Knee Osteoarthritis
Conditions
Brief summary
The clinical efficacy of hyaluronic acid or corticosteroid injections has been reported, but effects are short lived. This has led to the development of additional injection options such as autologous derived blood products which have been documented to alleviate symptoms related to knee osteoarthritis, with recent comparative studies suggesting a greater, long-lasting effect with these blood derived products like platelet rich plasma (PRP) \[2-8\]. One clinically-developed preparation of platelet rich plasma, named autologous conditioned plasma (ACP), has randomized controlled trial data proving efficacy \[4,9\]. Clinical use of platelet rich plasma for knee arthritis typically involves a 3-injection series over 3 weeks, i.e. an injection once a week for three weeks. The main objective of this study is to determine if hyaluronic acid (HA) injected at the same time as autologous conditioned plasma (ACP), a leukocyte-poor platelet rich plasma product, will improve the performance of ACP in the treatment of symptomatic knee osteoarthritis. It is hypothesized that the injection of hyaluronic acid will improve the efficacy of ACP.
Detailed description
Patients between the ages of 30 and 80 who have documented radiographic evidence of OA in the tibiofemoral or patellofemoral compartment of the target knee (Kellgren-Lawrence grades 1-4) will be screened for participation in this study. Patients must have a documented diagnosis of primary OA for at least six weeks. 80 patients will be recruited through the Andrews Institute physician practices. The study design will be a randomized control trial. Participants who meet the inclusion criteria will have the study explained in detail, and informed consent will be obtained as outlined above. Participants will complete patient-reported outcome questionnaires prior to their injection. The questionnaires will include the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS). Participants will also complete these questionnaires at 1, 3, 6, 12, 18, and 24 months after the final injection. A trained medical professional will draw blood from the patient's arm, and the blood will be spun in a centrifuge for 5 minutes at 1500 RPM. The platelets will then be separated for injection into the patient's knee. The treating physician will then inject the ACP into the involved knee joint following standard aseptic technique per the physician's standard of care. This entire process will be completed in a single patient visit. Any unused portion of a sample in the physician's office will be disposed of through standard biohazard waste disposal systems as required by law. Group 1 \[ACP\]: Will receive three intra-articular injections of autologous conditioned plasma dosed once a week for three weeks. Group 2 \[ACP-HA\]: Will receive two intra-articular injections of autologous conditioned plasma and hyaluronic acid once a week for two weeks and a third injection on the third week of ACP.
Interventions
DRUGHyaluronan
Patients will receive 2 intra-articular injections of autologous conditioned plasma and hyaluronic acid once a week for 2 weeks and a third injection on the third week of ACP.
BIOLOGICALAutologous conditioned plasma
Patients will receive 3 intra-articular injections of autologous conditioned plasma dosed at once a week for 3 weeks.
Sponsors
Andrews Research & Education Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participants will be blinded to the type of injection that they receive.
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients between the ages of 30 and 80 * Documented radiographic evidence of OA in the tibiofemoral or patellofemoral compartment of the involved knee (Kellgren-Lawrence grades 1-4) * Patients must have a documented diagnosis of primary OA for at least 6 weeks.
Exclusion criteria
* Patients who have had viscosupplementation in the involved knee in the past 6 months. * Any patient who has had a corticosteroid injection in any joint within 3-months prior to screening will be excluded. * Patients with gout or rheumatologic disease will be excluded. Patients who have had a previous negative experience with HA. * Any patient who will have difficulty obtaining internet access, does not have an active e-mail address, or is unable to comprehend study documents or give informed consent will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post injections | Patient reported outcome measure; The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total score. Higher scores indicate worse pain, stiffness, and functional limitations. |
| International Knee Documentation Committee Subjective Knee Evaluation Form | Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post injections | Patient reported outcome measure; Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function. |
| Knee Injury and Osteoarthritis Outcome Score | Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post injections | Patient reported outcome measure; A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Autologous Conditioned Plasma Group Participants in this group will receive a three-injection series of autologous conditioned plasma over the course of 3 consecutive weeks.
Autologous conditioned plasma: Patients will receive 3 intra-articular injections of autologous conditioned plasma dosed at once a week for 3 weeks. | 32 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group Participants in this group will receive a two-injection series of autologous conditioned plasma and hyaluronic acid (Hymovis, Fidia Pharmaceuticals) and a third injection on the third week of autologous conditioned plasma.
Hyaluronan: Patients will receive 2 intra-articular injections of autologous conditioned plasma and hyaluronic acid once a week for 2 weeks and a third injection on the third week of ACP. | 32 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 11 | 10 |
Baseline characteristics
| Characteristic | Autologous Conditioned Plasma Group | Total | Autologous Conditioned Plasma With Hyaluronic Acid Group |
|---|---|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 11.4 | 58.25 years STANDARD_DEVIATION 9.79 | 60.7 years STANDARD_DEVIATION 9 |
| IKDC | 39.2 Score STANDARD_DEVIATION 10.4 | 38.9 Score STANDARD_DEVIATION 12.52 | 38.6 Score STANDARD_DEVIATION 14.5 |
| KOOS | 42.7 Score STANDARD_DEVIATION 12.7 | 43.5 Score STANDARD_DEVIATION 13.49 | 44.3 Score STANDARD_DEVIATION 14.4 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 19 Participants | 35 Participants | 16 Participants |
| Sex: Female, Male Male | 13 Participants | 29 Participants | 16 Participants |
| WOMAC | 40 Score STANDARD_DEVIATION 18.6 | 40.25 Score STANDARD_DEVIATION 18.5 | 40.5 Score STANDARD_DEVIATION 18.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 0 / 32 | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 |
Outcome results
Primary
International Knee Documentation Committee Subjective Knee Evaluation Form
Patient reported outcome measure; Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function.
Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post injections
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous Conditioned Plasma Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 1 Month | 50.1 score on a scale | Standard Deviation 17.3 |
| Autologous Conditioned Plasma Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 3 Months | 50.4 score on a scale | Standard Deviation 17.6 |
| Autologous Conditioned Plasma Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 6 Months | 53.1 score on a scale | Standard Deviation 16 |
| Autologous Conditioned Plasma Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 12 Months | 50.6 score on a scale | Standard Deviation 19.1 |
| Autologous Conditioned Plasma Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 18 Months | 57 score on a scale | Standard Deviation 23.6 |
| Autologous Conditioned Plasma Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 24 Months | 50.9 score on a scale | Standard Deviation 20.1 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 18 Months | 53.4 score on a scale | Standard Deviation 24.5 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 1 Month | 53.7 score on a scale | Standard Deviation 14.1 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 12 Months | 55.7 score on a scale | Standard Deviation 21.5 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 3 Months | 56.9 score on a scale | Standard Deviation 17.6 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 24 Months | 51.8 score on a scale | Standard Deviation 21.9 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | International Knee Documentation Committee Subjective Knee Evaluation Form | 6 Months | 53.1 score on a scale | Standard Deviation 19.9 |
Primary
Knee Injury and Osteoarthritis Outcome Score
Patient reported outcome measure; A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated.
Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post injections
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous Conditioned Plasma Group | Knee Injury and Osteoarthritis Outcome Score | 6 months | 64.2 score | Standard Deviation 16.3 |
| Autologous Conditioned Plasma Group | Knee Injury and Osteoarthritis Outcome Score | 1 Month | 59.4 score | Standard Deviation 13.5 |
| Autologous Conditioned Plasma Group | Knee Injury and Osteoarthritis Outcome Score | 3 Months | 59 score | Standard Deviation 18.8 |
| Autologous Conditioned Plasma Group | Knee Injury and Osteoarthritis Outcome Score | 12 Months | 61.8 score | Standard Deviation 17.7 |
| Autologous Conditioned Plasma Group | Knee Injury and Osteoarthritis Outcome Score | 18 Months | 65.3 score | Standard Deviation 18.2 |
| Autologous Conditioned Plasma Group | Knee Injury and Osteoarthritis Outcome Score | 24 Months | 59.8 score | Standard Deviation 19.5 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Knee Injury and Osteoarthritis Outcome Score | 18 Months | 59.8 score | Standard Deviation 19.5 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Knee Injury and Osteoarthritis Outcome Score | 6 months | 62.5 score | Standard Deviation 18.1 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Knee Injury and Osteoarthritis Outcome Score | 12 Months | 61.8 score | Standard Deviation 20.4 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Knee Injury and Osteoarthritis Outcome Score | 1 Month | 62.7 score | Standard Deviation 12.5 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Knee Injury and Osteoarthritis Outcome Score | 24 Months | 59 score | Standard Deviation 24.4 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Knee Injury and Osteoarthritis Outcome Score | 3 Months | 62.9 score | Standard Deviation 20.5 |
Primary
Western Ontario and McMaster University's Osteoarthritis Index (WOMAC)
Patient reported outcome measure; The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total score. Higher scores indicate worse pain, stiffness, and functional limitations.
Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post injections
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous Conditioned Plasma Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 1 Month | 24.9 score on a scale | Standard Deviation 15.6 |
| Autologous Conditioned Plasma Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 3 Months | 26.1 score on a scale | Standard Deviation 20.1 |
| Autologous Conditioned Plasma Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 6 Months | 21.9 score on a scale | Standard Deviation 15.3 |
| Autologous Conditioned Plasma Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 12 Months | 25.9 score on a scale | Standard Deviation 18.7 |
| Autologous Conditioned Plasma Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 18 Months | 21 score on a scale | Standard Deviation 15.1 |
| Autologous Conditioned Plasma Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 24 Months | 26.7 score on a scale | Standard Deviation 17.8 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 18 Months | 27.1 score on a scale | Standard Deviation 23.8 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 1 Month | 22.4 score on a scale | Standard Deviation 15.2 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 12 Months | 22.7 score on a scale | Standard Deviation 19.3 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 3 Months | 22.3 score on a scale | Standard Deviation 16.3 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 24 Months | 29.2 score on a scale | Standard Deviation 23.3 |
| Autologous Conditioned Plasma With Hyaluronic Acid Group | Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) | 6 Months | 22.5 score on a scale | Standard Deviation 16.5 |