Clinical trial NCT06072404: OZONE_EXO: Comparative Analysis of Protocols for Dental Exactions in Patients at Risk of MRONJ: Case-control Study
Official title: Comparative Analysis of Different Protocols for Dental Exactions in Patients at Risk of MRONJ: Case-control Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: MEDICATION RELATED OSTEONECROSIS OF THE JAW
Keywords: MRONJ
Osteonecrosis
Ozone therapy
Jaw
Antiresorptive
Antiangiogenic drugs
Adverse event
Lead sponsor: University of Palermo
Sponsor class: OTHER
First posted: 2023-10-10
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* previous radiation in the head and neck area
* neoplastic involvement of the jaw
* previous MRONJ diagnosis

Primary outcomes:
measure: Healing Evaluation Using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Inflammatory Phase
timeFrame: 3-5 days after the intervention
measure: Healing Evaluation Using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Proliferative Phase:
timeFrame: 14 days after the intervention
measure: Healing Evaluation Using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Remodelling Phase
timeFrame: 6 weeks after the intervention
Secondary outcomes:
measure: Healing Evaluation Using IPR Scale: Total Process
timeFrame: 6 week
Other outcomes:
Locations:
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico "P. Giaccone" Palermo
Study officials:
affiliation: University of Palermo
name: Olga Di Fede, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Oldoini 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.
citation: Palma 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.
citation: Agrillo 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.