Cryotherapy and Intracanal Medicaments for Postoperative Pain in Apical Periodontitis

NCT07437612 | Completed

• 1 other identifier: BSL5R6DP90
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, participant- and outcome assessor-blinded, 2 × 2 factorial clinical trial evaluated the effects of intracanal cryotherapy and two intracanal medicaments-calcium hydroxide and metformin-on postoperative spontaneous and percussion pain in mandibular premolars with pulpal necrosis and symptomatic apical periodontitis. Eighty participants were randomly assigned to four groups: calcium hydroxide, metformin, cryotherapy plus calcium hydroxide, and cryotherapy plus metformin. All teeth underwent standardized two-visit root canal treatment. In the cryotherapy groups, final irrigation at the first treatment visit was performed using sterile saline at 4 °C. Spontaneous pain was assessed preoperatively and daily for 7 postoperative days using a 100-mm visual analog scale (VAS). Percussion pain was assessed preoperatively and on day 7 immediately before the second treatment visit. The effects of cryotherapy, intracanal medicament type, and their interaction were evaluated using mixed-effects modeling for spontaneous pain and analysis of covariance (ANCOVA) for day-7 percussion pain.

Conditions

Pulp Necrosis; Symptomatic Apical Periodontitis

Keywords

Periapical Periodontitis; Metformin; Calcium Hydroxide; Intracanal Cryotherapy

Outcome Measures

Primary Outcomes (1)

• Spontaneous postoperative pain on days 1 to 7

  Spontaneous postoperative pain assessed daily from day 1 to day 7 using a Visual Analog Scale (VAS). Preoperative VAS score is used as a covariate in the statistical analysis.

  Days 1 through 7 post-treatment

Secondary Outcomes (1)

• Day-7 percussion pain

  Day 7 post-treatment

Study Arms (4)

Calcium Hydroxide

ACTIVE COMPARATOR

Drug: Placement of calcium hydroxide as an intracanal medicament

Metformin

ACTIVE COMPARATOR

Drug: Placement of metformin as an intracanal medicament

Intracanal Cryotherapy and Calcium Hydroxide

ACTIVE COMPARATOR

Drug: Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapy

Intracanal Cryotherapy and Metformin

ACTIVE COMPARATOR

Drug: Application of metformin into the canal together with intracanal cryotherapy

Interventions

Placement of calcium hydroxide as an intracanal medicament DRUG

Calcium hydroxide was applied into the canal after root canal shaping

Calcium Hydroxide

Placement of metformin as an intracanal medicament DRUG

Application of metformin as an intracanal medicament following root canal shaping

Metformin

Application of metformin into the canal together with intracanal cryotherapy DRUG

Intracanal cryotherapy with 4 °C sterile saline was applied after root canal shaping and before metformin placement.

Intracanal Cryotherapy and Metformin

Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapy DRUG

Intracanal cryotherapy with 4 °C sterile saline was applied after root canal shaping and before calcium hydroxide placement.

Intracanal Cryotherapy and Calcium Hydroxide

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Systemically healthy participants. Mandibular premolar teeth diagnosed with pulpal necrosis and symptomatic apical periodontitis and indicated for root canal treatment.
• Periapical index (PAI) score of 1 or 2. Aged between 18 and 70 years. Able to understand and complete visual analog scale (VAS) assessments. Provided written informed consent.

You may not qualify if:

• Any systemic disease or pregnancy. Use of analgesics within 24 hours prior to treatment. Severe bruxism. Presence of acute apical abscess or swelling. Periodontal pocket depth greater than 5 mm or tooth mobility exceeding grade 1. Teeth deemed unrestorable. Presence of vital pulpal tissue or immature apices. Radiographic evidence of root resorption, root fracture, perforation, or canal calcification.

Sponsors & Collaborators

• Celalettin Topbaş: lead

Study Sites (1)

Saglik Bilimleri University

Istanbul, Turkey (Türkiye)

Location

Related Publications (1)

• Tan Y, Chen J, Jiang Y, Chen X, Li J, Chen B, Gao J. The anti-periodontitis action of metformin via targeting NLRP3 inflammasome. Arch Oral Biol. 2020 Jun;114:104692. doi: 10.1016/j.archoralbio.2020.104692. Epub 2020 Mar 4.

  PMID: 32305805 BACKGROUND

MeSH Terms

Conditions

Dental Pulp Necrosis; Periapical Periodontitis

Condition Hierarchy (Ancestors)

Dental Pulp Diseases; Tooth Diseases; Stomatognathic Diseases; Necrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Periapical Diseases; Jaw Diseases; Periodontal Diseases; Mouth Diseases; Periodontitis

Study Officials

• Ali O ILHAN, DDS

  Saglik Bilimleri University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and outcome assessors were masked to treatment allocation. The operator was masked to intracanal medicament assignment; however, complete operator masking to cryotherapy allocation could not be guaranteed because of the temperature difference between the irrigation solutions.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: ASSOCIATE PROFESSOR

Model Details: In this randomized, factorial (2 × 2) clinical trial, 80 patients diagnosed with symptomatic apical periodontitis in mandibular premolar teeth were included. Patients were randomly allocated to four groups: calcium hydroxide, metformin, cryotherapy + calcium hydroxide, and cryotherapy + metformin. All teeth underwent standardized two-visit root canal treatment. Postoperative pain was assessed after the first visit, and day-7 outcomes were recorded immediately before the second treatment visit.

Study Record Dates

• First Submitted: January 30, 2026
• First Posted: February 27, 2026
• Study Start: March 1, 2023
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: September 16, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data and supporting information will be available following publication of the study results. No predetermined end date is planned.
• Access Criteria: Deidentified individual participant data and supporting information may be made available to researchers who submit a reasonable request to the corresponding author. Requests will be considered in accordance with applicable ethical and institutional requirements.

Locations

TU (1)