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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
Tedec-Meiji Farma, S.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoarthritis of the Knee

Eligibility Criteria

45 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    First Posted
    April 25, 2008
    Last Updated
    August 2, 2023
    Sponsor
    Tedec-Meiji Farma, S.A.
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    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
    result

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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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