Efficacy and Safety of Repeated Intraarticular Injections of Hyaluronic Acid in Patients With OA of the Knee

Not Applicable

Completed

Conditions: Osteoarthritis of the Knee

Interventions: Device: Hyaluronic acid
Other: Placebo

Registration Number: NCT00669032

Lead Sponsor: Tedec-Meiji Farma, S.A.

Brief Summary: The main objective is the long-term comparison (3 years and 4 months) of the efficacy and safety of repeated intra-articular administration of hyaluronic acid in the treatment of osteoarthritis of the knee.

Detailed Description: To evaluate the efficacy and safety of repeated injections of hyaluronic acid compared with placebo over a period of 40 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 446

Inclusion Criteria

Patient > 45 years of age
Out-patient diagnosed with primary osteoarthritis of the femorotibial medial joint of the knee with clinical and radiological (Kellgren grade II-III) ACR diagnosis
Joint Space Width (JSW) > 2mm
Overall pain greater or equal to 55mm (VAS - Visual Analogue Scale 100mm) recorded in the knee,by the patient at any time during the week prior to the evaluation

Exclusion Criteria

Overweight patients (body mass index > 32).
Pregnant and lactating women. Women of child-bearinge age not using effective contraception
Patients who have received intra-articular hyaluronic acid within the previous year and/or intra-articular steroids or articular lavage in the chosen knee,within the previous 3 months prior to their inclusion in the study.
AINE administration within the 14 days prior to their inclusion in the study.
Administration of glucosamine sulphate, chondroitin sulphate and diacerein within the 3 months prior to their inclusion in the study.
Immunocompromised patients or patients receiving systemic immunosuppressive therapy.
Patients with known sensitivity to HA, parcetamol or AINEs permitted as rescue medication.
Patients who have received any investigational drug within 30 days prior to visit 1, or who are scheduled for the administration of an investigational drug other than the protocol product during this study.
Patients with severely impaired central nervous system.
Patients with coagulation alterations, despite receiving treatment.
Patients with secondary osteoarthritis of the knee
Patients having previously received surgery, including arthroscopy
Patients with articular inflammatory disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
hyaluronic acid	Hyaluronic acid	Cycles of 5 injections of hyaluronic acid at specified intervals
Placebo	Placebo	Cycles of 5 injections of saline at specified intervals

Primary Outcome Measures

Name	Time	Method
Responders OARSI 2004 at the End of Follow-up	40 months	Percentage of subjects with a clinical response according to Osteaorthritis Research Society International (OARSI) 2004 criteria at the end of follow-up. Patients were classified as responders if the pain or physical function scores decreased at least 50% and at least 20mm on the Visual Analogue Scale (VAS), or if two of the following three findings were recorded: a decrease in pain score of at least 20% or at least 10mm on the VAS, a decrease in physical function score of at least 20% and at least 10mm on the VAS, or an increase in the score of the patient's global assessment by at least 20% and at least 10mm on the VAS. The VAS is set between 0-100mm, higher values represent a worse outcome in all cases except for both patient and physician global assessments where higher values indicate a better outcome.

Secondary Outcome Measures

Name	Time	Method
Responders OARSI 2004 at 27 Months Follow-up Visit	27 months (12 months after third cycle)	Percentage of subjects with a clinical response according to Osteaorthritis Research Society International (OARSI) 2004 criteria at 27 months follow-up visit (12 months after third cycle). Patients were classified as responders if the pain or physical function scores decreased at least 50% and at least 20mm on the Visual Analogue Scale (VAS), or if two of the following three findings were recorded: a decrease in pain score of at least 20% or at least 10mm on the VAS, a decrease in physical function score of at least 20% and at least 10mm on the VAS, or an increase in the score of the patient's global assessment by at least 20% and at least 10mm on the VAS. The VAS is set between 0-100mm, higher values represent a worse outcome in all cases except for both patient and physician global assessments where higher values indicate a better outcome.
Overall Pain Reduction 20% (10mm) at the End of Follow-up	40 months	Percentage of patients with a decrease in pain score of at least 20% or at least 10mm on the VAS at the end of follow-up. The VAS is set between 0-100mm, higher values represent a worse outcome.
Patient's Global Assessment Increase 20% (10mm) at the End of Follow-up	40 months	Percentage of patients with an increase in the score of patient's global assessment by at least 20% and at least 10mm on the VAS at the end of follow-up. The VAS is set between 0-100mm, higher values represent a better outcome.
Responders OARSI 2004 at 7 Months Follow-up Visit	7 months (6 months after first cycle)	Percentage of subjects with a clinical response according to Osteaorthritis Research Society International (OARSI) 2004 criteria at 7 months follow-up visit (6 months after first cycle). Patients were classified as responders if the pain or physical function scores decreased at least 50% and at least 20mm on the Visual Analogue Scale (VAS), or if two of the following three findings were recorded: a decrease in pain score of at least 20% or at least 10mm on the VAS, a decrease in physical function score of at least 20% and at least 10mm on the VAS, or an increase in the score of the patient's global assessment by at least 20% and at least 10mm on the VAS. The VAS is set between 0-100mm, higher values represent a worse outcome in all cases except for both patient and physician global assessments where higher values indicate a better outcome.
Responders OARSI 2004 at 34 Months Follow-up Visit	34 months (6 months after fourth cycle)	Percentage of subjects with a clinical response according to Osteaorthritis Research Society International (OARSI) 2004 criteria at 34 months follow-up visit (6 months after fourth cycle). Patients were classified as responders if the pain or physical function scores decreased at least 50% and at least 20mm on the Visual Analogue Scale (VAS), or if two of the following three findings were recorded: a decrease in pain score of at least 20% or at least 10mm on the VAS, a decrease in physical function score of at least 20% and at least 10mm on the VAS, or an increase in the score of the patient's global assessment by at least 20% and at least 10mm on the VAS. The VAS is set between 0-100mm, higher values represent a worse outcome in all cases except for both patient and physician global assessments where higher values indicate a better outcome.
Responders OARSI 2004 at 14 Months Follow-up Visit	14 months (6 months after second cycle)	Percentage of subjects with a clinical response according to Osteaorthritis Research Society International (OARSI) 2004 criteria at 14 months follow-up visit (6 months after second cycle). Patients were classified as responders if the pain or physical function scores decreased at least 50% and at least 20mm on the Visual Analogue Scale (VAS), or if two of the following three findings were recorded: a decrease in pain score of at least 20% or at least 10mm on the VAS, a decrease in physical function score of at least 20% and at least 10mm on the VAS, or an increase in the score of the patient's global assessment by at least 20% and at least 10mm on the VAS. The VAS is set between 0-100mm, higher values represent a worse outcome in all cases except for both patient and physician global assessments where higher values indicate a better outcome.
Responders OARSI 2004 at 21 Months Follow-up Visit	21 months (6 months after third cycle)	Percentage of subjects with a clinical response according to Osteaorthritis Research Society International (OARSI) 2004 criteria at 21 months follow-up visit (6 months after third cycle). Patients were classified as responders if the pain or physical function scores decreased at least 50% and at least 20mm on the Visual Analogue Scale (VAS), or if two of the following three findings were recorded: a decrease in pain score of at least 20% or at least 10mm on the VAS, a decrease in physical function score of at least 20% and at least 10mm on the VAS, or an increase in the score of the patient's global assessment by at least 20% and at least 10mm on the VAS. The VAS is set between 0-100mm, higher values represent a worse outcome in all cases except for both patient and physician global assessments where higher values indicate a better outcome.
Pain or Function Scores Reduction 50% (20mm) at the End of Follow-up	40 months	Percentage of patients with a decrease in pain or physical function score of at least 50% and at least 20mm on the VAS at the end of follow-up. The VAS is set between 0-100mm, higher values represent a worse outcome.
Function Improvement 20% (10mm) at the End of Follow-up	40 months	Percentage of patients with a decrease in physical function score of at least 20% or at least 10mm on the VAS at the end of follow-up. The VAS is set between 0-100mm, higher values represent a worse outcome.
Percentage of Patients Who Consumed Rescue Medication for Osteoarthritis	Throughout the study, an average of 40 months	Consumption of rescue medication (paracetamol/NSAID) for osteoarthritis throughout the study, an average of 40 months
Mean Daily Dose of Paracetamol Consumption	Throughout the study, an average of 40 months	Mean daily dose of paracetamol consumption throughout the study, an average of 40 months