A Comparison of Recovery After Impacted Wisdom Tooth Removal

NCT07304882 | Completed Phase 3

• 2 other identifiers: 1445/0012/UREC/USTISRCTN15432618
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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 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 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. 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. 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.
3. 3.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.
4. 4.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.
5. 5.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.

Conditions

Impacted Mandibular Third Molar Extraction; Post Operative Complications

Keywords

Serratiopeptidase; Escin; Mandibular third molar surgery; Post operative complications; Trismus; Facial edema; Pain; Triple-blind; RCT; Split-mouth design

Outcome Measures

Primary Outcomes (3)

• 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)

  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.

• 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

  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.

• 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.

  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.

Study Arms (4)

Serratiopeptidase (Test 1)

EXPERIMENTAL

This 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.

Drug: serratiopeptidase

Conventional medication (Control 1)

ACTIVE COMPARATOR

During 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.

Drug: Conventional drugs

Escin (Test 2)

EXPERIMENTAL

This 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

Drug: Escin

Conventional medication (Control 2)

ACTIVE COMPARATOR

During 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.

Drug: Conventional drugs

Interventions

serratiopeptidase DRUG

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

Also known as: Amoxicillin, Metronidazole, and Diclofenac sodium

Serratiopeptidase (Test 1)

Escin DRUG

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

Also known as: Amoxicillin, Metronidazole, and Diclofenac sodium

Escin (Test 2)

Conventional drugs DRUG

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

Also known as: Amoxicillin, Metronidazole, and Diclofenac sodium

Conventional medication (Control 1); Conventional medication (Control 2)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Science and Technology, Yemen: lead

Study Sites (1)

University of Science and Technology

Sanaa, Sana'a, Yemen

Location

Related Publications (13)

• 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.

  PMID: 19168326 BACKGROUND

• 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.

  PMID: 26155332 BACKGROUND

• 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.

  PMID: 24067485 BACKGROUND

• 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.

  PMID: 27837346 BACKGROUND

• 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.

  PMID: 19815952 BACKGROUND

• 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.

  PMID: 30311061 BACKGROUND

• 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.

  PMID: 23304525 BACKGROUND

• 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.

  PMID: 26578119 BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 22916697 BACKGROUND

• 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.

  PMID: 27311846 BACKGROUND

• 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.

  PMID: 27114091 BACKGROUND

• 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.

  PMID: 18272344 BACKGROUND

MeSH Terms

Conditions

Trismus; Pain

Interventions

serratiopeptidase; Amoxicillin; Metronidazole; Diclofenac; Escin

Condition Hierarchy (Ancestors)

Spasm; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Pentacyclic Triterpenes; Triterpenes; Terpenes; Hydrocarbons; Saponins; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 26, 2025
• Study Start: November 30, 2023
• Primary Completion: January 4, 2025
• Study Completion: January 4, 2025
• Last Updated: December 26, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

YE (1)