Knee OsteoarthritisPhase 3NCT04426721
Intra-articular Oxygen-ozone Therapy for the Treatment of Knee Osteoarthritis Compared With Hyaluronic Acid
A Phase 3 study testing Ozone and Hyaluronic Acid in people with Knee Osteoarthritis, run by Humanitas Clinical and Research Center at 1 site in Italy.
Trial summary
Knee osteoarthritis is a very common pathology, characterized by pain, stiffness and functional deficit. The various therapeutic options used include anti-inflammatory drug treatment, physiokinesitherapy, minimally invasive procedures and, finally, in non-responsive cases, surgical treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- Ozone and Hyaluronic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2020to Dec 2022
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female at least 18 years of age at time of screening.
- Ability to comply with study procedures and visit schedules and able to follow oral and written instructions.
- Patients with symptomatic OA in one knee from 3 months
- A standing knee radiograph showing a K-L grade of 2 to 3 and an absence of severe osteoarthritis (defined as advanced stage osteoarthritis, including large osteophytes, chronic fractures or bone remodeling, severe deformity or bone attrition, and/or bone-on-bone contact indicative of severe osteoarthritis/full thickness cartilage loss).
- Body mass index ≤ 40 kg/m2.
- A WOMAC LK 3.1 pain subscale total score ≥ 9 and ≤ 19.
- Has undergone at least one prior conservative OA treatment (e.g. physical therapy, simple analgesics).
- Signed an ethics committee-reviewed an approved informed consent form.
Who cannot join
- Presence of clinically observed active infection or severe inflammation in the index knee joint or skin disease/breakdown or infection in the area of the planned injection site of the index knee.
- Presence of symptomatic OA in the non-study knee at screening; if unclear then the WOMAC LK 3.1 pain subscale for the non-index knee must be ≤ 5.0.
- Diagnosed with rheumatoid arthritis, Reiter's syndrome, psoriatic arthritis, gout, ankylosing spondylitis, or arthritis secondary to other inflammatory diseases; Human Immunodeficiency Virus (HIV), viral hepatitis; chondrocalcinosis, Paget's disease, or villonodular synovitis.
- Diagnosed with leukemia, known presence of metastatic malignant cells, or ongoing or planned chemotherapeutic treatment.
- Disease of spine, hip or other lower extremity joints judged by the investigator to be contributing to the pain in the index knee (e.g. sciatica, nerve pain, hip OA). Note: Patients with contralateral knee replacement, or hip replacement in either hip, may be enrolled provided there is sufficient pain relief after knee replacement or hip replacement that analgesics are not required.
- Untreated symptomatic injury of the index knee (e.g., acute traumatic injury, anterior cruciate ligament injury, clinically symptomatic meniscus injury characterized by mechanical issue such as locking or catching).
Show all 19Show fewer
- Presence of surgical hardware or other foreign body intended to treat arthritis or cartilage-related pathology in the index knee. Note: this does not include small hardware (e.g. screws).
- Presence of venous or lymphatic stasis in the index leg.
- Orally administered systemic steroid use within 2 weeks prior to screening
- Planned/anticipated surgery of the index knee during the study period.
- Major surgery of the index knee within 12 months prior to screening.
- Minor surgery (e.g. arthroscopy) of the index knee within 6 months prior to screening.
- Any documented clinically significant degree of cognitive impairment or other condition, finding, or psychiatric illness at screening, which, in the opinion of the investigator, could compromise patient safety or interfere with the assessment of the safety and treatment effects of the study injection.
- Pregnant or nursing mothers or women planning to become pregnant during the time they will be participating in the study.
- Know hypersensitivity (allergy) to hyaluronan (sodium hyaluronate) preparations.
- Previously documented failed treatment with OOT or Sinovial
- Known drug or alcohol dependence currently or within the last year.
- Use of any investigational drug or device within 30 days prior to screening.
- Use of any investigational biologics within 60 days prior to screening.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Humanitas Clinical and Research Hospital
Rozzano, Milano, 20089
Cristiano Sconza, MD, 3332781989, cristiano.sconza@humanitas.it
Roberta Amenta, MD, 3286935530, roberta8928@gmail.com
About this study
Official title: Intra-articular Oxygen-ozone Therapy for the Treatment of Knee Osteoarthritis: a Randomized, Double-blind, Clinical Trial Compared With Hyaluronic Acid
Knee osteoarthritis is a very common pathology, characterized by pain, stiffness and functional deficit. The various therapeutic options used include anti-inflammatory drug treatment, physiokinesitherapy, minimally invasive procedures and, finally, in non-responsive cases, surgical treatment. To date, several studies have been conducted on the intra-articular use of oxygen-ozone in knee osteoarthritis and its potential therapeutic benefits. However, the methodological quality of the RCTs available in the literature is not satisfactory, so it is necessary to define a standardized protocol for therapy and procedures. The aim of this study will be to develop a rigorous protocol to evaluate the effectiveness of intra-articular oxygen-ozone therapy (OOT) in knee osteoarthritis and compare it with injection therapy with hyaluronic acid (HA), currently widely used in the treatment of knee osteoarthritis.
Read the detailed description
Osteoarthritis is a degenerative condition that causes pain, impaired function and affects daily activities. In knee osteoarthritis, there is destruction of cartilage and subchondral bone, with the consequent narrowing of articular space. Besides the biomechanical factors, trauma and obesity; it is believed that inflammation plays an important role. Treatment options for painful knee osteoarthritis are often unsatisfactory, as represented by 40% of patients reporting persisting postoperative pain following total knee arthroplasty . There are no currently approved knee osteoarthritis treatments capable of slowing OA-related structural progression, so the main goals of the conservative treatment are to provide symptomatic relief, improve joint function, and delay surgical intervention. One of the main actions of intra-articular treatments, ranging from corticosteroids to hyaluronic acid (HA) and biologic products is to reduce inflammatory distress within the joint. In recent years, there has been a growing interest in the effects of ozone, which can be safely delivered intra-articularly and whose use is in constant increase in an outpatient setting due to the ease of preparation methods. From the literature, it is widely accepted that ozone has the biological properties of inducing analgesia, anti-inflammatory, and antioxidant effects mediated by activating the cellular metabolism and inhibiting prostaglandin synthesis, reduce edema and inflammation, and therefore reduce pain and improves function in knee osteoarthritis. Intra-articular oxygen-ozone has been used in the medical domain for several decades. Although some articles have reported promising results on the effectiveness of oxygen-ozone in knee osteoarthritis, the evidence is however low . Currently, few RCTs have compared the efficacy and safety of ozone therapy versus HA intra-articular injections in patients affected by knee osteoarthritis. This study will compare the efficacy of OOT injection to HA in patients with symptomatic OA in one knee, who have failed at least one prior conservative OA therapy (e.g. physiotherapy, simple analgesics). This will be done using a double blind, randomized controlled trial with study subjects receiving a cycle of three injection of OOT or HA. The primary efficacy measure will be pain measured by the WOMAC LK 3.1 scale; other measures of efficacy will include function, stiffness, and quality of life. In addition to clinical efficacy measures, safety will be assessed by tracking adverse events. During screening, potential subjects who provide informed consent will be assessed for eligibility. Screening will consist in checking the presence of inclusion and exclusion criteria, including a WOMAC LK 3.1 pain subscale score ≥ 9 and ≤ 19 and by providing objective physiological evidence of OA using the Kellgren-Lawrence scale (assessed from radiographs). Subjects will also provide demographic and medication use information. Baseline X-ray and MRI will be collected.
- Conditions
- Knee Osteoarthritis
- Being tested
- Ozone, Hyaluronic Acid
- Keywords
- Oxygene-Ozone, Ozone, Hyaluronic acid, Osteoarthritis
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OzoneDrug
Also called Oxygene-Ozone therapy; O2-O3
10 cc of oxygen-ozone
Hyaluronic AcidDrug
Also called Sinovial forte
Sinovial forte 32 mg\2ml
| Study group | Role | What they receive |
|---|---|---|
| Ozone | Experimental | Participant will receive an intraarticular injection of oxygen-ozone, once a week for three weeks. During procedure a clear ultrasound image is to be taken to document needle placement in the synovial space. The injector may choose the position of the knee (e.g., extended or bent) and the approach for the injection (e.g., medial or lateral). Receives: Drug: Ozone |
| Hyaluronic acid | Active comparator | Participant will receive an intraarticular injection of hyaluronic acid, once a week for three weeks. During procedure a clear ultrasound image is to be taken to document needle placement in the synovial space. The injector may choose the position of the knee (e.g., extended or bent) and the approach for the injection (e.g., medial or lateral). Receives: Drug: Hyaluronic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Western Ontario and McMaster Universities Osteoarthritis Index using the Likert scale, Version 3.1, Pain subscale (WOMAC LK 3.1)
Assessment of pain. Score range 0-20. Higher scores indicate worse pain.
Measured: 3 months
Secondary outcomes (3)
The Western Ontario and McMaster Universities Osteoarthritis Index using the Likert scale, Version 3.1(WOMAC LK 3.1)
Assessment of pain, stiffness and function. Score range 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. Higher scores indicate worse pain, stiffness, and functional limitations.
Measured: 1,3,6,12 months
Numeric Rating Scale (NRS)
Assessment of pain. Score range 0-10. Higher scores indicate worse pain.
Measured: 1,3,6,12 months
Knee Injury and Osteoarthritis Outcome Score (KOOS)
Assessment of Pain, other Symptoms, Function in daily living, Function in Sport and Recreation, and knee-related Quality of Life (QOL). Score range 0-100, with zero representing extreme knee problems and 100 representing no knee problems
Measured: 1,3,6,12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study startJun 2020 (estimated)
- Primary completionDec 2021 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Humanitas Clinical and Research Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cristiano Sconza, Humanitas Clinical and Research Center
- Investigators
- Cristiano Sconza, MD, Principal investigator, Humanitas Clinical and Research HospitalBerardo Di Matteo, MD, PhD, Study chair, Humanitas Clinical and Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04426721
- Sponsor's protocol ID
- OZKOA1
- Status last verified
- Jun 2020
- First submitted
- 8 Jun 2020
- Last updated
- 16 Jun 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intra-articular Oxygen-ozone Therapy for the Treatment of Knee Osteoarthritis: a Randomized, Double-blind, Clinical Trial Compared With Hyaluronic Acid
- ClinicalTrials.gov ID
- NCT04426721
- Acronym / sponsor ID
- OZKOA1
- Conditions
- Knee Osteoarthritis
- Keywords
- Oxygene-Ozone, Ozone, Hyaluronic acid, Osteoarthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Humanitas Clinical and Research CenterUniversity, hospital or other
- Study start
- Jun 2020 (estimated)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 11 Jun 2020 (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.
Knee osteoarthritis is a very common pathology, characterized by pain, stiffness and functional deficit. The various therapeutic options used include anti-inflammatory drug treatment, physiokinesitherapy, minimally invasive procedures and, finally, in non-responsive cases, surgical treatment. To date, several studies have been conducted on the intra-articular use of oxygen-ozone in knee osteoarthritis and its potential therapeutic benefits. However, the methodological quality of the RCTs available in the literature is not satisfactory, so it is necessary to define a standardized protocol for therapy and procedures. The aim of this study will be to develop a rigorous protocol to evaluate the effectiveness of intra-articular oxygen-ozone therapy (OOT) in knee osteoarthritis and compare it with injection therapy with hyaluronic acid (HA), currently widely used in the treatment of knee osteoarthritis.
Detailed description
Osteoarthritis is a degenerative condition that causes pain, impaired function and affects daily activities. In knee osteoarthritis, there is destruction of cartilage and subchondral bone, with the consequent narrowing of articular space. Besides the biomechanical factors, trauma and obesity; it is believed that inflammation plays an important role. Treatment options for painful knee osteoarthritis are often unsatisfactory, as represented by 40% of patients reporting persisting postoperative pain following total knee arthroplasty . There are no currently approved knee osteoarthritis treatments capable of slowing OA-related structural progression, so the main goals of the conservative treatment are to provide symptomatic relief, improve joint function, and delay surgical intervention. One of the main actions of intra-articular treatments, ranging from corticosteroids to hyaluronic acid (HA) and biologic products is to reduce inflammatory distress within the joint. In recent years, there has been a growing interest in the effects of ozone, which can be safely delivered intra-articularly and whose use is in constant increase in an outpatient setting due to the ease of preparation methods. From the literature, it is widely accepted that ozone has the biological properties of inducing analgesia, anti-inflammatory, and antioxidant effects mediated by activating the cellular metabolism and inhibiting prostaglandin synthesis, reduce edema and inflammation, and therefore reduce pain and improves function in knee osteoarthritis. Intra-articular oxygen-ozone has been used in the medical domain for several decades. Although some articles have reported promising results on the effectiveness of oxygen-ozone in knee osteoarthritis, the evidence is however low . Currently, few RCTs have compared the efficacy and safety of ozone therapy versus HA intra-articular injections in patients affected by knee osteoarthritis. This study will compare the efficacy of OOT injection to HA in patients with symptomatic OA in one knee, who have failed at least one prior conservative OA therapy (e.g. physiotherapy, simple analgesics). This will be done using a double blind, randomized controlled trial with study subjects receiving a cycle of three injection of OOT or HA. The primary efficacy measure will be pain measured by the WOMAC LK 3.1 scale; other measures of efficacy will include function, stiffness, and quality of life. In addition to clinical efficacy measures, safety will be assessed by tracking adverse events. During screening, potential subjects who provide informed consent will be assessed for eligibility. Screening will consist in checking the presence of inclusion and exclusion criteria, including a WOMAC LK 3.1 pain subscale score ≥ 9 and ≤ 19 and by providing objective physiological evidence of OA using the Kellgren-Lawrence scale (assessed from radiographs). Subjects will also provide demographic and medication use information. Baseline X-ray and MRI will be collected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ozone | Experimental | Drug: OzoneParticipant will receive an intraarticular injection of oxygen-ozone, once a week for three weeks. During procedure a clear ultrasound image is to be taken to document needle placement in the synovial space. The injector may choose the position of the knee (e.g., extended or bent) and the approach for the injection (e.g., medial or lateral). |
| Hyaluronic acid | Active comparator | Drug: Hyaluronic AcidParticipant will receive an intraarticular injection of hyaluronic acid, once a week for three weeks. During procedure a clear ultrasound image is to be taken to document needle placement in the synovial space. The injector may choose the position of the knee (e.g., extended or bent) and the approach for the injection (e.g., medial or lateral). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female at least 18 years of age at time of screening.
- Ability to comply with study procedures and visit schedules and able to follow oral and written instructions.
- Patients with symptomatic OA in one knee from 3 months
- A standing knee radiograph showing a K-L grade of 2 to 3 and an absence of severe osteoarthritis (defined as advanced stage osteoarthritis, including large osteophytes, chronic fractures or bone remodeling, severe deformity or bone attrition, and/or bone-on-bone contact indicative of severe osteoarthritis/full thickness cartilage loss).
- Body mass index ≤ 40 kg/m2.
Key exclusion criteria (19 listed)
- Presence of clinically observed active infection or severe inflammation in the index knee joint or skin disease/breakdown or infection in the area of the planned injection site of the index knee.
- Presence of symptomatic OA in the non-study knee at screening; if unclear then the WOMAC LK 3.1 pain subscale for the non-index knee must be ≤ 5.0.
- Diagnosed with rheumatoid arthritis, Reiter's syndrome, psoriatic arthritis, gout, ankylosing spondylitis, or arthritis secondary to other inflammatory diseases; Human Immunodeficiency Virus (HIV), viral hepatitis; chondrocalcinosis, Paget's disease, or villonodular synovitis.
- Diagnosed with leukemia, known presence of metastatic malignant cells, or ongoing or planned chemotherapeutic treatment.
- Disease of spine, hip or other lower extremity joints judged by the investigator to be contributing to the pain in the index knee (e.g. sciatica, nerve pain, hip OA). Note: Patients with contralateral knee replacement, or hip replacement in either hip, may be enrolled provided there is sufficient pain relief after knee replacement or hip replacement that analgesics are not required.
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 |
|---|---|---|
| OzoneAlso: Oxygene-Ozone therapy; O2-O310 cc of oxygen-ozone | Drug | Ozone |
| Hyaluronic AcidAlso: Sinovial forteSinovial forte 32 mg\2ml | Drug | Hyaluronic acid |
Primary outcome
Western Ontario and McMaster Universities Osteoarthritis Index using the Likert scale, Version 3.1, Pain subscale (WOMAC LK 3.1)
Time frame: 3 months
Assessment of pain. Score range 0-20. Higher scores indicate worse pain.
3 secondary outcomes
The Western Ontario and McMaster Universities Osteoarthritis Index using the Likert scale, Version 3.1(WOMAC LK 3.1)
Time frame: 1,3,6,12 months
Numeric Rating Scale (NRS)
Time frame: 1,3,6,12 months
Knee Injury and Osteoarthritis Outcome Score (KOOS)
Time frame: 1,3,6,12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Individual participant dataSharing planned: Undecided
Related trials for Knee Osteoarthritis
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
Holistic Healing for Knee Osteoarthritis
Knee Osteoarthritis (Knee OA)
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
Not yet recruiting
The Feasibility of a Virtual/Home-based OA Treatment Program in Older Adults With OA and Multimorbidity
Osteoarthritis of the Knee
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.
Cristiano Sconza, MD principal investigator
Humanitas Clinical and Research Hospital
Berardo Di Matteo, MD, PhD study chair
Humanitas Clinical and Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ozone and Hyaluronic Acid in people with Knee Osteoarthritis, run by Humanitas Clinical and Research Center at 1 site in Italy.
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 8 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 16 Jun 2020. 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 Italy. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cristiano Sconza, MD (3332781989 ext. 0039, cristiano.sconza@humanitas.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Western Ontario and McMaster Universities Osteoarthritis Index using the Likert scale, Version 3.1, Pain subscale (WOMAC LK 3.1) (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jun 2020; AzTrials last refreshed its copy on 7 Nov 2026.