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| ID | Type | Description | Link |
|---|---|---|---|
| 2006-001854-28 | EudraCT Number |
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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.
To evaluate the efficacy and safety of repeated injections of hyaluronic acid compared with placebo over a period of 40 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| hyaluronic acid | Experimental | Cycles of 5 injections of hyaluronic acid at specified intervals |
|
| Placebo | Placebo Comparator | Cycles of 5 injections of saline at specified intervals |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hyaluronic acid | Device | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 40 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Federico Navarro Sarabia | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21852252 | Result | 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. |
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A total of 446 patients were screened, of whom 140 (31,4%) were screening failures. At the screening visit the patients were assessed by the blinded physician for fulfilment of the selection criteria, demographic characteristics and medical history. Knee radiographs were also obtained.
Recruiting started in October 2003 and the last follow-up was performed on July 2009. This study enrolled patients from the Rheumatology Departments belonging to 19 centres located in Spain.
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| ID | Title | Description |
|---|---|---|
| FG000 | Hyaluronic Acid (Adant) | Four cycles of 5 weekly intra-articular injections of 2.5ml 1% sodium hyaluronate with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles. |
| FG001 | Placebo | Four cycles of 5 weekly intra-articular injections of 2.5ml saline solution with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Considering a statistical power of 80% and assuming up to a 40% dropout rate, the sample size was planned to include a total of 300 patients (150 per treatment arm). Analysis was performed based on the modified intention-to-treat population. The imputation method for handling missing data was the last observation carried forward.
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| ID | Title | Description |
|---|---|---|
| BG000 | Hyaluronic Acid (Adant) | Four cycles of 5 weekly intra-articular injections of 2.5ml 1% sodium hyaluronate with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of responders | 40 months |
|
40 months
Treatment safety and tolerability was evaluated based on the incidence and type of adverse events and the results of blood laboratory tests and physical examinations throughout the duration of the study. Safety analyses were performed in those patients who received at least one intra-articular injection (safety population).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Hyaluronic Acid (Adant) | Four cycles of 5 weekly intra-articular injections of 2.5ml 1% sodium hyaluronate with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic reaction | Immune system disorders | MedDRA (Unspecified) | Systematic Assessment |
Control of rescue medication: patients were asked at every assessment visit about the frequency and doses of consumption, but it was not delivered in hand.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| R&D Director | Tedec-Meiji Farma, S.A. | 918870980 | m.gimeno@tedecmeiji.com |
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| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
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| Placebo | Other | 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 |
|
| 7 months (6 months after first cycle) |
| 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. | 14 months (6 months after second cycle) |
| 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. | 21 months (6 months after third cycle) |
| 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. | 27 months (12 months after third cycle) |
| 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. | 34 months (6 months after fourth cycle) |
| 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. | 40 months |
| 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. | 40 months |
| 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. | 40 months |
| 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. | 40 months |
| 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 | 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 | Throughout the study, an average of 40 months |
| Withdrawal by Subject |
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| Adverse Event |
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| Physician Decision |
|
| No fulfilment of the selection criteria |
|
Four cycles of 5 weekly intra-articular injections of 2.5ml saline solution with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles.
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| Duration knee osteoarthritis | Mean | Standard Deviation | years |
|
| OG000 |
| Hyaluronic Acid (Adant) |
Four cycles of 5 weekly intra-articular injections of 2.5ml 1% sodium hyaluronate with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles. |
| OG001 | Placebo | Four cycles of 5 weekly intra-articular injections of 2.5ml saline solution with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles. |
|
|
|
| Secondary | 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. | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of responders | 7 months (6 months after first cycle) |
|
|
|
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| Secondary | 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. | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of responders | 14 months (6 months after second cycle) |
|
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| Secondary | 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. | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of responders | 21 months (6 months after third cycle) |
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| Secondary | 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. | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of responders | 27 months (12 months after third cycle) |
|
|
|
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| Secondary | 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. | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of responders | 34 months (6 months after fourth cycle) |
|
|
|
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| Secondary | 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. | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of patients | 40 months |
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|
|
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| Secondary | 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. | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of patients | 40 months |
|
|
|
|
| Secondary | 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. | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of patients | 40 months |
|
|
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| Secondary | 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. | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of patients | 40 months |
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| Secondary | 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 | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Number | percentage of patients | Throughout the study, an average of 40 months |
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| Secondary | Mean Daily Dose of Paracetamol Consumption | Mean daily dose of paracetamol consumption throughout the study, an average of 40 months | The modified intention-to-treat population included all randomly assigned patients with at least one efficacy assessment after randomisation. | Posted | Mean | Standard Deviation | mg/day | Throughout the study, an average of 40 months |
|
|
|
| 0 |
| 153 |
| 11 |
| 153 |
| EG001 | Placebo | Four cycles of 5 weekly intra-articular injections of 2.5ml saline solution with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles. | 0 | 153 | 11 | 153 |
| Pain at injection site | General disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Bleeding at injection site | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Heaviness feeling | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Bleeding | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
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The only disclosure restriction on the PIs is that the study results will be presented during scientific meetings or published in scientific journals with prior agreement with the sponsor.
| D012216 |
| Rheumatic Diseases |