Wisdom Tooth RemovalPhase 4NCT07844824
Effect of Subperiosteal Ropivacaine After Third Molar Extraction
A Phase 4 study testing Ropivacaine 0.75% and Saline (0.9% NaCl) in people with Wisdom Tooth Removal and Dental Anesthesia, run by University of Zagreb at 1 site in Croatia.
Trial summary
This study examined whether an additional injection of the long-acting local anesthetic ropivacaine at the surgical site could reduce pain and improve recovery after removal of lower wisdom teeth. Adults aged 18 to 65 years who needed both lower wisdom teeth removed could take part. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Wisdom Tooth Removal, Dental Anesthesia, Ropivacaine
- What is being tested?
- Ropivacaine 0.75% and Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteCroatia
- Study dates
- 2 Oct 2023to 26 Aug 2024
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 to 65 years.
- American Society of Anesthesiologists (ASA) physical status I.
- Presence of both mandibular third molars, with both teeth indicated for surgical extraction.
- Both mandibular third molars of the same Pell and Gregory classification.
- Satisfactory dental and oral health, without acute inflammatory processes at the surgical site or elsewhere in the oral cavity, including pericoronitis, pulpitis, or apical periodontitis.
- No use of analgesic medication within 24 hours before surgery.
Show all 9Show fewer
- No use of antibiotics within 1 month before surgery.
- Ability and willingness to provide written informed consent.
- Willingness and ability to comply with study procedures and follow-up.
Who cannot join
- American Society of Anesthesiologists (ASA) physical status II, III, or IV.
- Pregnancy or breastfeeding.
- Known allergy to amide-type local anesthetics, vasoconstrictors, or related compounds.
- Use of dietary supplements that could affect local anesthesia.
- History of drug or analgesic abuse.
- Unsatisfactory dental or oral health, including untreated dental caries, periodontitis, or periapical lesions.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Supplementary Subperiosteal 0.75% Ropivacaine on Postoperative Outcomes After Mandibular Third Molar Extraction: a Randomized, Split-mouth Trial
This study examined whether an additional injection of the long-acting local anesthetic ropivacaine at the surgical site could reduce pain and improve recovery after removal of lower wisdom teeth. Adults aged 18 to 65 years who needed both lower wisdom teeth removed could take part. Each participant underwent two separate wisdom tooth removal procedures, approximately two weeks apart. After one procedure, ropivacaine was injected near the surgical area, while after the other procedure, a sterile saline solution was given in the same way for comparison. Neither the participant nor the surgeon knew which treatment was used at each procedure. Participants recorded their pain after surgery and their use of pain-relieving medication. Mouth opening and the effect of the procedure on daily life and oral health-related quality of life were also assessed. The purpose of the study was to determine whether adding ropivacaine at the surgical site could provide better pain relief and postoperative recovery than standard treatment alone.
Read the detailed description
This was a single-center, randomized, double-blind, placebo-controlled, split-mouth clinical trial conducted in patients requiring surgical removal of both mandibular third molars.
Each participant underwent two separate surgical procedures two weeks apart. For each participant, one mandibular third molar surgical site was randomly assigned to receive supplementary 0.75% ropivacaine and the contralateral surgical site received 0.9% sterile saline as placebo. Treatment allocation to the right or left side was determined using a computer-generated randomization sequence. Sequentially numbered, sealed, opaque envelopes were used for allocation concealment. The study solutions were prepared in identical syringes. Both the participant and the surgeon were blinded to treatment allocation.
All surgical procedures were performed by the same oral surgery specialist using a standardized surgical technique. Standard local anesthesia consisted of an inferior alveolar nerve block and long buccal nerve block with articaine hydrochloride and adrenaline. Following extraction and suturing, 2 mL of either 0.75% ropivacaine or 0.9% sterile saline was administered subperiosteally at the buccal aspect of the surgical site, slightly apical to the extraction socket. At the second surgical appointment, the contralateral side received the alternate study treatment.
Postoperative management was standardized for both procedures. Participants received instructions regarding local cooling, oral hygiene, and use of chlorhexidine mouth rinse. Ibuprofen 400 mg was permitted as rescue analgesic medication when required.
Participants were followed for 7 days after each surgical procedure. The study was designed to assess whether supplementary subperiosteal ropivacaine administered after mandibular third molar surgery could improve postoperative recovery compared with placebo while allowing each participant to serve as their own control.
- Conditions
- Wisdom Tooth Removal, Dental Anesthesia, Ropivacaine
- Being tested
- Ropivacaine 0.75%, Saline (0.9% NaCl)
- Keywords
- Ropivacaine, Dental anaesthesia, Third molar removal, Third molar extraction, Supplementary anesthesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ropivacaine 0.75%Drug
Following surgical extraction and suturing of the mandibular third molar, 2 mL of 0.75% ropivacaine was administered as a supplementary subperiosteal injection at the buccal aspect of the extraction site, slightly apical to the bony socket.
Saline (0.9% NaCl)Other
Following surgical extraction and suturing of the mandibular third molar, 2 mL of 0.9% sterile saline was administered as a supplementary subperiosteal injection at the buccal aspect of the extraction site, slightly apical to the bony socket.
| Study group | Role | What they receive |
|---|---|---|
| Ropivacaine-treated site | Experimental | Following surgical extraction and suturing of the mandibular third molar, the assigned surgical site received a supplementary subperiosteal injection of 2 mL of 0.75% ropivacaine at the buccal aspect of the extraction site. Receives: Drug: Ropivacaine 0.75% |
| Placebo-treated site | Placebo comparator | Following surgical extraction and suturing of the mandibular third molar, the assigned surgical site received a supplementary subperiosteal injection of 2 mL of 0.9% sterile saline at the buccal aspect of the extraction site. Receives: Other: Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative Pain Intensity as Assessed by the Visual Analogue Scale (VAS) During the First 72 Hours After Surgery
Participants recorded postoperative pain intensity using a Visual Analogue Scale (VAS) following each mandibular third molar extraction. Pain intensity was recorded separately after the ropivacaine-treated and placebo-treated procedures.
Measured: 2, 4, 6, 12, 24, 48, and 72 hours after surgery
Secondary outcomes (4)
Postoperative Maximal Interincisal Opening as Assessed Using the TheraBite Range of Motion Scale
Participants measured maximal interincisal opening (MIO) in millimeters by placing the TheraBite Range of Motion Scale between the upper and lower central incisors and opening the mouth as wide as possible. Measurements were recorded following each surgical procedure.
Measured: Postoperative days 1, 2, and 3
Time to First Postoperative Rescue Analgesic Intake
Participants recorded the time from completion of surgery to the first intake of rescue analgesic medication (ibuprofen 400 mg). Time to first analgesic intake was recorded following each surgical procedure.
Measured: From completion of surgery until first rescue analgesic intake, assessed up to 72 hours after surgery.
Postoperative Rescue Analgesic Consumption
Participants recorded their consumption of rescue analgesic medication (ibuprofen 400 mg) following each surgical procedure.
Measured: Day of surgery and postoperative days 1, 2, and 3
Oral Health-Related Quality of Life as Assessed by the Oral Health Impact Profile-14 (OHIP-14)
Participants completed the Croatian version of the 14-item Oral Health Impact Profile (OHIP-14) following each surgical procedure. The OHIP-14 total score was used to assess the impact of the surgical procedure on oral health-related quality of life, with higher scores indicating poorer oral health-related quality of life.
Measured: Postoperative day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2026
- Study start2 Oct 2023
- Primary completion26 Aug 2024
- Study completion26 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Wisdom Tooth RemovalStudies 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Each participant underwent two mandibular third molar extraction procedures approximately two weeks apart and received both study interventions. One surgical site was randomly assigned to receive supplementary subperiosteal 0.75% ropivacaine, while the contralateral site received 0.9% sterile saline. The side receiving ropivacaine at the first procedure was randomized, and the alternate intervention was administered at the second procedure. As such, each participant served as their own control.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zagreb
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Igor Shapeski, University of Zagreb
- Investigators
- Davor Brajdic, DMD, PhD, Study chair, School of Dental Medicine Zagreb, University of Zagreb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07844824
- Sponsor's protocol ID
- 05-PA-30-XXIX-9/2021
- Status last verified
- Sep 2026
- First submitted
- 17 Sep 2026
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Steverink JG, Oostinga D, van Tol FR, van Rijen MHP, Mackaaij C, Verlinde-Schellekens SAMW, Oosterman BJ, Van Wijck AJM, Roeling TAP, Verlaan JJ. Sensory Innervation of Human Bone: An Immunohistochemical Study to Further Understand Bone Pain. J Pain. 2021 Nov;22(11):1385-1395. doi: 10.1016/j.jpain.2021.04.006. Epub 2021 May 5.
PubMed 33964414Feldman HS, Covino BG. Comparative motor-blocking effects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog. Anesth Analg. 1988 Nov;67(11):1047-52.
PubMed 3189893Amorim KS, Gercina AC, Ramiro FMS, Medeiros LA, de Araujo JSM, Groppo FC, Souza LMA. Can local anesthesia with ropivacaine provide postoperative analgesia in extraction of impacted mandibular third molars? A randomized clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021 May;131(5):512-518. doi: 10.1016/j.oooo.2020.09.010. Epub 2020 Sep 30.
PubMed 33223455Wang Y, Zhou A. A new improvement: subperiosteal cocktail application to effectively reduce pain and blood loss after total knee arthroplasty. J Orthop Surg Res. 2020 Jan 30;15(1):33. doi: 10.1186/s13018-020-1563-5.
PubMed 32000816
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Supplementary Subperiosteal 0.75% Ropivacaine on Postoperative Outcomes After Mandibular Third Molar Extraction: a Randomized, Split-mouth Trial
- ClinicalTrials.gov ID
- NCT07844824
- Acronym / sponsor ID
- 05-PA-30-XXIX-9/2021
- Conditions
- Wisdom Tooth Removal, Dental Anesthesia, Ropivacaine
- Keywords
- Ropivacaine, Dental anaesthesia, Third molar removal, Third molar extraction, Supplementary anesthesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of ZagrebUniversity, hospital or other
- Study start
- 2 Oct 2023 (actual)
- Primary completion
- 26 Aug 2024 (actual)
- Study completion
- 26 Aug 2024 (actual)
- First posted
- 28 Sep 2026 (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.
This study examined whether an additional injection of the long-acting local anesthetic ropivacaine at the surgical site could reduce pain and improve recovery after removal of lower wisdom teeth. Adults aged 18 to 65 years who needed both lower wisdom teeth removed could take part. Each participant underwent two separate wisdom tooth removal procedures, approximately two weeks apart. After one procedure, ropivacaine was injected near the surgical area, while after the other procedure, a sterile saline solution was given in the same way for comparison. Neither the participant nor the surgeon knew which treatment was used at each procedure. Participants recorded their pain after surgery and their use of pain-relieving medication. Mouth opening and the effect of the procedure on daily life and oral health-related quality of life were also assessed. The purpose of the study was to determine whether adding ropivacaine at the surgical site could provide better pain relief and postoperative recovery than standard treatment alone.
Detailed description
This was a single-center, randomized, double-blind, placebo-controlled, split-mouth clinical trial conducted in patients requiring surgical removal of both mandibular third molars.
Each participant underwent two separate surgical procedures two weeks apart. For each participant, one mandibular third molar surgical site was randomly assigned to receive supplementary 0.75% ropivacaine and the contralateral surgical site received 0.9% sterile saline as placebo. Treatment allocation to the right or left side was determined using a computer-generated randomization sequence. Sequentially numbered, sealed, opaque envelopes were used for allocation concealment. The study solutions were prepared in identical syringes. Both the participant and the surgeon were blinded to treatment allocation.
All surgical procedures were performed by the same oral surgery specialist using a standardized surgical technique. Standard local anesthesia consisted of an inferior alveolar nerve block and long buccal nerve block with articaine hydrochloride and adrenaline. Following extraction and suturing, 2 mL of either 0.75% ropivacaine or 0.9% sterile saline was administered subperiosteally at the buccal aspect of the surgical site, slightly apical to the extraction socket. At the second surgical appointment, the contralateral side received the alternate study treatment.
Postoperative management was standardized for both procedures. Participants received instructions regarding local cooling, oral hygiene, and use of chlorhexidine mouth rinse. Ibuprofen 400 mg was permitted as rescue analgesic medication when required.
Participants were followed for 7 days after each surgical procedure. The study was designed to assess whether supplementary subperiosteal ropivacaine administered after mandibular third molar surgery could improve postoperative recovery compared with placebo while allowing each participant to serve as their own control.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Each participant underwent two mandibular third molar extraction procedures approximately two weeks apart and received both study interventions. One surgical site was randomly assigned to receive supplementary subperiosteal 0.75% ropivacaine, while the contralateral site received 0.9% sterile saline. The side receiving ropivacaine at the first procedure was randomized, and the alternate intervention was administered at the second procedure. As such, each participant served as their own control.
| Arm | Type | Receives |
|---|---|---|
| Ropivacaine-treated site | Experimental | Drug: Ropivacaine 0.75%Following surgical extraction and suturing of the mandibular third molar, the assigned surgical site received a supplementary subperiosteal injection of 2 mL of 0.75% ropivacaine at the buccal aspect of the extraction site. |
| Placebo-treated site | Placebo comparator | Other: Saline (0.9% NaCl)Following surgical extraction and suturing of the mandibular third molar, the assigned surgical site received a supplementary subperiosteal injection of 2 mL of 0.9% sterile saline at the buccal aspect of the extraction site. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18 to 65 years.
- American Society of Anesthesiologists (ASA) physical status I.
- Presence of both mandibular third molars, with both teeth indicated for surgical extraction.
- Both mandibular third molars of the same Pell and Gregory classification.
- Satisfactory dental and oral health, without acute inflammatory processes at the surgical site or elsewhere in the oral cavity, including pericoronitis, pulpitis, or apical periodontitis.
Key exclusion criteria (6 listed)
- American Society of Anesthesiologists (ASA) physical status II, III, or IV.
- Pregnancy or breastfeeding.
- Known allergy to amide-type local anesthetics, vasoconstrictors, or related compounds.
- Use of dietary supplements that could affect local anesthesia.
- History of drug or analgesic abuse.
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 |
|---|---|---|
| Ropivacaine 0.75%Following surgical extraction and suturing of the mandibular third molar, 2 mL of 0.75% ropivacaine was administered as a supplementary subperiosteal injection at the buccal aspect of the extraction site, slightly apical to the bony socket. | Drug | Ropivacaine-treated site |
| Saline (0.9% NaCl)Following surgical extraction and suturing of the mandibular third molar, 2 mL of 0.9% sterile saline was administered as a supplementary subperiosteal injection at the buccal aspect of the extraction site, slightly apical to the bony socket. | Other | Placebo-treated site |
Primary outcome
Postoperative Pain Intensity as Assessed by the Visual Analogue Scale (VAS) During the First 72 Hours After Surgery
Time frame: 2, 4, 6, 12, 24, 48, and 72 hours after surgery
Participants recorded postoperative pain intensity using a Visual Analogue Scale (VAS) following each mandibular third molar extraction. Pain intensity was recorded separately after the ropivacaine-treated and placebo-treated procedures.
4 secondary outcomes
Postoperative Maximal Interincisal Opening as Assessed Using the TheraBite Range of Motion Scale
Time frame: Postoperative days 1, 2, and 3
Time to First Postoperative Rescue Analgesic Intake
Time frame: From completion of surgery until first rescue analgesic intake, assessed up to 72 hours after surgery.
Postoperative Rescue Analgesic Consumption
Time frame: Day of surgery and postoperative days 1, 2, and 3
Oral Health-Related Quality of Life as Assessed by the Oral Health Impact Profile-14 (OHIP-14)
Time frame: Postoperative day 7
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 28 Sep 2026.
- Background: PubMed 33964414Steverink JG, Oostinga D, van Tol FR, van Rijen MHP, Mackaaij C, Verlinde-Schellekens SAMW, Oosterman BJ, Van Wijck AJM, Roeling TAP, Verlaan JJ. Sensory Innervation of Human Bone: An Immunohistochemical Study to Further Understand Bone Pain. J Pain. 2021 Nov;22(11):1385-1395. doi: 10.1016/j.jpain.2021.04.006. Epub 2021 May 5.
- Background: PubMed 3189893Feldman HS, Covino BG. Comparative motor-blocking effects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog. Anesth Analg. 1988 Nov;67(11):1047-52.
- Background: PubMed 33223455Amorim KS, Gercina AC, Ramiro FMS, Medeiros LA, de Araujo JSM, Groppo FC, Souza LMA. Can local anesthesia with ropivacaine provide postoperative analgesia in extraction of impacted mandibular third molars? A randomized clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021 May;131(5):512-518. doi: 10.1016/j.oooo.2020.09.010. Epub 2020 Sep 30.
- Background: PubMed 32000816Wang Y, Zhou A. A new improvement: subperiosteal cocktail application to effectively reduce pain and blood loss after total knee arthroplasty. J Orthop Surg Res. 2020 Jan 30;15(1):33. doi: 10.1186/s13018-020-1563-5.
- 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.
Davor Brajdic, DMD, PhD study chair
School of Dental Medicine Zagreb, University of Zagreb
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 Ropivacaine 0.75% and Saline (0.9% NaCl) in people with Wisdom Tooth Removal and Dental Anesthesia, run by University of Zagreb at 1 site in Croatia.
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 9 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 28 Sep 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 Croatia. 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 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?
Postoperative Pain Intensity as Assessed by the Visual Analogue Scale (VAS) During the First 72 Hours After Surgery (time frame: 2, 4, 6, 12, 24, 48, and 72 hours after surgery). 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 NCT07844824, 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 28 Sep 2026.