N-acetylcysteine for Root Canal Treatment of Necrotic Teeth With Apical Periodontitis (NAC)

Evaluation of N-acetylcysteine as an Intracanal and Adjunctive Systemic Medication in Root Canal Treatment of Necrotic Mature Teeth With Apical Periodontitis: a Randomized Controlled Clinical Trial

A randomized controlled trial comparing the postoperative pain intensity, periapical biomarkers level, and periapical healing in patients with necrotic mature teeth and apical periodontitis treated with N-acetylcysteine (NAC), as an intracanal and adjunctive systemic medication, versus calcium hydroxide (Ca(OH)₂) intracanal medication alone.

Study Overview

• Status: Active, not recruiting
• Conditions: Apical Periodontitis
• Intervention / Treatment: Drug: Calcium hydroxide (Ca(OH)₂); Drug: N-Acetylcysteine (NAC)

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt
    • Faculty of Dentistry, Alexandria University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Mature necrotic teeth.
• Radiographic evidence of periapical bone loss.
• Teeth that require primary endodontic treatment.
• Restorable teeth.

Exclusion Criteria:

• Immature teeth
• Teeth that had been previously accessed or endodontically treated.
• Teeth with periodontal pockets deeper than 4 mm.
• Patients with acute apical abscess.
• Patients with systemic diseases.
• Pregnant females.
• Patients who received antibiotic therapy within the past month.
• Patient on analgesics.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Calcium hydroxide (Ca(OH)₂); UltraCal XS calcium hydroxide (Ca(OH)₂) intracanal medication for 7 days	Drug: Calcium hydroxide (Ca(OH)₂); UltraCal XS calcium hydroxide (Ca(OH)₂) intracanal medication for 7 days
Experimental: N-acetylcysteine (NAC); N-acetylcysteine (NAC) intracanal medication for 7 days and 600 mg/day oral NAC for 21 days	Drug: N-Acetylcysteine (NAC); N-acetylcysteine (NAC) intracanal medication for 7 days and 600 mg/day oral NAC for 21 days; Other Names: Acetylcysteine; N-Acetyl-L-cysteine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain intensity	Postoperative pain will be assessed using the Numerical Rating Scale (NRS), which is a scale from 0 (no pain) to 10 (worst pain imaginable). Patients will be asked to choose the number that represents their pain intensity. Pain level will be assigned as follows: 0, "no pain"; 1-3, "mild pain"; 4-6, "moderate pain"; 7-10, "severe pain."	Pain will be recorded before the intervention, and patients will use the Numerical Rating Scale (NRS) to self-assess postoperative pain at 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 1 week.
Assessment of periapical healing	Assessment of the percentage change in lesion volume through three-dimensional (3D) reconstruction of the lesions in Cone beam computed tomographic (CBCT) scans performed preoperatively and after a six-month follow-up.	A CBCT scan will be taken preoperatively and at six months follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the level of periapical tissues biomarkers	The biomarker levels will be measured using enzyme-linked immunosorbent assay [ELISA]. Samples of periapical tissue fluid will be taken by inserting three sterile paper points into the root canal, about 2 mm beyond the working length, and holding them in place for 1 minute. The paper points will be transferred to a 1.5-mL Eppendorf and stored at -80°C until further analysis.	Samples will be collected from the periapical tissue fluid at two different points: before (S1) and after 7 days of administration of medications (S2).

Collaborators and Investigators

• Sponsor: Alexandria University

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: November 20, 2025
• First Submitted That Met QC Criteria: November 30, 2025
• First Posted (Estimated): December 3, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 28, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Postoperative pain; Root canal treatment; Apical periodontitis; Periapical healing; N-acetylcysteine (NAC); Cone-beam computed tomography (CBCT); Intracanal medication; Calcium hydroxide (Ca(OH)₂); Periapical tissue biomarkers
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Postoperative Complications; Pathologic Processes; Periapical Diseases; Jaw Diseases; Periodontitis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Periapical Periodontitis; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Inorganic Chemicals; Amino Acids; Anions; Ions; Electrolytes; Hydroxides; Alkalies; Cysteine; Amino Acids, Sulfur; Calcium Compounds; Acetylcysteine; Calcium Hydroxide
• Other Study ID Numbers: 9258326; PACTR202511513893768 (Registry Identifier: The Pan African Clinical Trial Registry (PACTR))

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.: Yes