A Comparison of Recovery After Impacted Wisdom Tooth Removal (CESE-3M)

December 12, 2025 updated by: Arwa Mohammed Dahak, University of Science and Technology, Yemen

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Yemen
    • Sana'a
      • Sanaa, Sana'a, Yemen
        • University of Science and Technology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Serratiopeptidase (Test 1)
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
10 mg oral serratiopeptidase , Amoxicillin 500 mg, Metronidazole 500 mg, Diclofenac sodium 50 mg
Other Names:
  • Amoxicillin, Metronidazole, and Diclofenac sodium
Active Comparator: Conventional medication (Control 1)
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
Amoxicillin 500 mg, Metronidazole 500 mg, Diclofenac sodium 50 mg
Other Names:
  • Amoxicillin, Metronidazole, and Diclofenac sodium
Experimental: Escin (Test 2)
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
20 mg oral escin , Amoxicillin 500 mg, Metronidazole 500 mg, Diclofenac sodium 50 mg
Other Names:
  • Amoxicillin, Metronidazole, and Diclofenac sodium
Active Comparator: Conventional medication (Control 2)
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
Amoxicillin 500 mg, Metronidazole 500 mg, Diclofenac sodium 50 mg
Other Names:
  • Amoxicillin, Metronidazole, and Diclofenac sodium

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.

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
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.
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
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Science and Technology, Yemen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 30, 2023

Primary Completion (Actual)

January 4, 2025

Study Completion (Actual)

January 4, 2025

Study Registration Dates

First Submitted

November 21, 2025

First Submitted That Met QC Criteria

December 12, 2025

First Posted (Actual)

December 26, 2025

Study Record Updates

Last Update Posted (Actual)

December 26, 2025

Last Update Submitted That Met QC Criteria

December 12, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1445/0012/UREC/UST
  • ISRCTN15432618 (Registry Identifier: ISRCTN - The UK's Clinical Study Registry)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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