The Effect of Three Different Medications on Anesthetic Success and Postoperative Pain

The Effect of Premedication With Trypsin, Bromelain and Rutoside Combination on the Success of IAN Block and Post Endodontic Pain in Patients With Symptomatic Irreversible Pulpitis: A Randomized Clinical Trial

Pain is a very important factor in Endodontic treatment, Both intra- and Post-operatively. In case of symptomatic Irreversible pulpitis, a build up of inflammatory mediators makes it very difficult for the operator to reach the desired level of anesthesia in order to deliver a pain free treatment as well as to eliminate or at least reduce post-operative pain incidence and severity. therefore, a number of pre- medications was suggested with variable success rates. Therefore this trial aims at the use of a new category of anti-inflammatory medications which would be less harmful than the standard NSAIDs or steroids.

Study Overview

• Status: Completed
• Conditions: Symptomatic Irreversible Pulpitis
• Intervention / Treatment: Drug: Trypsin, Bromelain and Rutoside; Drug: Diclofenac Potassium 50mg Tab; Drug: Prednisolone Oral Tablet; Other: Placebo

Detailed Description

Background and Rationale

For patients with irreversible pulpitis, achieving adequate pulpal anesthesia during endodontic therapy is a major concern, posing a considerable difficulty from a clinical point of view as an inadequately anesthetized hot tooth with severe pain will not only elevate the patients' apprehension but will also stress the practicing clinician. Inferior alveolar nerve block (IANB) technique is commonly used to achieve pulpal anesthesia in mandibular teeth. The failure rates of a single IANB block injection of local anesthetic in patients with irreversible pulpitis range between 30 and 90 %.

Several clinical studies identified inflammation as a major cause of failure of local anesthesia and an important component of the pathogenesis of hyperalgesia. The use of both steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs) was investigated to improve the success rates of IANB anesthesia. Combined with the bioflavonoid rutin (Rutoside), the proteases Trypsin and Bromelain have been extensively investigated as alternatives to conventional therapies for pain and swelling associated with diverse conditions.

The aim of the trial To assess the effect of Trypsin, Bromelain and Rutoside combination versus ibuprofen or dexamethasone or placebo on the anesthetic success of IANB and postoperative pain in patients with symptomatic irreversible pulpitis.

The null hypothesis tested is " In patients with symptomatic irreversible pulpitis in their mandibular molars, there is no difference between Trypsin, Bromelain and Rutoside combination or ibuprofen or dexamethasone or placebo on anesthetic success and post-operative pain after endodontic treatment."

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 4450113
    • Faculty of Dentistry, Cairo University
  • Cairo Governorate
    • Cairo, Cairo Governorate, Egypt, 11829
      • Faculty of Oral and Dental Medicine, Egyptian Russian University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with symptomatic irreversible pulpitis.
• Patients with active pain (moderate-to-severe) in mandibular molars.
• Males and females.
• Patient with the ability to understand and use pain scales.
• Patient who accepts to enroll to the study

Exclusion Criteria:

• Patients' allergies or any other contraindication to any of the used medications or mepivacaine.
• Pregnant and lactating females.
• Patients have been taking pain medication 12 hours earlier.
• Patient has more than one symptomatic mandibular tooth in the same quadrant.
• Patients with periradicular pathosis and/or radiolucency other than widened periodontal ligaments.
• Patients with contributory medical history (ASA>II).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trypsin, Bromelain and Rutoside (TBR) Group; patients will receive Trypsin, Bromelain and Rutoside combination (2 tablets of flamogen a combination of Trypsin 48mg, Bromelain 90mg and Rutoside 100mg) as a single oral dose 1 hour before treatment.	Drug: Trypsin, Bromelain and Rutoside; Flamogen is a combination of trypsin 48 mgs, bromelain 90mg and rutoside 100 mg in one tablet that provides an anti inflammatory, anti edematous activity. each patient will receive a single dose of 2 tablets one hour before treatment.; Other Names: Flamogen
Active Comparator: NSAIDs Group; Patients will receive Diclofenac Potassium (50 mg) as a single oral dose 1 hour before treatment.	Drug: Diclofenac Potassium 50mg Tab; Non-steroidal anti inflammatory drug. Cataflam is known for its potent anti inflammatory and analgesic properties. each patient will receive one tablet of Cataflam 50 mg 1 hour before treatment.
Active Comparator: Steroid Group; Patients will receive a single oral dose of a steroid drug (20 mg prednisolone) 1 hour before treatment.	Drug: Prednisolone Oral Tablet; Steroids are potent anti inflammatory drugs, patients are going to receive one tablet of 20 mg solupred one hour before treatment; Other Names: solupred
Placebo Comparator: Placebo group; Patients will receive a single oral dose of placebo (opaque white capsule filled with starch) 1 hour before treatment	Other: Placebo; An opaque white capsule filled with starch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success of Anesthesia	Success of Inferior alveolar Nerve block anesthesia will be measured by recording the patient's pain severity before and after anesthesia administration as well as during endodontic procedures. each patient will record his/her pain on a "Numerical Rating Scale" (NRS), the NRS is an eleven point scale anchored at both ends by zero representing no pain and 10 representing pain as bad as it could be.	Perioperative
Post-operative pain	postoperative pain as recorded by the patient after completion of treatment in on visit. patient will receive a pain diary to record their postoperative pain incidence and severity at 6, 12, 24, 72 hours and 7 days after endodontic treatment. Each patient will record his/her pain on a "Numerical Rating Scale" (NRS), the NRS is an eleven point scale anchored at both ends by zero representing no pain and 10 representing pain as bad as it could be.	Each patient will deliver his/her pain diary one week after root canal treatment

Collaborators and Investigators

• Sponsor: Cairo University
• Collaborators: Egyptian Russian University
• Investigators: Principal Investigator: Maha Nasr, Egyptian Russian University

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2025
• Primary Completion (Actual): February 15, 2026
• Study Completion (Actual): March 15, 2026

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: March 5, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Dental Pulp Diseases; Tooth Diseases; Pulpitis; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Carboxylic Acids; Polycyclic Compounds; Hydrolases; Enzymes; Enzymes and Coenzymes; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Acids, Carbocyclic; Benzopyrans; Endopeptidases; Peptide Hydrolases; Flavonols; Flavonoids; Chromones; Phenylacetates; Serine Endopeptidases; Serine Proteases; Cysteine Endopeptidases; Cysteine Proteases; Prednisolone; Diclofenac; Rutin; Bromelains; Trypsin
• Other Study ID Numbers: ERU1

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