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Impacted Mandibular Third Molar ExtractionPhase 3CESE-3MNCT07304882

A Comparison of Recovery After Impacted Wisdom Tooth Removal

A Phase 3 study testing serratiopeptidase, Escin and Conventional drugs in people with Impacted Mandibular Third Molar Extraction and Post Operative Complications, run by University of Science and Technology, Yemen at 1 site in Yemen.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Justification of the Study There is a high prevalence of impacted third molars, often accompanied by a range of postoperative complications. To the best of the researcher's knowledge, no clinical study to date has directly compared the efficacy of serratiopeptidase and escin in minimizing the most commonly observed… Read more about this study

Who is it for?
Any age
What is being tested?
serratiopeptidase, Escin and Conventional drugs
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteYemen
Study dates
30 Nov 2023to 4 Jan 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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Medically healthy.
  • Presence of two mandibular third molars indicated for surgical extraction.
  • No history of pericoronitis or other signs of inflammation within the past 30 days.

Who cannot join

  • Current use of other medications such as NSAIDs or corticosteroids.
  • Known allergy to any drugs administered in this study.
  • Pregnancy or breastfeeding.
  • History of diabetes or hypertension.
  • Previous irradiation to the maxillofacial region.
  • Intellectual disability or inability to attend follow-up visits.
  • Presence of acute or subacute pericoronitis.

Trial locations and contacts

1 site in 1 country.

Yemen1 site

  • University of Science and Technology

    Sanaa, Sana'a

Other trials in Yemen

About this study

Official title: Comparison of Efficacy of Serratiopeptidase and Escin After Impacted Mandibular Third Molar Surgery: A Randomized Controlled Clinical Trial

Justification of the Study There is a high prevalence of impacted third molars, often accompanied by a range of postoperative complications. To the best of the researcher's knowledge, no clinical study to date has directly compared the efficacy of serratiopeptidase and escin in minimizing the most commonly observed postoperative complications following impacted mandibular third molar surgery. This study seeks to address this gap by providing empirical evidence that could contribute to optimizing postoperative care.

Objectives of the Study

Read more

Drawing from the background and research questions outlined above, the objectives of this study are divided into general and specific ones, outlined as follows:

General Objective To compare the efficacy of serratiopeptidase and escin, when used as adjuncts to conventional drugs, in reducing postoperative complications (i.e., trismus, facial edema, and pain) following impacted mandibular third molar surgery.

Specific Objectives

The study set the following specific objectives:

  1. To evaluate the efficacy of serratiopeptidase, as an adjunct to conventional drugs, in reducing postoperative complications (i.e., trismus, facial edema, and pain) following impacted mandibular third molar surgery.
  2. To evaluate the efficacy of escin, as an adjunct to conventional drugs, in reducing postoperative complications (i.e., trismus, facial edema, and pain) following impacted mandibular third molar surgery.

Study Hypotheses The study formulated the following hypotheses

  1. Serratiopeptidase, as an adjunct to conventional drugs, provides significantly greater efficacy than conventional drugs alone in reducing postoperative complications (i.e., trismus, facial edema, and pain) following impacted mandibular third molar surgery.
  2. Escin, as an adjunct to conventional drugs, provides significantly greater efficacy than conventional drugs alone in reducing postoperative complications (i.e., trismus, facial edema, and pain) following impacted mandibular third molar surgery.
  3. There is a statistically significant difference in the efficacy of serratiopeptidase compared to escin in reducing postoperative complications (i.e., trismus, facial edema, and pain) when both are used as adjuncts to conventional drugs following impacted mandibular third molar surgery.
Read the detailed description

This clinical trial employed a split-mouth design, wherein two different treatments were randomly assigned to opposite halves of each patient's mouth. The study was conducted as a triple-blind randomized trial to minimize bias and enhance scientific rigor. The procedures were carried out by the researcher; however, the operator was blinded to the evaluation data. The evaluator, who had access to patients' symptom responses, remained unaware of which treatment was administered on each side. Likewise, patients were blinded to the treatment or intervention applied to each side of their mouth.

Participants were allocated into two groups, with each patient serving as their own control through the split-mouth approach. On one side, an impacted mandibular third molar was extracted and treated with conventional medications. After a washout period of three weeks, the contralateral molar was extracted and treated with an additional intervention alongside the conventional drugs-either an enzyme or a herbal agent. The groups were defined as follows:

  • The first group received conventional medications combined with 10 mg oral serratiopeptidase, administered immediately postoperatively and then thrice daily for five days following the first surgical visit. During the second visit (after three weeks), only conventional drugs were given, or vice versa.
  • The second group received conventional medications combined with 20 mg oral escin, administered immediately postoperatively and then thrice daily for five days following the first surgical visit. At the second visit (after three weeks), only conventional drugs were administered, or vice versa.

The conventional medication administered to both groups consisted of Amoxicillin 500 mg capsules twice daily, Metronidazole 500 mg tablets three times daily, and Diclofenac sodium 50 mg tablets twice daily.

Being tested
serratiopeptidase, Escin, Conventional drugs
Keywords
Serratiopeptidase, Escin, Mandibular third molar surgery, Post operative complications, Trismus, Facial edema, Pain, Triple-blind, RCT, Split-mouth design
Medical subject headings
Trismus, Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • serratiopeptidaseDrug

    Also called Amoxicillin, Metronidazole, and Diclofenac sodium

    10 mg oral serratiopeptidase , Amoxicillin 500 mg, Metronidazole 500 mg, Diclofenac sodium 50 mg

  • EscinDrug

    Also called Amoxicillin, Metronidazole, and Diclofenac sodium

    20 mg oral escin , Amoxicillin 500 mg, Metronidazole 500 mg, Diclofenac sodium 50 mg

  • Conventional drugsDrug

    Also called Amoxicillin, Metronidazole, and Diclofenac sodium

    Amoxicillin 500 mg, Metronidazole 500 mg, Diclofenac sodium 50 mg

Study groups in NCT07304882
Study groupRoleWhat they receive
Serratiopeptidase (Test 1)ExperimentalThis group received conventional medications combined with 10 mg oral serratiopeptidase, administered immediately postoperatively and then thrice daily for five days following the first surgical visit.
Receives: Drug: serratiopeptidase
Conventional medication (Control 1)Active comparatorDuring the second visit (after three weeks), only conventional drugs were given. It was consisted of Amoxicillin 500 mg capsules twice daily, Metronidazole 500 mg tablets three times daily, and Diclofenac sodium 50 mg tablets twice daily.
Receives: Drug: Conventional drugs
Escin (Test 2)ExperimentalThis group received conventional medications combined with 20 mg oral escin, administered immediately postoperatively and then thrice daily for five days following the first surgical visit
Receives: Drug: Escin
Conventional medication (Control 2)Active comparatorDuring the second visit (after three weeks), only conventional drugs were given. It was consisted of Amoxicillin 500 mg capsules twice daily, Metronidazole 500 mg tablets three times daily, and Diclofenac sodium 50 mg tablets twice daily.
Receives: Drug: Conventional drugs

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Facial Edema

    Facial edema was assessed using the method described by Schultze-Mosgau et al. (1995) to quantitatively evaluate edema both before and after surgery. Measurements were taken with a flexible measuring scale while the patient maintained a closed-mouth position. Five fixed anatomical landmarks and three baseline reference lines were used for consistency:

    • Fixed points: F1 - Tragus of the ear F2 - Angle of the mandible F3 - Soft tissue pogonion F4 - Corner of the mouth F5 - Lateral canthus of the eye
    • Baseline reference lines: S1 - From tragus of the ear to corner of the mouth (Tr-Com) S2 - From tragus of the ear to soft tissue pogonion (Tr-Pgo) S3 - From lateral canthus of the eye to angle of the mandible (Lc-Gn)

    Measured: Baseline measurements were recorded preoperatively. Measurements were reassessed at specific post-operative intervals: immediately after surgery and on the 2nd, 3rd, and 5th postoperative days.

  2. Trismus

    Trismus was evaluated by measuring the change in maximum mouth opening before and after the surgical procedure. Using a calibrated ruler, the distance between the incisal edges of the upper and lower central incisors was measured in millimeters

    Measured: Baseline measurements were recorded preoperatively. Measurements were reassessed at specific post-operative intervals: immediately after surgery and on the 2nd, 3rd, and 5th postoperative days.

  3. Pain Intensity

    Pain intensity was evaluated both pre-operatively and post-operatively using a standardized 10-centimeter visual analogue scale (VAS), as described by Sirintawat et al. (2017). The scale ranged from 0, representing no pain, to 10, indicating the worst imaginable pain. At each assessment interval, patients reported the degree of pain they experienced on the scale, providing a simple yet reliable measure of subjective pain.

    Measured: Baseline measurements were recorded preoperatively. Measurements were reassessed at specific post-operative intervals: immediately after surgery and on the 2nd, 3rd, and 5th postoperative days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Dec 2025
  2. Study start30 Nov 2023
  3. Primary completion4 Jan 2025
  4. Study completion4 Jan 2025

Resources

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
Crossover
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07304882
Sponsor's protocol ID
1445/0012/UREC/UST
Other IDs
ISRCTN15432618
Acronym
CESE-3M
Status last verified
Oct 2025
First submitted
21 Nov 2025
Last updated
26 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chopra D, Rehan HS, Mehra P, Kakkar AK. A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model. Int J Oral Maxillofac Surg. 2009 Apr;38(4):350-5. doi: 10.1016/j.ijom.2008.12.013. Epub 2009 Jan 24.

    PubMed 19168326

  • Chappi D M, Suresh KV, Patil MR, Desai R, Tauro DP, Bharani K N S S, Parkar MI, Babaji HV. Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae after lower third molar surgery. J Clin Exp Dent. 2015 Apr 1;7(2):e197-202. doi: 10.4317/jced.51868. eCollection 2015 Apr.

    PubMed 26155332

  • Sannino G, Gigola P, Puttini M, Pera F, Passariello C. Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis. Int J Immunopathol Pharmacol. 2013 Jul-Sep;26(3):825-31. doi: 10.1177/039463201302600332.

    PubMed 24067485

  • Bataineh AB, Batarseh RA. The effect of modified surgical flap design for removal of lower third molars on lingual nerve injury. Clin Oral Investig. 2017 Jul;21(6):2091-2099. doi: 10.1007/s00784-016-1999-5. Epub 2016 Nov 12.

    PubMed 27837346

  • Wang T, Fu F, Zhang L, Han B, Zhu M, Zhang X. Effects of escin on acute inflammation and the immune system in mice. Pharmacol Rep. 2009 Jul-Aug;61(4):697-704. doi: 10.1016/s1734-1140(09)70122-7.

    PubMed 19815952

  • Isola G, Matarese M, Ramaglia L, Iorio-Siciliano V, Cordasco G, Matarese G. Efficacy of a drug composed of herbal extracts on postoperative discomfort after surgical removal of impacted mandibular third molar: a randomized, triple-blind, controlled clinical trial. Clin Oral Investig. 2019 May;23(5):2443-2453. doi: 10.1007/s00784-018-2690-9. Epub 2018 Oct 11.

    PubMed 30311061

  • Pavan R, Jain S, Shraddha, Kumar A. Properties and therapeutic application of bromelain: a review. Biotechnol Res Int. 2012;2012:976203. doi: 10.1155/2012/976203. Epub 2012 Dec 10.

    PubMed 23304525

  • Olmedo-Gaya MV, Manzano-Moreno FJ, Galvez-Mateos R, Gonzalez-Rodriguez MP, Talero-Sevilla C, Vallecillo-Capilla M. Oral pregabalin for postoperative pain relief after third molar extraction: a randomized controlled clinical trial. Clin Oral Investig. 2016 Sep;20(7):1819-26. doi: 10.1007/s00784-015-1657-3. Epub 2015 Nov 18.

    PubMed 26578119

  • Villafuerte-Nuñez AE, Téllez-Anguiano AC, Hernández-Díaz O, Rodríguez-Vera R, Gutiérrez-Gnecchi JA, Salazar-Martínez JL. Facial edema evaluation using digital image processing. Discrete Dynamics in Nature and Society. 2013;2013(1):927843. https://doi.org/10.1155/2013/927843

  • Piecuch JF. What strategies are helpful in the operative management of third molars? J Oral Maxillofac Surg. 2012 Sep;70(9 Suppl 1):S25-32. doi: 10.1016/j.joms.2012.04.027.

    PubMed 22916697

  • Kaplan V, Eroglu CN. Comparison of the Effects of Daily Single-Dose Use of Flurbiprofen, Diclofenac Sodium, and Tenoxicam on Postoperative Pain, Swelling, and Trismus: A Randomized Double-Blind Study. J Oral Maxillofac Surg. 2016 Oct;74(10):1946.e1-6. doi: 10.1016/j.joms.2016.05.015. Epub 2016 May 24.

    PubMed 27311846

  • Brkovic B, Andric M, Calasan D, Milic M, Stepic J, Vucetic M, Brajkovic D, Todorovic L. Efficacy and safety of 1% ropivacaine for postoperative analgesia after lower third molar surgery: a prospective, randomized, double-blinded clinical study. Clin Oral Investig. 2017 Apr;21(3):779-785. doi: 10.1007/s00784-016-1831-2. Epub 2016 Apr 25.

    PubMed 27114091

  • Al-Khateeb TH, Nusair Y. Effect of the proteolytic enzyme serrapeptase on swelling, pain and trismus after surgical extraction of mandibular third molars. Int J Oral Maxillofac Surg. 2008 Mar;37(3):264-8. doi: 10.1016/j.ijom.2007.11.011. Epub 2008 Feb 12.

    PubMed 18272344

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing serratiopeptidase, Escin and Conventional drugs in people with Impacted Mandibular Third Molar Extraction and Post Operative Complications, run by University of Science and Technology, Yemen at 1 site in Yemen.

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 7 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 26 Dec 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 Yemen. 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?

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?

Facial Edema (time frame: Baseline measurements were recorded preoperatively. Measurements were reassessed at specific post-operative intervals: immediately after surgery and on the 2nd, 3rd, and 5th postoperative days.). 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 NCT07304882, which also lists 13 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 26 Dec 2025.

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