Efficacy and Safety of Repeated Intraarticular Injections of Hyaluronic Acid in Patients With OA of the Knee
Primary Purpose
Osteoarthritis of the Knee
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Hyaluronic acid
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis of the Knee
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
hyaluronic acid
Placebo
Arm Description
Cycles of 5 injections of hyaluronic acid at specified intervals
Cycles of 5 injections of saline at specified intervals
Outcomes
Primary Outcome Measures
Responders OARSI 2004 at the End of Follow-up
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
Responders OARSI 2004 at 7 Months Follow-up Visit
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 14 Months Follow-up Visit
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
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.
Responders OARSI 2004 at 27 Months Follow-up Visit
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.
Responders OARSI 2004 at 34 Months Follow-up Visit
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.
Pain or Function Scores Reduction 50% (20mm) at the End of Follow-up
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.
Overall Pain Reduction 20% (10mm) at the End of Follow-up
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.
Function Improvement 20% (10mm) at the End of Follow-up
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.
Patient's Global Assessment Increase 20% (10mm) at the End of Follow-up
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.
Percentage of Patients Who Consumed Rescue Medication for Osteoarthritis
Consumption of rescue medication (paracetamol/NSAID) for osteoarthritis throughout the study, an average of 40 months
Mean Daily Dose of Paracetamol Consumption
Mean daily dose of paracetamol consumption throughout the study, an average of 40 months
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00669032
Brief Title
Efficacy and Safety of Repeated Intraarticular Injections of Hyaluronic Acid in Patients With OA of the Knee
Official Title
Random, Phase IV, Multicentre, Double Blind, Placebo Controlled, Parallel Study to Assess Long-term Efficacy and Safety of Repeated Intraarticular Injections of Hyaluronic Acid (ADANT®) in Patients With Knee OA of the Knee
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
October 2003 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
December 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tedec-Meiji Farma, S.A.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis of the Knee
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
446 (Actual)
8. Arms, Groups, and Interventions
Arm Title
hyaluronic acid
Arm Type
Experimental
Arm Description
Cycles of 5 injections of hyaluronic acid at specified intervals
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Cycles of 5 injections of saline at specified intervals
Intervention Type
Device
Intervention Name(s)
Hyaluronic acid
Intervention Description
3 cycles of 5 hyaluronic acid injections, with a 6 month interval between each one. A 4th treatment cycle of five injections will be carried out at the end of one year
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
3 cycles of 5 saline solution injections, with a 6 month interval between each one. A 4th treatment cycle of five injections will be carried out at the end of one year
Primary Outcome Measure Information:
Title
Responders OARSI 2004 at the End of Follow-up
Description
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.
Time Frame
40 months
Secondary Outcome Measure Information:
Title
Responders OARSI 2004 at 7 Months Follow-up Visit
Description
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.
Time Frame
7 months (6 months after first cycle)
Title
Responders OARSI 2004 at 14 Months Follow-up Visit
Description
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.
Time Frame
14 months (6 months after second cycle)
Title
Responders OARSI 2004 at 21 Months Follow-up Visit
Description
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.
Time Frame
21 months (6 months after third cycle)
Title
Responders OARSI 2004 at 27 Months Follow-up Visit
Description
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.
Time Frame
27 months (12 months after third cycle)
Title
Responders OARSI 2004 at 34 Months Follow-up Visit
Description
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.
Time Frame
34 months (6 months after fourth cycle)
Title
Pain or Function Scores Reduction 50% (20mm) at the End of Follow-up
Description
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.
Time Frame
40 months
Title
Overall Pain Reduction 20% (10mm) at the End of Follow-up
Description
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.
Time Frame
40 months
Title
Function Improvement 20% (10mm) at the End of Follow-up
Description
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.
Time Frame
40 months
Title
Patient's Global Assessment Increase 20% (10mm) at the End of Follow-up
Description
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.
Time Frame
40 months
Title
Percentage of Patients Who Consumed Rescue Medication for Osteoarthritis
Description
Consumption of rescue medication (paracetamol/NSAID) for osteoarthritis throughout the study, an average of 40 months
Time Frame
Throughout the study, an average of 40 months
Title
Mean Daily Dose of Paracetamol Consumption
Description
Mean daily dose of paracetamol consumption throughout the study, an average of 40 months
Time Frame
Throughout the study, an average of 40 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Federico Navarro Sarabia
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
21852252
Citation
Navarro-Sarabia F, Coronel P, Collantes E, Navarro FJ, de la Serna AR, Naranjo A, Gimeno M, Herrero-Beaumont G; AMELIA study group. A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project. Ann Rheum Dis. 2011 Nov;70(11):1957-62. doi: 10.1136/ard.2011.152017. Epub 2011 Aug 17.
Results Reference
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Efficacy and Safety of Repeated Intraarticular Injections of Hyaluronic Acid in Patients With OA of the Knee
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