Clinical trial NCT04318041: Evaluation of the Structural Modification Effect of Diacerein (Artrodar®) in Knee Osteoarthritic Patients
Official title: Evaluation of the Structural Modification Effect of Diacerein (Artrodar®) in Knee Osteoarthritic Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Knee Osteoarthritis
Lead sponsor: TRB Chemedica
Sponsor class: INDUSTRY
First posted: 2020-03-23
Enrollment: 128
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the structure-modifying effect of Diacerein (Artrodar ®) in knee osteoarthritic (OA) patients by measuring total cartilage volume from magnetic resonance imaging (MRI) of the knee. Half of participants will receive Diacerein (Artrodar ®), while the other half will receive a placebo.

Detailed description: Diacerein (Artrodar ®) participants take 1x1 with evening meal for 1 month (D1-D28) then 1x2 with morning and evening meal for 23 months (D29-end of study). Placebo participants take 1x1 with evening meal for 1 month (D1-D28) then 1x2 with morning and evening meal for 23 months (D29-end of study).

Eligibility criteria: Inclusion Criteria:

1. Patients aged between 40 and 65 years who diagnosed with primary OA knee (medial tibiofemoral compartment) according to ACR criteria
2. Grade II-III OA severity that classified by the Kellgren-Lawrence classification
3. Varus malalignment ≤ 15°
4. Body mass index (BMI) ≤ 30 kg/m2
5. Pain on walking at 15 metres ≥ 30 mm using 100 mm visual analogue pain score (VAPS)
6. Evidence of adequate contraceptive methods in women of childbearing age

Exclusion Criteria:

1. Accompanying osteoarthritis of the hip of sufficient severity to interfere with the functional assessment of the knee
2. Intra-articular treatment with any product (corticosteroids in the last 3 months, glycosaminoglycans, hyaluronic acid in the last 6 months, etc.), joint lavage or arthroscopic procedures within 6 months before the start of the study
3. Oral corticosteroids, oral symptomatic slow acting drug for OA (SYSADOA) treatment (chondroitin sulfate, glucosamine sulfate, piascledin, diacerein) within last 3 months
4. Current treatment with anti-depressants, tranquilisers, antacids or antibiotics
5. Poor general health or other conditions which would make regular hospital attendance difficult
6. Primary inflammatory painful conditions of the knee (e.g. rheumatoid arthritis, psoriatic arthropathy, pseudo-gout)
7. Painful knee conditions other than osteoarthritis (e.g. Sudeck's atrophy, intra-articular neoplasm, villonodular synovitis)
8. Evolving arthritis requiring surgery within the coming year;
9. Persistent diarrhoea (\> 3 stools /24 h) or laxative use (any laxative use is to be stopped before inclusion in the trial)
10. Severe gastrointestinal disorders, indications or history of severe gastrointestinal disorders (e.g. gastric or duodenal ulcers, ulcerative colitis, Crohn's syndrome, diverticulitis, recurrent pancreatitis)
11. Renal insufficiency (estimate glomerular filtration rate ≤ 60 ml/min/1.73 m2)
12. Hepatic disease (transaminases \> 2.5 x upper limit of normal values (ULN) or total bilirubin \> 2 x ULN) or history of alcoholism and liver disease
13. Severe parenchymal organ disease
14. History of heart attack or stroke, or have had serious diseases of the heart such as congestive heart failure, or taking clopidogrel.
15. Patient with diabetes mellitus (DM) who has heamoglobin A1c level \> 8%
16. Patient with hypertension who has systolic blood pressure \> 150 mmHg or diastolic Blood pressure \> 95 mmHg
17. Pregnancy or lactation
18. Participation in a drug clinical trial within the 3 months before the start of the study;
19. Ascertained hypersensitivity to the active ingredient diacerein, to similar compounds, to the excipients or to paracetamol, naproxen, and omeprazole
20. Contraindications for magnetic resonance imaging (MRI) assessment such as heart pacemaker, aneurysm clip or claustrophobia
21. Knee size measured at lower thigh \> 50 cm

Primary outcomes:
measure: Cartilage volume measured by MRI of the affected knee.
timeFrame: Change from Day 0 cartilage volume at Day 336, Day 672
measure: Bone marrow lesions measured by MRI of the affected knee.
timeFrame: Change from Day 0 Bone marrow lesions at Day 336, Day 672
measure: Synovitis measured by MRI of the affected knee.
timeFrame: Change from Day 0 Synovial tissue volume at Day 336, Day 672
measure: Joint space width at narrowest point at medial compartment measured by X-ray (Full extension, weight-bearing position)
timeFrame: Change from Day -7 to -30 Joint space width at Day 168, Day 336, Day 504, Day 672
Secondary outcomes:
measure: Pain at rest
timeFrame: Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
measure: Pain on walking at 15 meters
timeFrame: Day -7 to -30, Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
measure: KOOs
timeFrame: Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
measure: EQ5D5L
timeFrame: Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
measure: Time up-and-go test
timeFrame: Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
measure: Physician and Patient's global assessment
timeFrame: Day 168, Day 336, Day 672
measure: Rescued medicine consumption
timeFrame: Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
measure: Oxford Knee Questionnaire
timeFrame: Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
Other outcomes:
Locations:
city: Bangkoknoi
country: Thailand
facility: Siriraj Hospital
state: Bangkok
Study officials:
affiliation: TRB Chemedica
name: Nipaporn Jitsook
role: STUDY_DIRECTOR
References: