Knee OsteoarthritisPhase 4NCT03825133
The Comparison of Knee Osteoarthritis Treatment With Bone Marrow Aspirate Concentrate , Leukocyte Rich Platelet Rich Plasma and Hyaluronic Acid
A Phase 4 study testing Bone Marrow Aspirate Concentrate, Leukocyte Rich Platelet Rich Plasma and Hyaluronic Acid in people with Knee Osteoarthritis, run by Clinical Center of Vojvodina at 1 site in Serbia.
Trial summary
The aim of this study is to compare therapeutic and clinical effects of intra-articular injection of Bone Marrow Aspirate Concentrate (BMAC), inta-articular injection of Leukocyte Rich Platelet Rich plasma (LR-PRP) and 3 weekly doses of high molecular weight of Hyaluronic acid for the treatment of osteoarthritis (OA)… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- Bone Marrow Aspirate Concentrate, Leukocyte Rich Platelet Rich Plasma and Hyaluronic Acid
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteSerbia
- Study dates
- 1 Apr 2016to 30 Nov 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- history of complaints of knee pain because of the Knee Osteoarthritis with no relief using anti-inflammatory agents even after 3 months,
- Kellgren-Lawrence (KL) grade 2-4
- normal blood results and coagulation profile (platelets 150,000-450,000/l),
- patients who had not undergone any surgery on the affected knee within 2 years prior to the first injection and
- Mentally fit for clinical study
Who cannot join
- severe knee instability,
- severe misalignment,
- unicompartmental OA
- BMI more than 35
- inflammatory arthritis such as rheumatoid arthritis and ankylosing spondylitis
- presenting muscle pain underlying diseases such as hematologic disorders, septicemia, coagulopathy, neoplasm, active infection, and immune deficiency
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Comparison of Knee Osteoarthritis Treatment With Single-dose of Bone Marrow Aspirate Concentrate, Single-dose of Leukocyte Rich Platelet Rich Plasma and 3 Injection of High Molecular Weight Hyaluronic Acid-A Randomized Clinical Trial
The aim of this study is to compare therapeutic and clinical effects of intra-articular injection of Bone Marrow Aspirate Concentrate (BMAC), inta-articular injection of Leukocyte Rich Platelet Rich plasma (LR-PRP) and 3 weekly doses of high molecular weight of Hyaluronic acid for the treatment of osteoarthritis (OA) of the knee ( KL scale II-IV).
Read the detailed description
Osteoarthritis (OA) is the most common joint disease worldwide, affecting an estimated 10% of men and 18% of women over 60 years of age with the knee and hip joints predominantly involved. The pain and loss of function can be debilitating; in developed countries the resultant socioeconomic burden is large costing between 1, 0% and 2, 5% of gross domestic product. Several therapeutic options for the treatment of OA are widely used, consists of pain management, physical therapy with life-modifying recommendations, joint injections with joint replacement for end-stage disease. Intra-articular drug delivery has several advantages over systemic delivery, including increased local bioavailability, reduced systemic exposure, fewer adverse events and reduced cost. Three injectable materials have been widely used for intra-articular treatment of the knee OA: corticosteroids (with or without local anesthetics), hyaluronic acid based preparations and in the last decade biologic preparations, such as human serum albumin, TNF and Il-1 inhibitors, platelet-rich plasma (PRP) injections, bone marrow-derived stem cells (BMSCs), adipose-derived stem cells (ADSCs) and amnion-derived mesenchymal stem cells (AMSCs) etc PRP is promising therapeutic option for the OA treatment, there are still many concerns with PRP's efficiency. Among all questions, ( Number of platelets, percentage in accordance with baseline, frequency of doses etc.) presence or absence of different cells in PRP formulations ( as leukocytes), could significantly change an overall clinical result. In general, PRP could be Leukocyte-rich (LR- with increase number of Leukocytes in comparison with baseline number) and Leukocyte-poor.
Another option that has become more popular for physicians treating this debilitation condition is BMAC, which use undifferentiated cells found in the bone marrow to promote healing and tissue regeneration. These cells have the ability to replicate into a multiple different tissue types. With BMAC, the marrow is concentrated provide better healing of the damaged tissue and aid in growth and repair. The full benefits of BMAC are still unknown, but studies have shown the treatment can reduce swelling, relieve pain, and improve healing in articular cartilage and bone grafts.
Autologous BMAC has shown promising clinical potential as a therapeutic agent in regenerative medicine, including the treatment of osteoarthritis and cartilage defects, and the clinical efficacy platelet rich plasma has been documented to alleviate symptoms related to knee osteoarthritis. However, randomized, prospective comparison of the two techniques has not been reported in the literature and long term follow-up for both treatments is limited, and especially limited in the use of BMAC for the knee OA treatment.
From the other hand, HA preparations are widely used in everyday practice for almost 30 years with variable results. No one of these therapeutic options are not yet recommended by supreme professional organizations ( e.g.AAOS) because of paulacity of scientific data and unbiased confirmation of their clinical efficiency with a broad advice for necessity of more rigorous clinical trials.
- Conditions
- Knee Osteoarthritis
- Being tested
- Bone Marrow Aspirate Concentrate, Leukocyte Rich Platelet Rich Plasma, Hyaluronic Acid
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bone Marrow Aspirate ConcentrateProcedure or surgery
Also called BMAC
Bone marrow ( 100 ml) is aspirated from proximal tibia, concentrated in Arthrex Angel Centrifuge, and after concentration 6 ml of BMAC is injected in the knee
Leukocyte Rich Platelet Rich PlasmaProcedure or surgery
Also called LR-PRP
Blood sample is taken ( 100 ml), centrifuged in Arthrex Angel Centrifuge and after double spinning process about 6 ml of PRP is injected in the knee
Hyaluronic AcidDrug
Also called HA
Three injections of Cartinorm (1% Sodium Hyaluronat (20mg/2 ml) by Goodwill Pharma) is injected in the knee weekly
| Study group | Role | What they receive |
|---|---|---|
| Bone Marrow Aspirate Concentrate | Experimental | Patients treated with single injection of BMAC in the knee Receives: Procedure: Bone Marrow Aspirate Concentrate |
| Leukocyte Rich Platelet Rich Plasma | Experimental | Patients treated with single injection of LR-PRP in the knee Receives: Procedure: Leukocyte Rich Platelet Rich Plasma |
| Hyaluronic Acid | Experimental | Patients treated with 3 single injection of high molecular HA in the knee ( one injection weekly) Receives: Drug: Hyaluronic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
change of WOMAC
Purpose of WOMAC scale is to assess the course of disease or response to treatment in patients with knee or hip osteoarthritis (OA).Content: Three subscales, 24 items.: 1) pain severity during various positions or movements, 2) severity of joint stiffness, and 3) difficulty performing daily functional activities.Response options/scale: In the Likert version, each item offers 5 responses: "none" scored as 0, "mild" as 1,"moderate" as 2, "severe" as 3, and "extreme" as 4. Alternatively, the VAS and numerical rating scale versions permit responses to be selected on a 100-mm or 11-box horizontal scale, respectively, with the left end marked as "none" and the right end marked as "extreme". The range for possible subscale scores in the Likert format are: pain (0-20; 5 items each scored 0-4), stiffness (2 items, 0-8), and physical function (17 items, 0-68). Score interpretation: Higher scores indicate worse pain, stiffness, or physical function.
Measured: after 1, 3, 6, 9 and 12 months
Change of KOOS
Purpose of KOOS is To measure patients' opinions about their knee and associated problems over short- and long-term follow- up Intended populations/conditions: young and middle-aged people with posttraumatic osteoarthritis (OA), as well as those with injuries that may lead to post traumatic OA (e.g., ACL, meniscal, osteochondral injury) Content. Five domains: 1) pain frequency and severity during functional activities; 2) symptoms such as the severity of knee stiffness and the presence of swelling, grinding or clicking, catching, and range of motion restriction; 3) difficulty experienced during activities of daily living; 4) difficulty experienced with sport and recreational activities; and 5) knee-related quality of life.Number of items: 42 items across 5 subscales.
Score interpretation: 0- extreme problems and 100- no problems.
Measured: after 1, 3, 6, 9 and 12 months
Secondary outcomes (5)
change of SF-36
The SF-36 is multi-item generic health surveys intended to measure "general health concepts not specific to any age, disease, or treatment group" . The original objective was to develop a short, generic health-status measure that reproduces the 2 summary scores of the SF-36, i.e., the physical component summary (PCS) score and the mental component summary (MCS) score (2).
The SF-36 consists of 36 items, 35 of which are used in the calculation of 8 separate scale scores. The physical functioning scale (10 items) is the longest scale.
Scores on the SF-36 and SF-12 scales range from 0-100, with higher scores indicating better health. On the physical functioning scale, low scores are typical of someone who experiences many limitations in physical activities, including bathing or dressing, while high scores represent someone who is able to perform these types of activities without limitations
Measured: after 1, 3, 6, 9 and 12 months
Change of IKDC
Purpose of IKDC is to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment Intended populations/conditions: Patients with a variety of knee conditions, including ligament injuries, meniscal injuries, articular cartilage lesions, and patellofemoral pain.
Content: Three domains: 1) symptoms, including pain, stiffness, swelling, locking/catching, and giving way; 2) sports and daily activities; and 3) current knee function and knee function prior to knee injury (not included in the total score).
Number of items.18 (7 items for symptoms, 1 item for sport participation, 9 items for daily activities, and 1 item for current knee function).
Possible score range 0-100, where 100 means no limitation with daily or sporting activities and the absence of symptoms.
Measured: after 1, 3, 6, 9 and 12 months
change of VAS pain
The pain VAS is a unidimensional measure of pain intensity, which has been widely used in diverse adult populations, including those with rheumatic diseases .The pain VAS is a continuous scale comprised of a horizontal (HVAS) or vertical (VVAS) line, usually 10 centimeters (100 mm) in length, anchored by 2 verbal descriptors, one for each symptom extreme. Instructions, time period for reporting, and verbal descriptor anchors have varied widely in the literature depending on intended use of the scale.The pain VAS is a single-item scale. For pain intensity, the scale is most commonly anchored by "no pain" (score of 0) and "pain as bad as it could be" or "worst imaginable pain" (score of 100 [100-mm scale]) (6-8). To avoid clustering of scores around a preferred numeric value, numbers or verbal descriptors at intermediate points are not recommended .A higher score indicates greater pain intensity.
Measured: after 3, 7 14 and 21 days
VAS pain injection
The pain VAS is a unidimensional measure of pain intensity, which has been widely used in diverse adult populations, including those with rheumatic diseases .The pain VAS is a continuous scale comprised of a horizontal (HVAS) or vertical (VVAS) line, usually 10 centimeters (100 mm) in length, anchored by 2 verbal descriptors, one for each symptom extreme. Instructions, time period for reporting, and verbal descriptor anchors have varied widely in the literature depending on intended use of the scale.The pain VAS is a single-item scale. For pain intensity, the scale is most commonly anchored by "no pain" (score of 0) and "pain as bad as it could be" or "worst imaginable pain" (score of 100 [100-mm scale]) (6-8). To avoid clustering of scores around a preferred numeric value, numbers or verbal descriptors at intermediate points are not recommended .A higher score indicates greater pain intensity.
Measured: up to 10 minutes after after intervention
VAS score after injection of fluid
The pain VAS is a unidimensional measure of pain intensity, which has been widely used in diverse adult populations, including those with rheumatic diseases .The pain VAS is a continuous scale comprised of a horizontal (HVAS) or vertical (VVAS) line, usually 10 centimeters (100 mm) in length, anchored by 2 verbal descriptors, one for each symptom extreme. Instructions, time period for reporting, and verbal descriptor anchors have varied widely in the literature depending on intended use of the scale.The pain VAS is a single-item scale. For pain intensity, the scale is most commonly anchored by "no pain" (score of 0) and "pain as bad as it could be" or "worst imaginable pain" (score of 100 [100-mm scale]) (6-8). To avoid clustering of scores around a preferred numeric value, numbers or verbal descriptors at intermediate points are not recommended .A higher score indicates greater pain intensity.
Measured: up to 10 minutes after after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2019
- Study start1 Apr 2016
- Primary completion30 Nov 2017
- Study completion30 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomly assigned to 3 groups: LR-PRP group, the BMAC group or HA group. Functional scores and outcomes will be compared to determine clinical efficacy of all groups and which treatment is more effective in treating knee OA
- Masking
- None (open label)
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinical Center of Vojvodina
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, dr Oliver Dulic, Clinical Center of Vojvodina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03825133
- Sponsor's protocol ID
- CCVBMACKnee
- Status last verified
- Feb 2019
- First submitted
- 23 Jan 2019
- Last updated
- 7 Feb 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: de-identified individual participant data for all primary and secondary outcome measures will be made available.
Publications
Chahla J, Alland JA, Verma NN. Bone Marrow Aspirate Concentrate for Orthopaedic Use. Orthop Nurs. 2018 Nov/Dec;37(6):379-381. doi: 10.1097/NOR.0000000000000502.
PubMed 30451775Chahla J, Mandelbaum BR. Biological Treatment for Osteoarthritis of the Knee: Moving from Bench to Bedside-Current Practical Concepts. Arthroscopy. 2018 May;34(5):1719-1729. doi: 10.1016/j.arthro.2018.01.048. Epub 2018 Apr 5.
PubMed 29628381Jones IA, Togashi R, Wilson ML, Heckmann N, Vangsness CT Jr. Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol. 2019 Feb;15(2):77-90. doi: 10.1038/s41584-018-0123-4.
PubMed 30498258Chahla J, Dean CS, Moatshe G, Pascual-Garrido C, Serra Cruz R, LaPrade RF. Concentrated Bone Marrow Aspirate for the Treatment of Chondral Injuries and Osteoarthritis of the Knee: A Systematic Review of Outcomes. Orthop J Sports Med. 2016 Jan 13;4(1):2325967115625481. doi: 10.1177/2325967115625481. eCollection 2016 Jan.
PubMed 26798765Chu CR, Rodeo S, Bhutani N, Goodrich LR, Huard J, Irrgang J, LaPrade RF, Lattermann C, Lu Y, Mandelbaum B, Mao J, McIntyre L, Mishra A, Muschler GF, Piuzzi NS, Potter H, Spindler K, Tokish JM, Tuan R, Zaslav K, Maloney W. Optimizing Clinical Use of Biologics in Orthopaedic Surgery: Consensus Recommendations From the 2018 AAOS/NIH U-13 Conference. J Am Acad Orthop Surg. 2019 Jan 15;27(2):e50-e63. doi: 10.5435/JAAOS-D-18-00305.
PubMed 30300216Filardo G, Di Matteo B, Kon E, Dhillon MS, Patel S, Marwaha N. Platelet-rich plasma for knee osteoarthritis. Am J Sports Med. 2013 Sep;41(9):NP42-3. doi: 10.1177/0363546513502635. No abstract available.
PubMed 23997229Evans CH, Kraus VB, Setton LA. Progress in intra-articular therapy. Nat Rev Rheumatol. 2014 Jan;10(1):11-22. doi: 10.1038/nrrheum.2013.159. Epub 2013 Nov 5.
PubMed 24189839Garratt AM, Brealey S, Gillespie WJ; DAMASK Trial Team. Patient-assessed health instruments for the knee: a structured review. Rheumatology (Oxford). 2004 Nov;43(11):1414-23. doi: 10.1093/rheumatology/keh362. Epub 2004 Aug 17.
PubMed 15316121Dulic O, Abazovic D, Matijevic S, Rasovic P, Obradovic M, Bjelobrk M, Tosic M, Lalic I, Baljak B, Milinkov M. Quality of life changes in patients suffering from knee osteoarthritis treated with bone marrow aspirate concentrate, platelet-rich plasma and hyaluronic acid injections. Regen Med. 2025 Feb-Mar;20(2-3):87-96. doi: 10.1080/17460751.2025.2472589. Epub 2025 Mar 3.
PubMed 40028743Rasovic P, Dulic O, Lalic I, Matijevic R, Janjic N, Tosic M, Aleksandric D, Abazovic D, Miskulin M, Matijevic S, Kovacevic L. The role of osteoarthritis severity, BMI and age on clinical efficacy of bone marrow aspirate concentrate in the treatment of knee osteoarthritis. Regen Med. 2023 Sep;18(9):735-747. doi: 10.2217/rme-2023-0042. Epub 2023 Aug 14.
PubMed 37577967Dulic O, Lalic I, Kecojevic V, Gavrilovic G, Abazovic D, Miskulin M, Maric D, Bumbasirevic M. Do knee injection portals affect clinical results of bone marrow aspirate concentrate injection in the treatment of osteoarthritis? A prospective randomized controlled study. Regen Med. 2020 Aug;15(8):1987-2000. doi: 10.2217/rme-2020-0020. Epub 2020 Nov 5.
PubMed 33151802
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Comparison of Knee Osteoarthritis Treatment With Single-dose of Bone Marrow Aspirate Concentrate, Single-dose of Leukocyte Rich Platelet Rich Plasma and 3 Injection of High Molecular Weight Hyaluronic Acid-A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03825133
- Acronym / sponsor ID
- CCVBMACKnee
- Conditions
- Knee Osteoarthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Clinical Center of VojvodinaUniversity, hospital or other
- Study start
- 1 Apr 2016 (actual)
- Primary completion
- 30 Nov 2017 (actual)
- Study completion
- 30 Nov 2017 (actual)
- First posted
- 31 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to compare therapeutic and clinical effects of intra-articular injection of Bone Marrow Aspirate Concentrate (BMAC), inta-articular injection of Leukocyte Rich Platelet Rich plasma (LR-PRP) and 3 weekly doses of high molecular weight of Hyaluronic acid for the treatment of osteoarthritis (OA) of the knee ( KL scale II-IV).
Detailed description
Osteoarthritis (OA) is the most common joint disease worldwide, affecting an estimated 10% of men and 18% of women over 60 years of age with the knee and hip joints predominantly involved. The pain and loss of function can be debilitating; in developed countries the resultant socioeconomic burden is large costing between 1, 0% and 2, 5% of gross domestic product. Several therapeutic options for the treatment of OA are widely used, consists of pain management, physical therapy with life-modifying recommendations, joint injections with joint replacement for end-stage disease. Intra-articular drug delivery has several advantages over systemic delivery, including increased local bioavailability, reduced systemic exposure, fewer adverse events and reduced cost. Three injectable materials have been widely used for intra-articular treatment of the knee OA: corticosteroids (with or without local anesthetics), hyaluronic acid based preparations and in the last decade biologic preparations, such as human serum albumin, TNF and Il-1 inhibitors, platelet-rich plasma (PRP) injections, bone marrow-derived stem cells (BMSCs), adipose-derived stem cells (ADSCs) and amnion-derived mesenchymal stem cells (AMSCs) etc PRP is promising therapeutic option for the OA treatment, there are still many concerns with PRP's efficiency. Among all questions, ( Number of platelets, percentage in accordance with baseline, frequency of doses etc.) presence or absence of different cells in PRP formulations ( as leukocytes), could significantly change an overall clinical result. In general, PRP could be Leukocyte-rich (LR- with increase number of Leukocytes in comparison with baseline number) and Leukocyte-poor.
Another option that has become more popular for physicians treating this debilitation condition is BMAC, which use undifferentiated cells found in the bone marrow to promote healing and tissue regeneration. These cells have the ability to replicate into a multiple different tissue types. With BMAC, the marrow is concentrated provide better healing of the damaged tissue and aid in growth and repair. The full benefits of BMAC are still unknown, but studies have shown the treatment can reduce swelling, relieve pain, and improve healing in articular cartilage and bone grafts.
Autologous BMAC has shown promising clinical potential as a therapeutic agent in regenerative medicine, including the treatment of osteoarthritis and cartilage defects, and the clinical efficacy platelet rich plasma has been documented to alleviate symptoms related to knee osteoarthritis. However, randomized, prospective comparison of the two techniques has not been reported in the literature and long term follow-up for both treatments is limited, and especially limited in the use of BMAC for the knee OA treatment.
From the other hand, HA preparations are widely used in everyday practice for almost 30 years with variable results. No one of these therapeutic options are not yet recommended by supreme professional organizations ( e.g.AAOS) because of paulacity of scientific data and unbiased confirmation of their clinical efficiency with a broad advice for necessity of more rigorous clinical trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Patients will be randomly assigned to 3 groups: LR-PRP group, the BMAC group or HA group. Functional scores and outcomes will be compared to determine clinical efficacy of all groups and which treatment is more effective in treating knee OA
| Arm | Type | Receives |
|---|---|---|
| Bone Marrow Aspirate Concentrate | Experimental | Procedure: Bone Marrow Aspirate ConcentratePatients treated with single injection of BMAC in the knee |
| Leukocyte Rich Platelet Rich Plasma | Experimental | Procedure: Leukocyte Rich Platelet Rich PlasmaPatients treated with single injection of LR-PRP in the knee |
| Hyaluronic Acid | Experimental | Drug: Hyaluronic AcidPatients treated with 3 single injection of high molecular HA in the knee ( one injection weekly) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- history of complaints of knee pain because of the Knee Osteoarthritis with no relief using anti-inflammatory agents even after 3 months,
- Kellgren-Lawrence (KL) grade 2-4
- normal blood results and coagulation profile (platelets 150,000-450,000/l),
- patients who had not undergone any surgery on the affected knee within 2 years prior to the first injection and
- Mentally fit for clinical study
Key exclusion criteria (6 listed)
- severe knee instability,
- severe misalignment,
- unicompartmental OA
- BMI more than 35
- inflammatory arthritis such as rheumatoid arthritis and ankylosing spondylitis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bone Marrow Aspirate ConcentrateAlso: BMACBone marrow ( 100 ml) is aspirated from proximal tibia, concentrated in Arthrex Angel Centrifuge, and after concentration 6 ml of BMAC is injected in the knee | Procedure or surgery | Bone Marrow Aspirate Concentrate |
| Leukocyte Rich Platelet Rich PlasmaAlso: LR-PRPBlood sample is taken ( 100 ml), centrifuged in Arthrex Angel Centrifuge and after double spinning process about 6 ml of PRP is injected in the knee | Procedure or surgery | Leukocyte Rich Platelet Rich Plasma |
| Hyaluronic AcidAlso: HAThree injections of Cartinorm (1% Sodium Hyaluronat (20mg/2 ml) by Goodwill Pharma) is injected in the knee weekly | Drug | Hyaluronic Acid |
Primary outcome
change of WOMAC
Time frame: after 1, 3, 6, 9 and 12 months
Purpose of WOMAC scale is to assess the course of disease or response to treatment in patients with knee or hip osteoarthritis (OA).Content: Three subscales, 24 items.: 1) pain severity during various positions or movements, 2) severity of joint stiffness, and 3) difficulty performing daily functional activities.Response options/scale: In the Likert version, each item offers 5 responses: "none" scored as 0, "mild" as 1,"moderate" as 2, "severe" as 3, and "extreme" as 4. Alternatively, the VAS and numerical rating scale versions permit responses to be selected on a 100-mm or 11-box horizontal scale, respectively, with the left end marked as "none" and the right end marked as "extreme". The range for possible subscale scores in the Likert format are: pain (0-20; 5 items each scored 0-4), stiffness (2 items, 0-8), and physical function (17 items, 0-68). Score interpretation: Higher scores indicate worse pain, stiffness, or physical function.
Change of KOOS
Time frame: after 1, 3, 6, 9 and 12 months
Purpose of KOOS is To measure patients' opinions about their knee and associated problems over short- and long-term follow- up Intended populations/conditions: young and middle-aged people with posttraumatic osteoarthritis (OA), as well as those with injuries that may lead to post traumatic OA (e.g., ACL, meniscal, osteochondral injury) Content. Five domains: 1) pain frequency and severity during functional activities; 2) symptoms such as the severity of knee stiffness and the presence of swelling, grinding or clicking, catching, and range of motion restriction; 3) difficulty experienced during activities of daily living; 4) difficulty experienced with sport and recreational activities; and 5) knee-related quality of life.Number of items: 42 items across 5 subscales. Score interpretation: 0- extreme problems and 100- no problems.
5 secondary outcomes
change of SF-36
Time frame: after 1, 3, 6, 9 and 12 months
Change of IKDC
Time frame: after 1, 3, 6, 9 and 12 months
change of VAS pain
Time frame: after 3, 7 14 and 21 days
VAS pain injection
Time frame: up to 10 minutes after after intervention
VAS score after injection of fluid
Time frame: up to 10 minutes after after intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2019.
- Background: PubMed 30451775Chahla J, Alland JA, Verma NN. Bone Marrow Aspirate Concentrate for Orthopaedic Use. Orthop Nurs. 2018 Nov/Dec;37(6):379-381. doi: 10.1097/NOR.0000000000000502.
- Background: PubMed 29628381Chahla J, Mandelbaum BR. Biological Treatment for Osteoarthritis of the Knee: Moving from Bench to Bedside-Current Practical Concepts. Arthroscopy. 2018 May;34(5):1719-1729. doi: 10.1016/j.arthro.2018.01.048. Epub 2018 Apr 5.
- Background: PubMed 30498258Jones IA, Togashi R, Wilson ML, Heckmann N, Vangsness CT Jr. Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol. 2019 Feb;15(2):77-90. doi: 10.1038/s41584-018-0123-4.
- Background: PubMed 26798765Chahla J, Dean CS, Moatshe G, Pascual-Garrido C, Serra Cruz R, LaPrade RF. Concentrated Bone Marrow Aspirate for the Treatment of Chondral Injuries and Osteoarthritis of the Knee: A Systematic Review of Outcomes. Orthop J Sports Med. 2016 Jan 13;4(1):2325967115625481. doi: 10.1177/2325967115625481. eCollection 2016 Jan.
- Background: PubMed 30300216Chu CR, Rodeo S, Bhutani N, Goodrich LR, Huard J, Irrgang J, LaPrade RF, Lattermann C, Lu Y, Mandelbaum B, Mao J, McIntyre L, Mishra A, Muschler GF, Piuzzi NS, Potter H, Spindler K, Tokish JM, Tuan R, Zaslav K, Maloney W. Optimizing Clinical Use of Biologics in Orthopaedic Surgery: Consensus Recommendations From the 2018 AAOS/NIH U-13 Conference. J Am Acad Orthop Surg. 2019 Jan 15;27(2):e50-e63. doi: 10.5435/JAAOS-D-18-00305.
- Background: PubMed 23997229Filardo G, Di Matteo B, Kon E, Dhillon MS, Patel S, Marwaha N. Platelet-rich plasma for knee osteoarthritis. Am J Sports Med. 2013 Sep;41(9):NP42-3. doi: 10.1177/0363546513502635. No abstract available.
- Background: PubMed 24189839Evans CH, Kraus VB, Setton LA. Progress in intra-articular therapy. Nat Rev Rheumatol. 2014 Jan;10(1):11-22. doi: 10.1038/nrrheum.2013.159. Epub 2013 Nov 5.
- Background: PubMed 15316121Garratt AM, Brealey S, Gillespie WJ; DAMASK Trial Team. Patient-assessed health instruments for the knee: a structured review. Rheumatology (Oxford). 2004 Nov;43(11):1414-23. doi: 10.1093/rheumatology/keh362. Epub 2004 Aug 17.
- Derived from this study: PubMed 40028743Dulic O, Abazovic D, Matijevic S, Rasovic P, Obradovic M, Bjelobrk M, Tosic M, Lalic I, Baljak B, Milinkov M. Quality of life changes in patients suffering from knee osteoarthritis treated with bone marrow aspirate concentrate, platelet-rich plasma and hyaluronic acid injections. Regen Med. 2025 Feb-Mar;20(2-3):87-96. doi: 10.1080/17460751.2025.2472589. Epub 2025 Mar 3.
- Derived from this study: PubMed 37577967Rasovic P, Dulic O, Lalic I, Matijevic R, Janjic N, Tosic M, Aleksandric D, Abazovic D, Miskulin M, Matijevic S, Kovacevic L. The role of osteoarthritis severity, BMI and age on clinical efficacy of bone marrow aspirate concentrate in the treatment of knee osteoarthritis. Regen Med. 2023 Sep;18(9):735-747. doi: 10.2217/rme-2023-0042. Epub 2023 Aug 14.
- Derived from this study: PubMed 33151802Dulic O, Lalic I, Kecojevic V, Gavrilovic G, Abazovic D, Miskulin M, Maric D, Bumbasirevic M. Do knee injection portals affect clinical results of bone marrow aspirate concentrate injection in the treatment of osteoarthritis? A prospective randomized controlled study. Regen Med. 2020 Aug;15(8):1987-2000. doi: 10.2217/rme-2020-0020. Epub 2020 Nov 5.
- Individual participant dataSharing planned: Yes. de-identified individual participant data for all primary and secondary outcome measures will be made available.
Related trials for Knee Osteoarthritis
Not yet recruiting
Holistic Healing for Knee Osteoarthritis
Knee Osteoarthritis (Knee OA)
Recruiting
Effect of Anti-inflammatory Diet in Osteoarthritis
Osteoarthritis, Knee
Active, not recruitingPhase 2/3
Single vs Triple Hyaluronic Acid in Knee Osteoarthritis
Osteoarthritis, Knee
Not yet recruiting
The Feasibility of a Virtual/Home-based OA Treatment Program in Older Adults With OA and Multimorbidity
Osteoarthritis of the Knee
RecruitingObservational study
Exploring Factors Linked to Worsening Over Time in People With Early-stage Knee Osteoarthritis and Those With Prior Proven Acute Knee Injury.
Knee Osteoarthritis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bone Marrow Aspirate Concentrate, Leukocyte Rich Platelet Rich Plasma and Hyaluronic Acid in people with Knee Osteoarthritis, run by Clinical Center of Vojvodina at 1 site in Serbia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change of WOMAC (time frame: after 1, 3, 6, 9 and 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03825133, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2019; AzTrials last refreshed its copy on 8 Nov 2026.