Osteoarthrosis
Conditions
Keywords
symptomatic OA of the hand
Brief summary
The goal of the present study is to investigate the effectiveness of Condrosulf® 800 mg tablets vs. placebo once a day for 6 months in the symptomatic treatment of finger joint osteoarthritis. Primary endpoints of the study are the evaluation of global spontaneous pain (Huskisson's Visual Analogue Scale: VAS) and the score of Dreiser's algo-functional index (FIHOA) during the treatment with the tested product, Condrosulf®, versus placebo.
Detailed description
The goal of the present study is to investigate the effectiveness of Condrosulf® 800 mg tablets vs. placebo once a day for 6 months in the symptomatic treatment of finger joint osteoarthritis in 160 randomised patients. Primary endpoints: Primary endpoints of the study are the evaluation of global spontaneous pain (Huskisson's Visual Analogue Scale: VAS) and the score of Dreiser's algo-functional index (FIHOA) during the treatment with the tested product, Condrosulf®, versus placebo. Secondary endpoints are: Efficacy evaluation: Global impression of efficacy expressed by the patient and the physician (VAS), Grip strength (measured manometrically); Morning stiffness duration; Consumption of Paracetamol; Tolerability (4-point verbal scale); Adverse Events occurring during the treatment period; Other parameters:Treatment compliance; Biological markers of arthritis
Interventions
DRUGChondroitin 4&6 sulfate (Condrosulf)
800 mg/day for 6 months
OTHERPlacebo
800 mg placebo/day for 6 months
Sponsors
IBSA Institut Biochimique SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients of either sex * Aged 40 and over * Outpatients * Patients fulfilling the American Congress of Rheumatology (ACR) criteria for the reporting of hand OA * Patients showing X-ray features of hand OA on at least two joints (2 IP and/or 1 IP and 1 TMC) of the dominant hand on standard plain radiographs (\< 6 month). * Suffering from regular spontaneous pain on the dominant hand (VAS \> or = 40 mm at inclusion time). * Showing a FIHOA score \> or = 6. * Having had at least two painful flares in a finger joint during the previous 12 month. * Patients who have signed the written informed consent for their participation in the study * Patients able to understand and follow the protocol. * Patients with a satisfying health and nutritional status. * Female subjects of childbearing potential using, within three months prior to the inclusion in the study, a reliable form of contraception during the course of the study (oral contraceptive pill, intrauterine device or condoms) or female of non childbearing potential (hysterectomy, bilateral ovariectomy or tubal section/ligation). * Female subjects of childbearing potential with a negative urinary pregnancy test before the inclusion in the study.
Exclusion criteria
* Inflammatory joint disease of other origin * Septic arthritis * Chronic inflammatory joint disease * Previous articular fracture of the concerned articulations * Use of analgesic therapy for other indications * Receiving oral corticosteroids * Mono-articular posttraumatic OA of the finger * Planning surgery of the hands in the following 6 months * Patients suffering or having suffered from secondary osteoarthritis after one of the following diseases: * Infectious arthritis - Acromegaly * Ochronosis - Hemachromatosis * Gout - Wilson's disease * Chondrocalcinosis - Paget's disease * Osteochondrosis - Mutation of collagen * Genetic problems (for ex. hypermobility) - Previous joint fracture * Arthropathies of different aetiologies - Algodystrophy (M. Sudeck) * Congenital abnormalities * Recurrent pseudogout * Major dysplasias * Intra-articular injection in a hand joint from less than 3 months * Basic treatment of arthritis with symptom-modifying agents (chondroitin sulfate, glucosamine sulfate, diacerhein, hyaluronic acid) in the last 3 months * Articular lavage in the last 3 months * Treatment with corticoids, by any administration route during the last month * Patient suffering from frequent asthma crises * Physiotherapy, re-education, alternative medicine (mesotherapy, acupuncture) on the hands foreseeable in the next year * Serious organic diseases: heart failure, renal or hepatic insufficiency, blood dyscrasia, serious infection * Participation in other clinical trials in the two months preceding the study * Known or ascertained hypersensitivity to the active ingredient of the tested drug. * Patients refusing to sign the written informed consent form * Patients who do not co-operate, not respecting the protocol requirements * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Global Spontaneous Pain Intensity of Target Hand | 6 months | Intensity of global spontaneous pain is evaluated by the patient himself on a Huskisson's visual analogue scale (VAS) of 100 mm. 0=no pain 100=max pain Change calculated as difference between Month 6 value and baseline value target hand is defined as the patient's most symptomatic hand or, when both hands were equally painful, the patient's dominant hand. |
| Change in Functional Index for Hand Osteoarthritis Dreiser's Score (FIHOA) in the Target Hand | 6 month | Functional Index for Hand Osteoarthritis (Dreiser's Index). Range 0-30 Patients reported the severity of their symptoms by answering a set of 10 questions. Severity was rated on a numerical scale (0 = possible without difficulty, 1 = possible with slight difficulty, 2 =possible with great difficulty, and 3 = impossible), being 30 points the worst possible pain score. Change calculated as difference between the month 6 value and baseline value Target hand defined as the patient's most symptomatic hand or, when both hands were equally painful, the patient's dominant hand |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator Global Evaluation on Efficacy | 6 months | Global impression of the efficacy judged by the Investigators at month 6 by means of a visual analogue scale from 0 (no efficacy) to 100 mm (very good efficacy) |
| Change in Grip Strength | 6 months | Grip strength determined on both hands using a Jamar dynamometer.Patients were required to grip the dynamometer handle and squeeze as hard as possible according to their individual pain limits. The right hand grip was measured first, then the left; this procedure was performed 3 times. The mean value of these 3 measurements was recorded. Change calculated as difference between the month 6 value and baseline value |
| Change in Morning Stiffness Duration | 6 months | Change in morning stiffness duration calculated as the difference between the month 6 value and the baseline value |
| Consumption of Paracetamol | 6 months | Total consumption (between \^baseline and month 6) of paracetamol (500 mg tablets) reported by the patients on a daily diary |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chondroitin 4&6 Sulfate (Condrosulf) Chondroitin 4&6 sulfate (Condrosulf): 800 mg/day for 6 months | 80 |
| Placebo Placebo: 800 mg placebo/day for 6 months | 82 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 8 |
| Overall Study | Change to other therapy | 2 | 1 |
| Overall Study | Intercurrent illness | 1 | 0 |
| Overall Study | Other reasons | 1 | 4 |
| Overall Study | Protocol Violation | 2 | 2 |
Baseline characteristics
| Characteristic | Chondroitin 4&6 Sulfate (Condrosulf) | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 8.5 | 63.5 years STANDARD_DEVIATION 7.9 | 63.0 years STANDARD_DEVIATION 7.2 |
| BMI | 26.7 kg/m^2 STANDARD_DEVIATION 4.5 | 25.9 kg/m^2 STANDARD_DEVIATION 4.2 | 25.0 kg/m^2 STANDARD_DEVIATION 3.8 |
| Functional Index for Hand Osteoarthritis (FIHOA) score, mean +/- SD (standard deviation) | 11.0 units on a scale STANDARD_DEVIATION 4.2 | 10.7 units on a scale STANDARD_DEVIATION 4 | 10.3 units on a scale STANDARD_DEVIATION 3.8 |
| Handedness (no. with dominant left/right hand) left hand | 25 participants | 51 participants | 26 participants |
| Handedness (no. with dominant left/right hand) right hand | 55 participants | 111 participants | 56 participants |
| Handedness (no. with target left/right hand) left hand | 23 participants | 50 participants | 27 participants |
| Handedness (no. with target left/right hand) right hand | 57 participants | 112 participants | 55 participants |
| No. distal interphalangeal (DIP) nodal joints, mean +/- SD (standard deviation), left/right hand left hand | 2.1 number of joints STANDARD_DEVIATION 1.4 | 2.1 number of joints STANDARD_DEVIATION 1.4 | 2.0 number of joints STANDARD_DEVIATION 1.4 |
| No. distal interphalangeal (DIP) nodal joints, mean +/- SD (standard deviation), left/right hand right hand | 2.4 number of joints STANDARD_DEVIATION 1.3 | 2.2 number of joints STANDARD_DEVIATION 1.3 | 2.1 number of joints STANDARD_DEVIATION 1.4 |
| No. of fingers with osteophytes on DIP joints, mean +/- SD (standard deviation), left/right hand left hand | 2.9 number of fingers STANDARD_DEVIATION 1.3 | 3.0 number of fingers STANDARD_DEVIATION 1.2 | 3.0 number of fingers STANDARD_DEVIATION 1.2 |
| No. of fingers with osteophytes on DIP joints, mean +/- SD (standard deviation), left/right hand right hand | 3.1 number of fingers STANDARD_DEVIATION 1.3 | 3.1 number of fingers STANDARD_DEVIATION 1.2 | 3.1 number of fingers STANDARD_DEVIATION 1.1 |
| No. of fingers with osteophytes on PIP joints, mean +/- SD (standard deviation), left/right hand left hand | 1.9 number of fingers STANDARD_DEVIATION 1.6 | 1.9 number of fingers STANDARD_DEVIATION 1.6 | 1.9 number of fingers STANDARD_DEVIATION 1.5 |
| No. of fingers with osteophytes on PIP joints, mean +/- SD (standard deviation), left/right hand right hand | 2.3 number of fingers STANDARD_DEVIATION 1.5 | 2.1 number of fingers STANDARD_DEVIATION 1.5 | 1.9 number of fingers STANDARD_DEVIATION 1.5 |
| No. of painful flares in 12 months, mean +/- SD (standard deviation) | 35.2 flares STANDARD_DEVIATION 80 | 32.6 flares STANDARD_DEVIATION 75.1 | 30.0 flares STANDARD_DEVIATION 70.3 |
| No. of patients with erosive hand OA | 26 participants | 61 participants | 35 participants |
| No. of patients with rhizarthrosis | 37 participants | 80 participants | 43 participants |
| No. of proximal interphalangeal (PIP) nodal joints, mean +/- SD (standard deviation) left/right hand left hand | 1.0 number of joints STANDARD_DEVIATION 1.5 | 0.9 number of joints STANDARD_DEVIATION 1.3 | 0.9 number of joints STANDARD_DEVIATION 1.2 |
| No. of proximal interphalangeal (PIP) nodal joints, mean +/- SD (standard deviation) left/right hand right hand | 1.2 number of joints STANDARD_DEVIATION 1.6 | 1.0 number of joints STANDARD_DEVIATION 1.4 | 1.0 number of joints STANDARD_DEVIATION 1.2 |
| Patient's assess. of global hand pain, mean +/- SD (standard deviation), left/right/target hand left hand | 43.8 mm STANDARD_DEVIATION 21 | 43.1 mm STANDARD_DEVIATION 21.2 | 42.4 mm STANDARD_DEVIATION 21.4 |
| Patient's assess. of global hand pain, mean +/- SD (standard deviation), left/right/target hand right hand | 48.7 mm STANDARD_DEVIATION 19.3 | 47.3 mm STANDARD_DEVIATION 19.2 | 45.9 mm STANDARD_DEVIATION 19.2 |
| Patient's assess. of global hand pain, mean +/- SD (standard deviation), left/right/target hand target hand | 54.9 mm STANDARD_DEVIATION 14.2 | 54.2 mm STANDARD_DEVIATION 14.2 | 53.6 mm STANDARD_DEVIATION 14.2 |
| Region of Enrollment Switzerland | 80 participants | 162 participants | 82 participants |
| Sex: Female, Male Female | 58 Participants | 120 Participants | 62 Participants |
| Sex: Female, Male Male | 22 Participants | 42 Participants | 20 Participants |
| Symptom duration, mean +/- SD (standard deviation) years, left/right hand left hand | 6.9 years STANDARD_DEVIATION 6.3 | 6.5 years STANDARD_DEVIATION 5.8 | 6.2 years STANDARD_DEVIATION 5.3 |
| Symptom duration, mean +/- SD (standard deviation) years, left/right hand right hand | 7.1 years STANDARD_DEVIATION 6.1 | 6.9 years STANDARD_DEVIATION 5.9 | 6.7 years STANDARD_DEVIATION 5.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 82 |
| other Total, other adverse events | 5 / 81 | 4 / 82 |
| serious Total, serious adverse events | 2 / 81 | 2 / 82 |
Outcome results
Primary
Change in Functional Index for Hand Osteoarthritis Dreiser's Score (FIHOA) in the Target Hand
Functional Index for Hand Osteoarthritis (Dreiser's Index). Range 0-30 Patients reported the severity of their symptoms by answering a set of 10 questions. Severity was rated on a numerical scale (0 = possible without difficulty, 1 = possible with slight difficulty, 2 =possible with great difficulty, and 3 = impossible), being 30 points the worst possible pain score. Change calculated as difference between the month 6 value and baseline value Target hand defined as the patient's most symptomatic hand or, when both hands were equally painful, the patient's dominant hand
Time frame: 6 month
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chondroitin 4&6 Sulfate (Condrosulf) | Change in Functional Index for Hand Osteoarthritis Dreiser's Score (FIHOA) in the Target Hand | -2.9 score on a scale | Standard Deviation 5.3 |
| Placebo | Change in Functional Index for Hand Osteoarthritis Dreiser's Score (FIHOA) in the Target Hand | -0.7 score on a scale | Standard Deviation 4.8 |
p-value: 0.008t-test, 2 sided
Primary
Change in Global Spontaneous Pain Intensity of Target Hand
Intensity of global spontaneous pain is evaluated by the patient himself on a Huskisson's visual analogue scale (VAS) of 100 mm. 0=no pain 100=max pain Change calculated as difference between Month 6 value and baseline value target hand is defined as the patient's most symptomatic hand or, when both hands were equally painful, the patient's dominant hand.
Time frame: 6 months
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chondroitin 4&6 Sulfate (Condrosulf) | Change in Global Spontaneous Pain Intensity of Target Hand | -20 mm | Standard Deviation 26 |
| Placebo | Change in Global Spontaneous Pain Intensity of Target Hand | -11.3 mm | Standard Deviation 24 |
p-value: 0.016Wilcoxon (Mann-Whitney)
Secondary
Change in Grip Strength
Grip strength determined on both hands using a Jamar dynamometer.Patients were required to grip the dynamometer handle and squeeze as hard as possible according to their individual pain limits. The right hand grip was measured first, then the left; this procedure was performed 3 times. The mean value of these 3 measurements was recorded. Change calculated as difference between the month 6 value and baseline value
Time frame: 6 months
Population: ITT (missing values were not replaced)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chondroitin 4&6 Sulfate (Condrosulf) | Change in Grip Strength | 2.5 Kg/cm^2 | Standard Deviation 6.6 |
| Placebo | Change in Grip Strength | 0.6 Kg/cm^2 | Standard Deviation 5.8 |
p-value: 0.132Wilcoxon (Mann-Whitney)
Secondary
Change in Morning Stiffness Duration
Change in morning stiffness duration calculated as the difference between the month 6 value and the baseline value
Time frame: 6 months
Population: ITT (missing values were not replaced)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chondroitin 4&6 Sulfate (Condrosulf) | Change in Morning Stiffness Duration | -4.8 minutes | Standard Deviation 16.6 |
| Placebo | Change in Morning Stiffness Duration | 0.3 minutes | Standard Deviation 12 |
p-value: 0.031Wilcoxon (Mann-Whitney)
Secondary
Consumption of Paracetamol
Total consumption (between \^baseline and month 6) of paracetamol (500 mg tablets) reported by the patients on a daily diary
Time frame: 6 months
Population: ITT (missing values were not replaced)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chondroitin 4&6 Sulfate (Condrosulf) | Consumption of Paracetamol | 1.9 tablets/week | Standard Deviation 2.8 |
| Placebo | Consumption of Paracetamol | 2.0 tablets/week | Standard Deviation 4.2 |
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
Investigator Global Evaluation on Efficacy
Global impression of the efficacy judged by the Investigators at month 6 by means of a visual analogue scale from 0 (no efficacy) to 100 mm (very good efficacy)
Time frame: 6 months
Population: ITT (missing values where not replaced)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chondroitin 4&6 Sulfate (Condrosulf) | Investigator Global Evaluation on Efficacy | marked improvement of the clinical condition | 15 Participants |
| Chondroitin 4&6 Sulfate (Condrosulf) | Investigator Global Evaluation on Efficacy | slight improvement of the clinical condition | 20 Participants |
| Chondroitin 4&6 Sulfate (Condrosulf) | Investigator Global Evaluation on Efficacy | doubtful improvement of the clinical condition | 16 Participants |
| Chondroitin 4&6 Sulfate (Condrosulf) | Investigator Global Evaluation on Efficacy | no improvement | 28 Participants |
| Placebo | Investigator Global Evaluation on Efficacy | no improvement | 41 Participants |
| Placebo | Investigator Global Evaluation on Efficacy | marked improvement of the clinical condition | 9 Participants |
| Placebo | Investigator Global Evaluation on Efficacy | doubtful improvement of the clinical condition | 10 Participants |
| Placebo | Investigator Global Evaluation on Efficacy | slight improvement of the clinical condition | 16 Participants |
p-value: 0.043Cochran-Mantel-Haenszel