layout table for additonal information
Responsible Party: Adel Mahmoud Elsayed, Eva Pharma
ClinicalTrials.gov Identifier: NCT03599986    
Other Study ID Numbers: EVA_CLEAR_11022017
First Submitted: January 31, 2018
First Posted: July 26, 2018
Results First Submitted: May 5, 2020
Results First Posted: June 30, 2020
Last Update Posted: June 30, 2020