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

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.

Study Overview

• Status: Recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Artrodar; Drug: Placebos

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 Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Juree Patarasuwankul; Phone Number: 1308 +66 (0)2 264 20 10; Email: juree.p@trbchemedica.co.th
• Study Contact Backup: Name: Waraporn Sanguanworapong; Phone Number: 1301 +66 (0)2 2642010; Email: waraporn.s@trbchemedica.co.th

Study Locations

• Thailand
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand, 10700
      • Recruiting
      • Siriraj Hospital
      • Contact: Keerati Chareancholvanich, MD.; Phone Number: 66818188568
      • Principal Investigator: Keerati Chareancholvanich, MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: 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
Experimental: diacerein (Artrodar)	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cartilage volume measured by MRI of the affected knee.	Cartilage volume in cc	Change from Day 0 cartilage volume at Day 336, Day 672
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
Rescued medicine consumption		Day 28, Day 84, Day 168, Day 252, Day 336, Day 420, Day 504, Day 588, Day 672
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

Collaborators and Investigators

• Sponsor: TRB Chemedica
• Investigators: Study Director: Nipaporn Jitsook, TRB Chemedica

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2020
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: March 16, 2020
• First Submitted That Met QC Criteria: March 19, 2020
• First Posted (Actual): March 23, 2020

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: DAR-THA-19-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No