Condrosulf vs Celebrex vs Placebo in the Treatment of Knee OA

A Multicentre, Comparative, Randomised, Double-blind, Double-dummy Clinical Trial on the Efficacy and Safety of Condrosulf Versus Celebrex and Versus a Placebo in the Treatment of Knee Osteoarthritis

The purpose of this study is to confirm the efficacy and safety of 800 mg Chondroitin 4&6 sulfate (Condrosulf) vs placebo once a day for 6 months in the symptomatic treatment of knee osteoarthritis. A third group, Celecoxib 200 mg (Celebrex) once a day, will be used as active comparator.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: placebo; Drug: celecoxib; Drug: chondroitin sulfate

• Study Type: Interventional
• Enrollment (Actual): 604
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Liege, Belgium, 4020
    • Unité d'exploration du metabolism osseux, CHU, Polyclinique universitaires L-Brull
• Czech Republic
  • Breclav, Czech Republic
    • Interni a revmatologicka ordinace
  • Brno, Czech Republic
    • Ortopedicka Ambulance
  • Ostrava, Czech Republic
    • Vesalion s.r.o.
  • Praha - Krc, Czech Republic
    • Thomayerova nemocnice - Revmatologicke a rehabilitacne oddeleni
  • Praha 2, Czech Republic
    • Revmatologicky Ustav
  • Uherske Hradiste, Czech Republic
    • Medical Plus
• Italy
  • Firenze, Italy
    • Azienda Osp. Univ. Di Careggi
• Poland
  • Lodz, Poland
    • Klinika Zdrowej Kości
  • Swidnik, Poland
    • Lubelskie Centrum Diagnostyczne
  • Warszawa, Poland
    • Medica Pro Familia
  • Wiejska, Poland
    • Zdrowie Osteo-Medic
  • ul. Jana III Sobieskiego, Poland
    • SOLB
• Switzerland
  • Basel, Switzerland
    • Bethesda-Spital
  • Fribourg, Switzerland
    • HFR Fribourg - Hôpital Cantonal
  • Zürich, Switzerland
    • Universitätsspital Zürich, Rheumaklinik

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatients of either sex, aged ≥50 years
• Patients affected by primary knee osteoarthritis of the medial or lateral femoro-tibial compartment
• Diagnosis according to the American College of Rheumatology (ACR) criteria
• Kellgren & Lawrence grade I-III
• Knee osteoarthritis evolving for more than 6 months
• Patients suffering from regular pain and functional disorders from at least 3 months
• Accomplishing a score ≥ 7 of Lequesne's index for the knee osteoarthritis
• Assessing pain on Huskisson's VAS ≥ 50 mm
• With radiography dated less than six months showing a remaining articular joint space
• Without such an axial disorder to justify an osteotomy
• Women taking contraceptive measures if not in menopause
• Women having negative pregnancy test
• Patients able to understand and follow the study protocol
• Patients who have signed the written informed consent for their participation in the clinical trial

Exclusion Criteria:

• With a history of heart attack, ischemic heart disease or cerebrovascular disease (including transient ischemic attacks)
• Having or have had peripheral arterial disease or past surgery orf peripheral arteries
• With a history or currently significat coagulation defect or/and blood dyscrasia
• With high risk of cardiovascular events
• With any acute or chronic infections requiring antimicrobial therapy or serious viral (e.g., hepatitis, HIV positivity) or fungal infections
• With a history of recurrent gastrointestinal ulceration or active inflammatory bowel diseases (e.g., Crohn's disease or ulcerative colitis)
• Having been diagnosed as having or have been treated for oesophageal, gastric, pyloric channel, or duodenal ulceration within 30 days prior to receiving the first dose of study medication
• Having severe liver or kidney disease
• With allergy to Celebrex or any of the other ingredients of Celebrex
• Having had an allergic reaction to sulphonamides
• Having had, as a result of intake of acetylsalicylic acid or other NSAIDs, asthma, nose polyps, severe nose congestion, or an allergic reaction such as itchy skin rash, swelling of the face, lips, tongue or throat, breathing difficulties or wheezing
• Presenting lactose intolerance
• Mild or not symptomatic knee osteoarthritis : < 7 of Lequesne's index,
• Pain on Huskisson's VAS (Visual Analogic Scale) < 50 mm
• Predominantly femoro-patellar osteoarthritis
• Destructive osteoarthritis of the knee justifying a surgery in the following 6 months
• Osteoarthritis with hydrarthrosis requiring a puncture or an infiltration
• Important genu varum or valgus >8° (physiological angle including)
• Kellgren & Lawrence grade IV
• Knee joint surgery in the last 3 months (e.g. chondroscopy, arthroscopy)
• Viscosupplementation, tidal lavage in the last 6 months
• Arthritis and metabolic arthropathies, Paget's illness
• Having consumed: basic treatment of arthritis with SYSADOA, symptomatic slow acting drugs for osteoarthrithis (chondroitin sulphates, glucosamine sulphates, diacerhein, hyaluronic acid and food supplement for joint care) in the last 3 months; treatment with corticoids, by any administration route during the last month; any medication having an influence on pain:
• NSAIDs (nonsteroidal anti-inflammatory drugs) in the 5 days preceding the inclusion (wash-out period considering 5 half-lives of the drug)
• hypnotics, muscle relaxants, anxiolytics, if the intake has started less than 8 days before inclusion
• paracetamol in the 10 hours preceding the inclusion
• Foreseen physiotherapy, re-education, alternative medicine (mesotherapy, acupuncture) in the next six months (study period)
• Presenting psychiatric illness hindering the protocol complaince, alcoholism, ongoing or < 1 year drug dependency
• Pregnant or likely to become it during clinical trial or lactating
• Women having positive pregnancy test
• Having participated in other clinical trials in the month preceding the clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Condrosulf (Chondroitin 4&6 sulfate); 1 tablet of Condrosulf 800 mg and 1 capsule of placebo of Celebrex once a day for 182 days	Drug: chondroitin sulfate; Other Names: Condrosulf
Placebo Comparator: Placebo (PBO) 800 mg tablet and Placebo (PBO) 200 mg capsule; 1 tablet of PBO of Condrosulf and 1 capsule of PBO of Celebrex, once a day for 182 days	Drug: placebo; Other Names: placebo for chondroitin sulfate and placebo for celecoxib
Active Comparator: Celebrex 200 mg capsule; 1 capsule of 200 mg of Celebrex and 1 tablet of 800 mg placebo of Condrosulf once a day for 182 days	Drug: celecoxib; Other Names: Celebrex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lequesne's Index	Decrease in the scores of the Lequesne's Index from Day 1 to Day 182.	Day 1 and Day 182
Pain (VAS in mm)	Decrease in the VAS (pain in mm) from Day 1 to Day 182	Day 1 and Day 182

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lequesne's Index	Evolution from Day 1 to Day 30, Day 90 and Day 182	Day 1, 30, 90 and 182
Pain (VAS in mm)	Evolution of the pain on VAS (in mm) from Day 1 to Day 30, Day 91 and Day 182	Day 1, 30, 91 and 182
MCII (minimal clinically important improvement)		Day 1, 30, 91 and 182
PASS (patient acceptable symptom state)		Day 1, 30, 91 and 182
Consumption of Paracetamol		Day 1, 30, 91 and 182
Global efficacy assessment	Global efficacy assessed by the patient and the Investigator by means of a semi-quantitative verbal scale.	At Day 30, 91 and 182
Number of adverse events related to the treatments		At Day 30, 91 and 182
Number of drop-outs due to AE (adverse event) related to the treatment		At Day 30, 91 and 182

Other Outcome Measures

Outcome Measure	Time Frame
Treatment compliance	Day 1, 30, 91 and 182

Collaborators and Investigators

• Sponsor: IBSA Institut Biochimique SA
• Investigators: Principal Investigator: Jean-Yves Reginster, Prof. MD PhD, Unité d'Exploration du Métabolisme Osseux, CHU Centre ville, Polycliniques Universitaires L-Brull, Liège, Belgium

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2014
• Primary Completion (Actual): October 19, 2015
• Study Completion (Actual): June 16, 2016

Study Registration Dates

• First Submitted: February 28, 2014
• First Submitted That Met QC Criteria: March 4, 2014
• First Posted (Estimate): March 6, 2014

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: March 1, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Knee osteoarthritis; Chondroitin sulfate; Celebrex; Condrosulf; Knee OA
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: 12EU/Ct06; 2013-001619-62 (EudraCT Number)