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

Knee Osteoarthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04318041
• Other study ID #: DAR-THA-19-01
• Status: Recruiting
• Phase: Phase 3
• Start date: November 22, 2020
• Est. completion date: October 2024

Study information

• Verified date: October 2023
• Source: TRB Chemedica
• Contact: Juree Patarasuwankul
• Phone: +66 (0)2 264 20 10
• Email: juree.p[@]trbchemedica.co.th
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 128
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Artrodar
Diacerein (Artrodar): D1-D28 (1 month): Artrodar (50 mg) 1 x 1 with evening meal D29-end of study (23 months): Artrodar (50 mg) 1 x 2 with meal
• Placebos
Placebo: D1-D28 (1 month): Placebo 1 x 1 with evening meal D29-end of study (23 months) Placebo 1 x 2 with meal

Locations

Country	Name	City	State
Thailand	Siriraj Hospital	Bangkoknoi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
TRB Chemedica

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cartilage volume measured by MRI of the affected knee.	Cartilage volume in cc	Change from Day 0 cartilage volume at Day 336, Day 672
Primary	Bone marrow lesions measured by MRI of the affected knee.	Bone marrow lesions in mm3	Change from Day 0 Bone marrow lesions at Day 336, Day 672
Primary	Synovitis measured by MRI of the affected knee.	Synovial tissue volume in mm3	Change from Day 0 Synovial tissue volume at Day 336, Day 672
Primary	Joint space width at narrowest point at medial compartment measured by X-ray (Full extension, weight-bearing position)	Joint space width in mm	Change from Day -7 to -30 Joint space width at Day 168, Day 336, Day 504, Day 672
Secondary	Pain at rest	Visual analogue scale (VAS) 0-100 mm. 0 is no pain, 100 is extreme pain.	Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
Secondary	Pain on walking at 15 meters	Visual analogue scale (VAS) 0-100 mm. 0 is no pain, 100 is extreme pain.	Day -7 to -30, Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
Secondary	KOOs	Knee and Osteoarthritis Outcome Score from 1-5 Likert scale score with higher scores denoting worse pain and disability.	Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
Secondary	EQ5D5L	EQ5D5L is a standardized instrument for measuring generic health status	Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
Secondary	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
Secondary	Physician and Patient's global assessment	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.	Day 168, Day 336, Day 672
Secondary	Rescued medicine consumption		Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
Secondary	Oxford Knee Questionnaire	1-5 Likert scale score with higher scores denoting worse pain and disability.	Day 0, Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672