Effect of Simvastatin Versus Calcium Hydroxide Intracanal Medications on Post-operative Pain and Interleukin 6 and 8

Effect of Simvastatin Versus Calcium Hydroxide Used as Intracanal Medicaments on Post-operative Pain and Total Amount of IL-6 and IL-8 in Periapical Fluids in Patients With Symptomatic Apical Periodontitis: A Randomized Clinical Trial

Comparing the effect of Simvastatin versus calcium hydroxide used as an intracanal medicament on Post-operative Pain and Total amount of IL-6 and IL-8 in Periapical Fluids of lower premolars in patients with Symptomatic Apical Periodontitis:

Study Overview

• Status: Completed
• Conditions: Periapical Periodontitis
• Intervention / Treatment: Drug: Simvastatin Powder; Drug: Calcium Hydroxide

Detailed Description

Lower premolars with symptomatic apical periodontitis will be selected according to the eligibility and exclusion criteria and patients are then randomized to receive treatment either using simvastatin or calcium hydroxide intracanal medication for 1 week. The endodontic treatment will be completed in two visits. Postoperative pain will be assessed using the Numerical Rating scale at 6, 12, 24, 48 hours post-instrumentation and at 6, 12, 24, 48 hours post-obturation. Periapical fluid sample will be collected immediately post-instrumentation and 1 week later pre-obturation. The periapical samples will be analyzed for total amounts of IL-6 and IL-8.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 52431
    • Faculty of Dentistry - Cairo University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 41 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients who are free from any physical or mental handicapping condition with no underlying systemic disease.

• Lower single rooted premolars:

  • Presence of pain with percussion.
  • Widening in the periodontal membrane space or with small sized periapical radiolucency.
  • Diagnosed clinically with symptomatic apical periodontitis.
• Patients' acceptance to participate in the trial.
• Patients who can understand pain scale and can sign the informed consent

Exclusion Criteria:

• Medically compromised patients
• Pregnant women
• Patients who are allergic to non-steroidal anti-inflammatory drugs.
• Patients with two or more adjacent teeth requiring root canal therapy
• If analgesics or antibiotics have been administrated by the patient during the past two weeks preoperatively.
• Patients reporting bruxism or clenching.
• Teeth associated with acute periapical abscess, swelling or a fistulous tract.
• Greater than grade I mobility or pocket depth greater than 5mm.
• Non restorable teeth.
• Immature teeth.
• Teeth with previous endodontic treatment.
• Radiographic evidence of external or internal root resorption vertical root fracture, perforation, calcification.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simvastatin; Simvastatin as an intracanal medication	Drug: Simvastatin Powder; Simvastatin gel placed as an intracanal medication
Active Comparator: Calcium hydroxide; Calcium hydroxide intracanal medication	Drug: Calcium Hydroxide; Calcium hydroxide intracanal medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post operative pain incidence and intensity assessed with numerical rating scale	0 (none) to 10 (severe) Numerical Pain Rating Scale	6,12,24 and 48 hours post-instrumentation and 6,12,24 and 48 hours post-obturation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total amount of IL-6 and IL-8 in periapical fluids	Absorbance using ELISA test in Pg/ml	Immediately post-instrumentation and pre-obturation (1 week post- instrumentation)

Collaborators and Investigators

• Sponsor: Cairo University

Publications and helpful links

General Publications

• Khan AA, Sun X, Hargreaves KM. Effect of calcium hydroxide on proinflammatory cytokines and neuropeptides. J Endod. 2008 Nov;34(11):1360-1363. doi: 10.1016/j.joen.2008.08.020. Epub 2008 Sep 17.
• Sharma A, Sanjeev K, Selvanathan VMJ, Sekar M, Harikrishnan N. The evaluation of cytotoxicity and cytokine IL-6 production of root canal sealers with and without the incorporation of simvastatin: an invitro study. BMC Oral Health. 2022 Jan 11;22(1):6. doi: 10.1186/s12903-022-02039-y.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Actual): June 1, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Postoperative Complications; Pathologic Processes; Periapical Diseases; Jaw Diseases; Pain, Postoperative; Periodontitis; Periapical Periodontitis; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Calcium; Simvastatin
• Other Study ID Numbers: CEBD-CU-2022-8-30

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