Cryotherapy and Intracanal Medicaments for Postoperative Pain in Apical Periodontitis

September 13, 2026 updated by: Celalettin Topbaş

Effect of Intracanal Cryotherapy and Metformin on Postoperative Pain in Teeth With Symptomatic Apical Periodontitis: A Randomized Clinical Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Not Applicable

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

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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.

Exclusion Criteria:

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.

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: Factorial Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Metformin
Drug: Placement of metformin as an intracanal medicament
Application of metformin as an intracanal medicament following root canal shaping
Active Comparator: Calcium Hydroxide
Drug: Placement of calcium hydroxide as an intracanal medicament
Calcium hydroxide was applied into the canal after root canal shaping
Active Comparator: Intracanal Cryotherapy and Calcium Hydroxide
Drug: Application of calcium hydroxide as an intracanal medicament together with intracanal cryotherapy
Intracanal cryotherapy with 4 °C sterile saline was applied after root canal shaping and before calcium hydroxide placement.
Active Comparator: Intracanal Cryotherapy and Metformin
Drug: Application of metformin into the canal together with intracanal cryotherapy
Intracanal cryotherapy with 4 °C sterile saline was applied after root canal shaping and before metformin placement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Spontaneous postoperative pain on days 1 to 7
Time Frame: Days 1 through 7 post-treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Day-7 percussion pain
Time Frame: Day 7 post-treatment
Percussion pain assessed on day 7 immediately before the second treatment visit using a Visual Analog Scale (VAS). Preoperative percussion VAS score is used as a covariate in the statistical analysis.
Day 7 post-treatment

Collaborators and Investigators

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

Sponsor

Celalettin Topbaş

Investigators

  • Study Chair: Ali O ILHAN, DDS, Saglik Bilimleri University

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)

March 1, 2023

Primary Completion (Actual)

January 1, 2024

Study Completion (Actual)

January 1, 2024

Study Registration Dates

First Submitted

January 30, 2026

First Submitted That Met QC Criteria

February 21, 2026

First Posted (Actual)

February 27, 2026

Study Record Updates

Last Update Posted (Actual)

September 16, 2026

Last Update Submitted That Met QC Criteria

September 13, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BSL5R6DP90

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified individual participant data underlying the results reported in the publication may be made available by the corresponding author upon reasonable request, subject to applicable ethical and institutional requirements.

IPD Sharing Time Frame

Data and supporting information will be available following publication of the study results. No predetermined end date is planned.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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