Impacted Mandibular Third Molar ExtractionPhase 3NCT06802354
Efficacy of Ozone Therapy in Reducing Complications Following Impacted Mandibular Third-molar Surgery
A Phase 3 study testing Ozone in people with Impacted Mandibular Third Molar Extraction, run by Jelena Krunic at 1 site in Bosnia and Herzegovina.
Trial summary
The goal of this clinical trial is to learn if use of ozone works to treat complications after impacted mandibular third molar surgery. It will also learn does ozone has positive effect on wound healing and quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Impacted Mandibular Third Molar Extraction
- What is being tested?
- Ozone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteBosnia and Herzegovina
- Study dates
- 1 Dec 2024to 15 Dec 2025
- 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
- Patients over 18 years
- Patients with bilaterally impacted mandibular third molars classified as impaction index II B
- Patients in good general health (based on the ASA classification as ASA I and ASA II).
Who cannot join
- Contraindications for ozone application (pregnancy, hyperthyroidism, favism, anemia, myasthenia, bleeding disorders, alcohol intoxication, myocardial infarction, pacemaker, allergy to ozone)
- Patients who have used corticosteroid and antibiotic therapy in the last three months prior to inclusion in the study
- Patients with signs of local inflammation in the oral cavity
- Female patients during pregnancy and breastfeeding.
Trial locations and contacts
1 site in 1 country.
Bosnia and Herzegovina1 site
University of East Sarajevo, Faculty of Medicine
Foca, Republika Srpska, 73300
About this study
Official title: Application of Gaseous Ozone in the Surgical Extraction of Impacted Mandibular Third Molars: Impact on the Incidence of Postoperative Complications and Healing Processes
The goal of this clinical trial is to learn if use of ozone works to treat complications after impacted mandibular third molar surgery. It will also learn does ozone has positive effect on wound healing and quality of life.
The main questions it aims to answer are:
Read more
- Does ozone reduce incidence of postoperative compliactions such as pain, swelling or reduced mouth opening after impacted mandibular third molar surgery?
- Does ozone improve wound healing after impacted mandibular third molar surgery?
- Does ozone have positive effect on quality of life after impacted mandibular third molar surgery?
Participants will:
- Receive ozone after impacted mandibular third molar surgery.
- Visit the clinic 1st, 3rd, and 7th days after the intervention for checkups and tests.
- Keep a diary of their symptoms.
Read the detailed description
The aims of this study were: (i) to determine the effects of gaseous ozone on pain, swelling, and trismus and healing process measured by cytokine levels, and (ii) to measure patient quality of life after impacted mandibular third molar surgery.
All participants included in the study will be informed about the aims and expected outcomes of the research, the sample collection procedure, and will sign an informed consent form. All participants will be treated according to the principles of good clinical practice and in accordance with the Helsinki Declaration. The Ethics Committee of the Faculty of Medicine provide study approval.
The surgical procedure for each patient will be performed using a standardized surgical technique in two clinical visits (one side per visit).
The surgical area will be disinfected. To ensure pain relief during the procedure, local anesthesia will be applied using blocks of the inferior alveolar and buccal nerves. After elevating the flap, osteotomy will be performed with a carbide drill using an air drill and continuous irrigation with saline solution. Depending on the morphology of the tooth, the third molar will either be extracted or the crown will be separated from the roots (separation). The wound will be primarily closed with individual sutures, and the sutures will be removed on the seventh postoperative day. After the surgical extraction of the third molar belonging the ozone therapy group, gaseous ozone will be applied to the extraction wound. Ozone will be reapplied 3 days after the intervention. After the surgical extraction of the third molar assigned to the sham ozone therapy, ozone will be applied by placing an inactive AV probe at the extraction site. The sham ozone therapy will also be applied 3 days after the surgical intervention. Postoperative instructions will be given to participants regarding oral hygiene maintenance, the use of cold compresses, and dietary recommendations. All participants will be invited for follow-up examinations on the 1st, 3rd and 7th day after the intervention.
Statistical data analysis will be conducted using SPSS version 20.0 (IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp, USA). Normality testing will be performed, and depending on the results, parametric and/or non-parametric tests will be applied. To compare differences between groups, chi-square tests, independent t-tests, and/or Mann-Whitney tests will be used. To determine differences within groups, paired t-tests and/or Wilcoxon tests will be applied. The correlation between variables will be determined using Pearson or Spearman correlation. A p-value of <0.05 will be considered statistically significant in all analyses.
- Being tested
- Ozone, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OzoneDrug
In Ozone group, ozone will be applied at the site of the extraction wound for 30 seconds after the surgical extraction of the third molar, according to the manufacturer's recommendation for wound treatment following tooth extraction.
PlaceboDrug
In the control group, a sham ozone therapy will be applied at the site of the extraction wound for 30 seconds after the surgical extraction of the third molar .
| Study group | Role | What they receive |
|---|---|---|
| Ozone therapy | Experimental | After the surgical extraction of the impacted mandibular third molar, gaseous ozone will be applied at the extraction site. Ozone will be reapplied 3 days after the intervention, according to the manufacturer's recommendation for wound treatment following tooth extraction. Receives: Drug: Ozone |
| Sham Comparator | Sham comparator | After the surgical extraction of the impacted mandibular third molar, a sham ozone therapy will be applied at the extraction site. The sham ozone therapy will also be reapplied 3 days after the surgical intervention. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative complication: pain
For the assessment of postoperative pain, the Numeric Visual Analogue Scale (VAS) (Carlsson, 1983) and the Verbal Rating Scale (VRS) (Aitken et al., 1969) will be used, which patients will complete. VAS is a horizontally drawn line of 100 mm in length, where the left end represents the absence of pain (0 mm), and the right end (100 mm) represents the worst pain ever experienced. The pain intensity will be determined by measuring the distance from the marked point on the scale to the left side of the scale and expressed in millimeters. The VRS is a numerical assessment of pain intensity based on six levels: 1 - no pain, 2 - very mild pain, 3 - mild pain, 4 - moderate pain, 5 - severe pain, 6 - very severe pain.
Measured: 1st, 3rd, and 7th days after the intervention
Postoperative complication: trismus
The degree of postoperative trismus will be assessed by measuring the distance between the mesio-incisal angles of the upper and lower central incisors with the mouth fully open, using a caliper. The value will be expressed in millimeters (Marković and Todorović, 2007).
Measured: 1st, 3rd, and 7th days after the intervention
Postoperative complication: swelling
The assessment of postoperative swelling will be performed by calculating the postoperative edema coefficient (Ec) using the modified formula by Carrillo et al. (1990): Postoperative distance - Preoperative distance x 100 /Preoperative distance. The postoperative Ec will be obtained by measuring in millimeters the preoperative and postoperative distances between the following reference points (R): AC - the most posterior point on the tragus to the lateral point at the corner of the mouth, AD - the most posterior point on the tragus to the prominent soft tissue landmark and BE - the lateral canthus of the eye to the lowest point on the angle of the mandible. Measurement will be done with a flexible ruler just before the intervention (the baseline value used for evaluating subsequent values).
Measured: 1st, 3rd, and 7th days after the intervention
Cytokine levels- wound healing
To determine the expression of IL-1β, IL-6, IL-8, TNF-α, VEGF, and TGF-β in samples from extraction wounds, real-time polymerase chain reaction (qPCR) will be used. Gene expression will be determined using "housekeeping" genes as standards and appropriate primers, according to the manufacturer's instructions. Each sample will be analyzed in duplicate.
Measured: After surgical intervention, 3rd and 7th days after the intervention
Secondary outcomes (1)
Measurement of Quality of life of patients using The Oral Health Impact Profile - 14 (OHIP-14) before and 7th day after surgical intervention
The Oral Health Impact Profile - 14 (Locker, 1998) will be used to assess quality of life. Possible The Oral Health Impact Profile - 14 scores range from 0 to 56, with higher score representing poor quality of life.
Measured: Before and on the 7th day after the 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 2025
- Study start1 Dec 2024
- Primary completion15 Dec 2025
- Study completion15 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Impacted Mandibular Third Molar ExtractionStudies 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
- Model description
- The study is a 'split-mouth' randomized clinical controlled trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jelena Krunic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jelena Krunic, University of East Sarajevo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06802354
- Sponsor's protocol ID
- 01-2-9
- Other IDs
- 19.032/961-110/23
- Status last verified
- Jun 2026
- First submitted
- 16 Dec 2024
- Last updated
- 8 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Markovic A, Todorovic Lj. Effectiveness of dexamethasone and low-power laser in minimizing oedema after third molar surgery: a clinical trial. Int J Oral Maxillofac Surg. 2007 Mar;36(3):226-9. doi: 10.1016/j.ijom.2006.10.006. Epub 2006 Dec 8.
PubMed 17157479Carrillo JS, Calatayud J, Manso FJ, Barberia E, Martinez JM, Donado M. A randomized double-blind clinical trial on the effectiveness of helium-neon laser in the prevention of pain, swelling and trismus after removal of impacted third molars. Int Dent J. 1990 Feb;40(1):31-6.
PubMed 2407660Aitken RC. Measurement of feelings using visual analogue scales. Proc R Soc Med. 1969 Oct;62(10):989-93. doi: 10.1177/003591576906201005. No abstract available.
PubMed 4899510Carlsson AM. Assessment of chronic pain. I. Aspects of the reliability and validity of the visual analogue scale. Pain. 1983 May;16(1):87-101. doi: 10.1016/0304-3959(83)90088-X.
PubMed 660296734. Pell GJ, Gregory BT. Impacted mandibular third molars: Classification and Impacted mandibular third molars: Classification and modified technique for removal. Dent. Digest. 1933;39:330-8.
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Application of Gaseous Ozone in the Surgical Extraction of Impacted Mandibular Third Molars: Impact on the Incidence of Postoperative Complications and Healing Processes
- ClinicalTrials.gov ID
- NCT06802354
- Acronym / sponsor ID
- 01-2-9
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Jelena KrunicUniversity, hospital or other
- Study start
- 1 Dec 2024 (actual)
- Primary completion
- 15 Dec 2025 (actual)
- Study completion
- 15 Dec 2025 (actual)
- First posted
- 31 Jan 2025 (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 goal of this clinical trial is to learn if use of ozone works to treat complications after impacted mandibular third molar surgery. It will also learn does ozone has positive effect on wound healing and quality of life.
The main questions it aims to answer are:
- Does ozone reduce incidence of postoperative compliactions such as pain, swelling or reduced mouth opening after impacted mandibular third molar surgery?
- Does ozone improve wound healing after impacted mandibular third molar surgery?
- Does ozone have positive effect on quality of life after impacted mandibular third molar surgery?
Participants will:
- Receive ozone after impacted mandibular third molar surgery.
- Visit the clinic 1st, 3rd, and 7th days after the intervention for checkups and tests.
- Keep a diary of their symptoms.
Detailed description
The aims of this study were: (i) to determine the effects of gaseous ozone on pain, swelling, and trismus and healing process measured by cytokine levels, and (ii) to measure patient quality of life after impacted mandibular third molar surgery.
All participants included in the study will be informed about the aims and expected outcomes of the research, the sample collection procedure, and will sign an informed consent form. All participants will be treated according to the principles of good clinical practice and in accordance with the Helsinki Declaration. The Ethics Committee of the Faculty of Medicine provide study approval.
The surgical procedure for each patient will be performed using a standardized surgical technique in two clinical visits (one side per visit).
The surgical area will be disinfected. To ensure pain relief during the procedure, local anesthesia will be applied using blocks of the inferior alveolar and buccal nerves. After elevating the flap, osteotomy will be performed with a carbide drill using an air drill and continuous irrigation with saline solution. Depending on the morphology of the tooth, the third molar will either be extracted or the crown will be separated from the roots (separation). The wound will be primarily closed with individual sutures, and the sutures will be removed on the seventh postoperative day. After the surgical extraction of the third molar belonging the ozone therapy group, gaseous ozone will be applied to the extraction wound. Ozone will be reapplied 3 days after the intervention. After the surgical extraction of the third molar assigned to the sham ozone therapy, ozone will be applied by placing an inactive AV probe at the extraction site. The sham ozone therapy will also be applied 3 days after the surgical intervention. Postoperative instructions will be given to participants regarding oral hygiene maintenance, the use of cold compresses, and dietary recommendations. All participants will be invited for follow-up examinations on the 1st, 3rd and 7th day after the intervention.
Statistical data analysis will be conducted using SPSS version 20.0 (IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp, USA). Normality testing will be performed, and depending on the results, parametric and/or non-parametric tests will be applied. To compare differences between groups, chi-square tests, independent t-tests, and/or Mann-Whitney tests will be used. To determine differences within groups, paired t-tests and/or Wilcoxon tests will be applied. The correlation between variables will be determined using Pearson or Spearman correlation. A p-value of <0.05 will be considered statistically significant in all analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The study is a 'split-mouth' randomized clinical controlled trial.
| Arm | Type | Receives |
|---|---|---|
| Ozone therapy | Experimental | Drug: OzoneAfter the surgical extraction of the impacted mandibular third molar, gaseous ozone will be applied at the extraction site. Ozone will be reapplied 3 days after the intervention, according to the manufacturer's recommendation for wound treatment following tooth extraction. |
| Sham Comparator | Sham comparator | Drug: PlaceboAfter the surgical extraction of the impacted mandibular third molar, a sham ozone therapy will be applied at the extraction site. The sham ozone therapy will also be reapplied 3 days after the surgical intervention. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients over 18 years
- Patients with bilaterally impacted mandibular third molars classified as impaction index II B
- Patients in good general health (based on the ASA classification as ASA I and ASA II).
Key exclusion criteria (4 listed)
- Contraindications for ozone application (pregnancy, hyperthyroidism, favism, anemia, myasthenia, bleeding disorders, alcohol intoxication, myocardial infarction, pacemaker, allergy to ozone)
- Patients who have used corticosteroid and antibiotic therapy in the last three months prior to inclusion in the study
- Patients with signs of local inflammation in the oral cavity
- Female patients during pregnancy and breastfeeding.
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 |
|---|---|---|
| OzoneIn Ozone group, ozone will be applied at the site of the extraction wound for 30 seconds after the surgical extraction of the third molar, according to the manufacturer's recommendation for wound treatment following tooth extraction. | Drug | Ozone therapy |
| PlaceboIn the control group, a sham ozone therapy will be applied at the site of the extraction wound for 30 seconds after the surgical extraction of the third molar . | Drug | Sham Comparator |
Primary outcome
Postoperative complication: pain
Time frame: 1st, 3rd, and 7th days after the intervention
For the assessment of postoperative pain, the Numeric Visual Analogue Scale (VAS) (Carlsson, 1983) and the Verbal Rating Scale (VRS) (Aitken et al., 1969) will be used, which patients will complete. VAS is a horizontally drawn line of 100 mm in length, where the left end represents the absence of pain (0 mm), and the right end (100 mm) represents the worst pain ever experienced. The pain intensity will be determined by measuring the distance from the marked point on the scale to the left side of the scale and expressed in millimeters. The VRS is a numerical assessment of pain intensity based on six levels: 1 - no pain, 2 - very mild pain, 3 - mild pain, 4 - moderate pain, 5 - severe pain, 6 - very severe pain.
Postoperative complication: trismus
Time frame: 1st, 3rd, and 7th days after the intervention
The degree of postoperative trismus will be assessed by measuring the distance between the mesio-incisal angles of the upper and lower central incisors with the mouth fully open, using a caliper. The value will be expressed in millimeters (Marković and Todorović, 2007).
Postoperative complication: swelling
Time frame: 1st, 3rd, and 7th days after the intervention
The assessment of postoperative swelling will be performed by calculating the postoperative edema coefficient (Ec) using the modified formula by Carrillo et al. (1990): Postoperative distance - Preoperative distance x 100 /Preoperative distance. The postoperative Ec will be obtained by measuring in millimeters the preoperative and postoperative distances between the following reference points (R): AC - the most posterior point on the tragus to the lateral point at the corner of the mouth, AD - the most posterior point on the tragus to the prominent soft tissue landmark and BE - the lateral canthus of the eye to the lowest point on the angle of the mandible. Measurement will be done with a flexible ruler just before the intervention (the baseline value used for evaluating subsequent values).
Cytokine levels- wound healing
Time frame: After surgical intervention, 3rd and 7th days after the intervention
To determine the expression of IL-1β, IL-6, IL-8, TNF-α, VEGF, and TGF-β in samples from extraction wounds, real-time polymerase chain reaction (qPCR) will be used. Gene expression will be determined using "housekeeping" genes as standards and appropriate primers, according to the manufacturer's instructions. Each sample will be analyzed in duplicate.
1 secondary outcome
Measurement of Quality of life of patients using The Oral Health Impact Profile - 14 (OHIP-14) before and 7th day after surgical intervention
Time frame: Before and on the 7th day after the 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 8 Jun 2026.
- Background: PubMed 17157479Markovic A, Todorovic Lj. Effectiveness of dexamethasone and low-power laser in minimizing oedema after third molar surgery: a clinical trial. Int J Oral Maxillofac Surg. 2007 Mar;36(3):226-9. doi: 10.1016/j.ijom.2006.10.006. Epub 2006 Dec 8.
- Background: PubMed 2407660Carrillo JS, Calatayud J, Manso FJ, Barberia E, Martinez JM, Donado M. A randomized double-blind clinical trial on the effectiveness of helium-neon laser in the prevention of pain, swelling and trismus after removal of impacted third molars. Int Dent J. 1990 Feb;40(1):31-6.
- Background: PubMed 4899510Aitken RC. Measurement of feelings using visual analogue scales. Proc R Soc Med. 1969 Oct;62(10):989-93. doi: 10.1177/003591576906201005. No abstract available.
- Background: PubMed 6602967Carlsson AM. Assessment of chronic pain. I. Aspects of the reliability and validity of the visual analogue scale. Pain. 1983 May;16(1):87-101. doi: 10.1016/0304-3959(83)90088-X.
- Background34. Pell GJ, Gregory BT. Impacted mandibular third molars: Classification and Impacted mandibular third molars: Classification and modified technique for removal. Dent. Digest. 1933;39:330-8.
- Individual participant dataSharing planned: Yes
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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.
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 3 study testing Ozone in people with Impacted Mandibular Third Molar Extraction, run by Jelena Krunic at 1 site in Bosnia and Herzegovina.
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 4 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 8 Jun 2026. 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 Bosnia and Herzegovina. 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. Some participants in this study may receive a placebo. 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?
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?
Postoperative complication: pain (time frame: 1st, 3rd, and 7th days after the intervention). The study lists 4 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 NCT06802354, which also lists 5 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 8 Jun 2026.