MEDICATION RELATED OSTEONECROSIS OF THE JAWPhase 1/2OZONE_EXONCT06072404
OZONE_EXO: Comparative Analysis of Protocols for Dental Exactions in Patients at Risk of MRONJ: Case-control Study
A Phase 1/2 study testing OxigenOzone_Insufflation in people with MEDICATION RELATED OSTEONECROSIS OF THE JAW, run by University of Palermo at 1 site in Italy.
Trial summary
Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is also a potentially painful and debilitating condition. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- MEDICATION RELATED OSTEONECROSIS OF THE JAW
- What is being tested?
- OxigenOzone_Insufflation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 1 siteItaly
- Study dates
- 1 Feb 2018to 30 Mar 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- age ≥ 18 yrs
- patients at risk of developing MRONJ for previous or current administration of drugs related
- extraction of teeth with a poor prognosis due to severe decay and/or periodontitis
Who cannot join
- previous radiation in the head and neck area
- neoplastic involvement of the jaw
- previous MRONJ diagnosis
Trial locations and contacts
1 site in 1 country.
Italy1 site
Azienda Ospedaliera Universitaria Policlinico "P. Giaccone" Palermo
Palermo, 90127
About this study
Official title: Comparative Analysis of Different Protocols for Dental Exactions in Patients at Risk of MRONJ: Case-control Study
Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is also a potentially painful and debilitating condition. Today, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established.
Among non-invasive procedures to treat MRONJ, the use of medical ozone (O3) arises for its properties and has been deployed and evaluated. O3 has generally proven to play a role in the treatment of chronic, nonhealing, or ischemic wounds, due to its antimicrobial and anti-oxidant properties and to bio-stimulation; it has been extensively used for different medical approaches and purposes. In oral cavity, local applications are carried out by ozonized water (i.e. spray or compress) or gel.
Read more
The aim of this study was to carry out a case-control study in order to compare two different protocols of dental extractions in patients at risk of MRONJ, with and without infiltration of a mixture of oxygen-ozone.
All the cases in our study are cancer and oncologic and osteometabolic patients undergoing high-risk therapy for MRONJ (antiresorptive and antiangiogenic drugs) who require dental extractions with a poor prognosis. During the first examination (T0), medical, pharmacological, and dental history of patients are recorded. Data collected are: (1) age; (2) gender; (3) indications for use, type, cumulative dose and duration of MRONJ-related drugs; (4); history of chemotherapy; (5) other medications; (6) other diseases; (7) smoking.
For each patient, an orthopantomography and a cone beam computed tomography of the teeth are performed only if indicated.
Read the detailed description
The enrolled patients were randomly divided into two groups:
Group A: consisting of 38 patients (undergoing ozone treatment) (OZONE_EXO) intra-tissutal perialveolar injections of a 15-mL mixture of OxigenOzone (O2O3) with a 26Gx1⁄2 - 0.45x13 mm needle and insufflation of the same mixture in the post-extraction site in patients at risk of medication-induced osteonecrosis of the jaw (ONJ).
Group B: comprising 79 controls (not undergoing ozone treatment).(NO_OZONE_EXO) Tooth extraction in patients at risk of medication-induced osteonecrosis of the jaw (ONJ) without the use of ozone application.
Following the same approach as in Group A, patients in Group B underwent additional follow-up visits at T1 (3-5 days), T2 (14 days), and T3 (6 weeks) post-extraction, in accordance with Inflammatory - P roliferative - Remodeling (IPR) Wound Healing Scale.
the IPR scale score, to meticulously monitor surgical wound healing and record pain intensity using the NRS scale, rather than the originally planned VAS scale, for enhanced ease of use [22].
The IPR scale provided a comprehensive assessment of wound healing through distinct subscales, each ranging from 0 to 1, resulting in a total score ranging from 0 to 16. These subscales evaluated the inflammatory response, proliferative response, and remodeling process. At the conclusion of the follow-up period, the total IPR score was computed, with scores spanning from 0 to 16. Scores of 0-4 denoted poor healings, scores of 5-10 indicated acceptable healing, while scores of 11-16 suggested excellent healing.
- Being tested
- OxigenOzone_Insufflation
- Keywords
- MRONJ, Osteonecrosis, Ozone therapy, Jaw, Antiresorptive, Antiangiogenic drugs, Adverse event
- Medical subject headings
- Osteonecrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxigenOzone_InsufflationBiological
intra-tissutal perialveolar injections of a 15-mL mixture of OxigenOzone (O2O3) with a 26Gx 1⁄2 - 0.45x13 mm needle and insufflation of the same mixture in the post-extraction site for at least 1 minute, hemostasis, and suture.
| Study group | Role | What they receive |
|---|---|---|
| Group A (OZONE_EXO) | Experimental | intra-tissutal perialveolar injections of a 15-mL mixture of OxigenOzone (O2O3) with a 26Gx1⁄2 - 0.45x13 mm needle and insufflation of the same mixture in the post-extraction site in patients at risk of medication-induced osteonecrosis of the jaw (ONJ). Receives: Biological: OxigenOzone_Insufflation |
| Group B (NO_OZONE_EXO) | No intervention | Tooth extraction in patients at risk of medication-induced osteonecrosis of the jaw (ONJ) without the use of ozone application. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Healing Evaluation Using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Inflammatory Phase
The inflammatory phase is evaluated 3-5 days after tissue injury on the basis of eight parameters, measured on a 9-point scale (0-8): bleeding (spontaneously or on palpation), granulation tissue, hematoma, tissue color, incision margins, suppuration, edema, and pain. A score of 5-8 indicates a successful inflammatory phase
Measured: 3-5 days after the intervention
Healing Evaluation Using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Proliferative Phase:
The proliferative phase is evaluated 14 days after tissue injury on the basis of five parameters, measured on a 6-point scale (0-5): re-epithelialization, tissue color, scar, suppuration, and pain. A score of 3-5 score indicates successful healing.
Measured: 14 days after the intervention
Healing Evaluation Using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Remodelling Phase
The remodeling phase is evaluated 6 weeks after tissue injury on the basis of three parameters, measured on a 4-point scale (0-3): scar, tissue color, and pain. A score of 2-3 indicates successful healing
Measured: 6 weeks after the intervention
Secondary outcomes (1)
Healing Evaluation Using IPR Scale: Total Process
The total score of the IPR scale ranges from 0 to 16:0-4 indicates poor healing; 5-10, acceptable healing; and 11-16, excellent healing The inflammatory phase carries the greatest weight in the final score because its impairment can jeopardize the entire series of biologic events leading to early wound healing.
Measured: 6 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start1 Feb 2018
- Primary completion30 Mar 2020
- Study completion30 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for MEDICATION RELATED OSTEONECROSIS OF THE JAWStudies 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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Palermo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Olga Di Fede, University of Palermo
- Investigators
- Olga Di Fede, Professor, Principal investigator, University of Palermo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06072404
- Sponsor's protocol ID
- OZONE_EXO
- Acronym
- OZONE_EXO
- Status last verified
- Dec 2024
- First submitted
- 27 Sep 2023
- Last updated
- 9 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Campisi G, Mauceri R, Bertoldo F, Bettini G, Biasotto M, Colella G, Consolo U, Di Fede O, Favia G, Fusco V, Gabriele M, Lo Casto A, Lo Muzio L, Marciano A, Mascitti M, Meleti M, Mignogna MD, Oteri G, Panzarella V, Romeo U, Santarelli A, Vescovi P, Marchetti C, Bedogni A. Medication-Related Osteonecrosis of Jaws (MRONJ) Prevention and Diagnosis: Italian Consensus Update 2020. Int J Environ Res Public Health. 2020 Aug 18;17(16):5998. doi: 10.3390/ijerph17165998.
PubMed 32824826Oldoini G, Frabattista GR, Saragoni M, Cosola S, Giammarinaro E, Genovesi AM, Marconcini S. Ozone Therapy for Oral Palatal Ulcer in a Leukaemic Patient. Eur J Case Rep Intern Med. 2020 Jan 14;7(2):001406. doi: 10.12890/2020_001406. eCollection 2020.
PubMed 32133312Palma LF, Joia C, Chambrone L. Effects of ozone therapy on periodontal and peri-implant surgical wound healing: a systematic review. Quintessence Int. 2023 Feb 10;54(2):100-110. doi: 10.3290/j.qi.b3512007.
PubMed 36437805Agrillo A, Ungari C, Filiaci F, Priore P, Iannetti G. Ozone therapy in the treatment of avascular bisphosphonate-related jaw osteonecrosis. J Craniofac Surg. 2007 Sep;18(5):1071-5. doi: 10.1097/scs.0b013e31857261f.
PubMed 17912085
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Analysis of Different Protocols for Dental Exactions in Patients at Risk of MRONJ: Case-control Study
- ClinicalTrials.gov ID
- NCT06072404
- Acronym / sponsor ID
- OZONE_EXO / OZONE_EXO
- Keywords
- MRONJ, Osteonecrosis, Ozone therapy, Jaw, Antiresorptive, Antiangiogenic drugs, Adverse event
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- University of PalermoUniversity, hospital or other
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 30 Mar 2020 (actual)
- Study completion
- 30 Mar 2020 (actual)
- First posted
- 10 Oct 2023 (actual)
- Results
- Posted 9 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is also a potentially painful and debilitating condition. Today, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established.
Among non-invasive procedures to treat MRONJ, the use of medical ozone (O3) arises for its properties and has been deployed and evaluated. O3 has generally proven to play a role in the treatment of chronic, nonhealing, or ischemic wounds, due to its antimicrobial and anti-oxidant properties and to bio-stimulation; it has been extensively used for different medical approaches and purposes. In oral cavity, local applications are carried out by ozonized water (i.e. spray or compress) or gel.
The aim of this study was to carry out a case-control study in order to compare two different protocols of dental extractions in patients at risk of MRONJ, with and without infiltration of a mixture of oxygen-ozone.
All the cases in our study are cancer and oncologic and osteometabolic patients undergoing high-risk therapy for MRONJ (antiresorptive and antiangiogenic drugs) who require dental extractions with a poor prognosis. During the first examination (T0), medical, pharmacological, and dental history of patients are recorded. Data collected are: (1) age; (2) gender; (3) indications for use, type, cumulative dose and duration of MRONJ-related drugs; (4); history of chemotherapy; (5) other medications; (6) other diseases; (7) smoking.
For each patient, an orthopantomography and a cone beam computed tomography of the teeth are performed only if indicated.
Detailed description
The enrolled patients were randomly divided into two groups:
Group A: consisting of 38 patients (undergoing ozone treatment) (OZONE_EXO) intra-tissutal perialveolar injections of a 15-mL mixture of OxigenOzone (O2O3) with a 26Gx1⁄2 - 0.45x13 mm needle and insufflation of the same mixture in the post-extraction site in patients at risk of medication-induced osteonecrosis of the jaw (ONJ).
Group B: comprising 79 controls (not undergoing ozone treatment).(NO_OZONE_EXO) Tooth extraction in patients at risk of medication-induced osteonecrosis of the jaw (ONJ) without the use of ozone application.
Following the same approach as in Group A, patients in Group B underwent additional follow-up visits at T1 (3-5 days), T2 (14 days), and T3 (6 weeks) post-extraction, in accordance with Inflammatory - P roliferative - Remodeling (IPR) Wound Healing Scale.
the IPR scale score, to meticulously monitor surgical wound healing and record pain intensity using the NRS scale, rather than the originally planned VAS scale, for enhanced ease of use [22].
The IPR scale provided a comprehensive assessment of wound healing through distinct subscales, each ranging from 0 to 1, resulting in a total score ranging from 0 to 16. These subscales evaluated the inflammatory response, proliferative response, and remodeling process. At the conclusion of the follow-up period, the total IPR score was computed, with scores spanning from 0 to 16. Scores of 0-4 denoted poor healings, scores of 5-10 indicated acceptable healing, while scores of 11-16 suggested excellent healing.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A (OZONE_EXO) | Experimental | Biological: OxigenOzone_Insufflationintra-tissutal perialveolar injections of a 15-mL mixture of OxigenOzone (O2O3) with a 26Gx1⁄2 - 0.45x13 mm needle and insufflation of the same mixture in the post-extraction site in patients at risk of medication-induced osteonecrosis of the jaw (ONJ). |
| Group B (NO_OZONE_EXO) | No intervention | –Tooth extraction in patients at risk of medication-induced osteonecrosis of the jaw (ONJ) without the use of ozone application. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- age ≥ 18 yrs
- patients at risk of developing MRONJ for previous or current administration of drugs related
- extraction of teeth with a poor prognosis due to severe decay and/or periodontitis
Key exclusion criteria (3 listed)
- previous radiation in the head and neck area
- neoplastic involvement of the jaw
- previous MRONJ diagnosis
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 |
|---|---|---|
| OxigenOzone_Insufflationintra-tissutal perialveolar injections of a 15-mL mixture of OxigenOzone (O2O3) with a 26Gx 1⁄2 - 0.45x13 mm needle and insufflation of the same mixture in the post-extraction site for at least 1 minute, hemostasis, and suture. | Biological | Group A (OZONE_EXO) |
Primary outcome
Healing Evaluation Using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Inflammatory Phase
Time frame: 3-5 days after the intervention
The inflammatory phase is evaluated 3-5 days after tissue injury on the basis of eight parameters, measured on a 9-point scale (0-8): bleeding (spontaneously or on palpation), granulation tissue, hematoma, tissue color, incision margins, suppuration, edema, and pain. A score of 5-8 indicates a successful inflammatory phase
Healing Evaluation Using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Proliferative Phase:
Time frame: 14 days after the intervention
The proliferative phase is evaluated 14 days after tissue injury on the basis of five parameters, measured on a 6-point scale (0-5): re-epithelialization, tissue color, scar, suppuration, and pain. A score of 3-5 score indicates successful healing.
Healing Evaluation Using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Remodelling Phase
Time frame: 6 weeks after the intervention
The remodeling phase is evaluated 6 weeks after tissue injury on the basis of three parameters, measured on a 4-point scale (0-3): scar, tissue color, and pain. A score of 2-3 indicates successful healing
1 secondary outcome
Healing Evaluation Using IPR Scale: Total Process
Time frame: 6 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32824826Campisi G, Mauceri R, Bertoldo F, Bettini G, Biasotto M, Colella G, Consolo U, Di Fede O, Favia G, Fusco V, Gabriele M, Lo Casto A, Lo Muzio L, Marciano A, Mascitti M, Meleti M, Mignogna MD, Oteri G, Panzarella V, Romeo U, Santarelli A, Vescovi P, Marchetti C, Bedogni A. Medication-Related Osteonecrosis of Jaws (MRONJ) Prevention and Diagnosis: Italian Consensus Update 2020. Int J Environ Res Public Health. 2020 Aug 18;17(16):5998. doi: 10.3390/ijerph17165998.
- Background: PubMed 32133312Oldoini G, Frabattista GR, Saragoni M, Cosola S, Giammarinaro E, Genovesi AM, Marconcini S. Ozone Therapy for Oral Palatal Ulcer in a Leukaemic Patient. Eur J Case Rep Intern Med. 2020 Jan 14;7(2):001406. doi: 10.12890/2020_001406. eCollection 2020.
- Background: PubMed 36437805Palma LF, Joia C, Chambrone L. Effects of ozone therapy on periodontal and peri-implant surgical wound healing: a systematic review. Quintessence Int. 2023 Feb 10;54(2):100-110. doi: 10.3290/j.qi.b3512007.
- Background: PubMed 17912085Agrillo A, Ungari C, Filiaci F, Priore P, Iannetti G. Ozone therapy in the treatment of avascular bisphosphonate-related jaw osteonecrosis. J Craniofac Surg. 2007 Sep;18(5):1071-5. doi: 10.1097/scs.0b013e31857261f.
- Individual participant dataSharing planned: No
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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.
Olga Di Fede, Professor principal investigator
University of Palermo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing OxigenOzone_Insufflation in people with MEDICATION RELATED OSTEONECROSIS OF THE JAW, run by University of Palermo 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 3 inclusion and 3 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 9 Jan 2025. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Healing Evaluation Using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Inflammatory Phase (time frame: 3-5 days after the intervention). The study lists 3 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 NCT06072404, which also lists 4 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 9 Jan 2025.