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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tedec-Meiji Farma, S.A.
ClinicalTrials.gov Identifier:
NCT00669032
First received: April 25, 2008
Last updated: January 19, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
Osteoarthritis of the Knee
Device: Hyaluronic acid
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Tedec-Meiji Farma, S.A.:

Primary Outcome Measures:
  • Responders OARSI 2004 at the End of Follow-up [ Time Frame: 40 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: 7 months (6 months after first cycle) ] [ Designated as safety issue: No ]

    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 [ Time Frame: 14 months (6 months after second cycle) ] [ Designated as safety issue: No ]

    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 [ Time Frame: 21 months (6 months after third cycle) ] [ Designated as safety issue: No ]

    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 [ Time Frame: 27 months (12 months after third cycle) ] [ Designated as safety issue: No ]

    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 [ Time Frame: 34 months (6 months after fourth cycle) ] [ Designated as safety issue: No ]

    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 [ Time Frame: 40 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: 40 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: 40 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: 40 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: Throughout the study, an average of 40 months ] [ Designated as safety issue: No ]
    Consumption of rescue medication (paracetamol/NSAID) for osteoarthritis throughout the study, an average of 40 months

  • Mean Daily Dose of Paracetamol Consumption [ Time Frame: Throughout the study, an average of 40 months ] [ Designated as safety issue: No ]
    Mean daily dose of paracetamol consumption throughout the study, an average of 40 months


Enrollment: 446
Study Start Date: October 2003
Study Completion Date: December 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: hyaluronic acid
Cycles of 5 injections of hyaluronic acid at specified intervals
Device: Hyaluronic acid
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
Placebo Comparator: Placebo
Cycles of 5 injections of saline at specified intervals
Other: Placebo
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

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

Ages Eligible for Study:   45 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00669032

Sponsors and Collaborators
Tedec-Meiji Farma, S.A.
Investigators
Principal Investigator: Federico Navarro Sarabia
  More Information

Publications:
Responsible Party: Tedec-Meiji Farma, S.A.
ClinicalTrials.gov Identifier: NCT00669032     History of Changes
Other Study ID Numbers: TM-ME3710/304  2006-001854-28 
Study First Received: April 25, 2008
Results First Received: November 19, 2015
Last Updated: January 19, 2016
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Hyaluronic Acid
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Viscosupplements
Protective Agents

ClinicalTrials.gov processed this record on August 22, 2016