Evaluation of the Structural Modification Effect of Diacerein (Artrodar®) in Knee Osteoarthritic Patients

Phase 3

Recruiting

• Conditions: Knee Osteoarthritis
• Interventions: Drug: Artrodar; Drug: Placebos

• Registration Number: NCT04318041
• Lead Sponsor: TRB Chemedica

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).

Study Timeline

• Study First Submitted: 2020-03-16
• Study First Submitted QC: 2020-03-19
• Study First Posted: 2020-03-23
• Study Start: 2020-11-22
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-20
• Last Update Posted: 2024-11-22
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 128

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
diacerein (Artrodar)	Artrodar	-
placebo	Placebos	-

Primary Outcome Measures

Name	Time	Method
Synovitis measured by MRI of the affected knee.	Change from Day 0 Synovial tissue volume at Day 336, Day 672	Synovial tissue volume in mm3
Cartilage volume measured by MRI of the affected knee.	Change from Day 0 cartilage volume at Day 336, Day 672	Cartilage volume in cc
Bone marrow lesions measured by MRI of the affected knee.	Change from Day 0 Bone marrow lesions at Day 336, Day 672	Bone marrow lesions in mm3
Joint space width at narrowest point at medial compartment measured by X-ray (Full extension, weight-bearing position)	Change from Day -7 to -30 Joint space width at Day 168, Day 336, Day 504, Day 672	Joint space width in mm

Secondary Outcome Measures

Name	Time	Method
Physician and Patient's global assessment	Day 168, Day 336, Day 672	Visual analogue scale (VAS) 0-100 mm to assess efficacy and tolerability by physician and patient. 0 is not effective/ no tolerate, 100 is very effective/ very good.
Rescued medicine consumption	Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
Pain at rest	Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672	Visual analogue scale (VAS) 0-100 mm. 0 is no pain, 100 is extreme pain.
Oxford Knee Questionnaire	Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672	1-5 Likert scale score with higher scores denoting worse pain and disability.
Pain on walking at 15 meters	Day -7 to -30, Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672	Visual analogue scale (VAS) 0-100 mm. 0 is no pain, 100 is extreme pain.
KOOs	Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672	Knee and Osteoarthritis Outcome Score from 1-5 Likert scale score with higher scores denoting worse pain and disability.
EQ5D5L	Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672	EQ5D5L is a standardized instrument for measuring generic health status
Time up-and-go test	Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672

Trial Locations

Locations (1)

Siriraj Hospital; 🇹🇭 Bangkoknoi, Bangkok, Thailand