The Effects of Preemptive Multimodal Analgesic on Endodontic Pain Following Root Canal Therapy.

NCT07400471 | Recruiting Early Phase 1 DMC

• 1 other identifier: ERC-BBS/2025/0015-44/2025
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

A clinical trial comparing preemptive multimodal analgesics with placebo in the management of immediate and chronic post-endodontic pain. The study utilizes statistical methods such as chi-squared, T-tests, and regression analysis, accounting for multiple outcomes with the Bonferroni adjustment. Duloxetine hydrochloride and pregabalin, both available in Bangladesh, are evaluated as experimental drugs, while placebos are used to assess psychological effects on pain. All participants receive standard interventional treatments, with acetaminophen provided as needed, and ethical considerations are addressed according to international guidelines.

Conditions

Post Endodontic Pain; Mechanical Detection Threshold; Mechanical Pain Threshold; Mechanical Pain Sensitivity

Keywords

post endodontic pain; Root canal Therapy; Multimodal Analgesia; Dynamic sensory test

Outcome Measures

Primary Outcomes (1)

• Effects of Preemptive multimodal analgesia on post endodontic pain

  Primary Pain during endodontic treatment and the effectiveness of intervention will be evaluated at 6, 12, 24, 48, 72, and hourly intervals after the endodontic procedure. Treatment-related anaesthetic efficacy will be assessed using the VAS (Visual Analogue Scale; numerical value 0-10). During endodontic treatment, the level of pain will decide how effective the anesthetic is. The patient will be asked to rate the analgesic effects on a VAS (Visual Analogue Scale) scale by providing a numerical number 0-10. '0" are indicated no pain, 1-3= mild pain, 4-6= moderate pain, 7-10= sever pain.

  6, 12, 24, 48, 72 hours

Secondary Outcomes (3)

• Mechanical Detection Threshold

  baseline, 72 hours

• Mechanical Pain Threshold

  baseline, 72 hours

• Mechanical Pain Sensitivity

  baseline, 72 hours

Study Arms (2)

Multimodal Analgesia

ACTIVE COMPARATOR

Preemptive Multi modal analgesic drug: Experimental group will be divided into 2 subgroups according to use of drug. A. Pregabalin-acetaminophen. B. Duloxetine-Acetaminophen Pregabalin-acetaminophen: Before a half-hour endodontic treatment, patients in this group will receive a single dosage of 50 mg pregabalin and 500 mg acetaminophen. If necessary, acetaminophen dosages of 500 mg will be administered three times a day. Duloxetine-Acetaminophen: Prior to a half-hour endodontic treatment, patients in this group will receive a single dosage of 500 mg of acetaminophen and 30 mg of Duloxetine. If necessary, acetaminophen dosages of 500 mg will be administered three times a day.

Drug: Pregabalin- Acetaminophen; Drug: Duloxetine- Acetaminophen

Control

PLACEBO COMPARATOR

Placebo: Patient in this group will receive placebo drug before half an hour of operating procedure. If necessary, acetaminophen dosages of 500 mg will be administered three times a day and noted

Drug: Pregabalin- Acetaminophen; Drug: Duloxetine- Acetaminophen

Interventions

Pregabalin- Acetaminophen DRUG

Preemptive Multi modal analgesic drug: Experimental group will be divided into 2 subgroups according to use of drug. A. Pregabalin-acetaminophen. B. Duloxetine-Acetaminophen Pregabalin-acetaminophen: Before a half-hour endodontic treatment, patients in this group will receive a single dosage of 50 mg pregabalin and 500 mg acetaminophen. If necessary, acetaminophen dosages of 500 mg will be administered three times a day.

Control; Multimodal Analgesia

Duloxetine- Acetaminophen DRUG

Duloxetine-Acetaminophen: Prior to a half-hour endodontic treatment, patients in this group will receive a single dosage of 500 mg of acetaminophen and 30 mg of Duloxetine. If necessary, acetaminophen dosages of 500 mg will be administered three times a day.

Control; Multimodal Analgesia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient's aged 18 years more.
• ASA physical status I-II.
• Patient with the complain of pain originated from teeth and surrounding structure.
• Preoperative pain severity is moderate to severe.
• Patient can be able to make communication about their pain.
• Patients give consent to attain this research.
• Patients have others concomitant chronic pain.
• Patients who will have non-surgical endodontic treatment.
• Patients who will have non-surgical endodontic retreatment.
• Patients who will have surgical endodontic treatment.

You may not qualify if:

• Patient would not like to attain in research.
• Patients have any medical condition those are contra indication for study drug.
• ASA physical status III, IV, V.
• Patient already under treated any anti convulsent drug.
• Patient participant in other clinical trials.
• Lack of motivation or poor adharence to study protocols.
• Patient with Pregnancy
• Severe organ dysfunction
• Patient have Hepatitis B, and other cross infection disease like (HIV)
• Uncontrolled comorbidities that patient do not fit for endodontic treatment.
• Severe cognitive impaired patients.
• History of certain cancers or severe hematological issues.

Sponsors & Collaborators

• Chattogram International Dental College: lead

Study Sites (1)

Professor. Dr. Md. Abu Saeed Ibn Harun

Chittagong, Chattogram, 4212, Bangladesh

RECRUITING

Related Publications (23)

• Anibal Diogenes, Michael A. Henry. Pain Pathways and Mechanisms of the Pulpodentin Complex. Chapter 8; Seltzer and Bender's Dental Pulp. 2nd edition. Quintessence Publishing Co Inc;2012.

  BACKGROUND

• Jang YE, Kim Y, Kim BS. Influence of Preoperative Mechanical Allodynia on Predicting Postoperative Pain after Root Canal Treatment: A Prospective Clinical Study. J Endod. 2021 May;47(5):770-778.e1. doi: 10.1016/j.joen.2021.01.004. Epub 2021 Jan 29.

  PMID: 33516824 BACKGROUND

• Alelyani AA, Azar PS, Khan AA, Chrepa V, Diogenes A. Quantitative Assessment of Mechanical Allodynia and Central Sensitization in Endodontic Patients. J Endod. 2020 Dec;46(12):1841-1848. doi: 10.1016/j.joen.2020.09.006. Epub 2020 Sep 15.

  PMID: 32941893 BACKGROUND

• Wiech K, Ploner M, Tracey I. Neurocognitive aspects of pain perception. Trends Cogn Sci. 2008 Aug;12(8):306-13. doi: 10.1016/j.tics.2008.05.005. Epub 2008 Jul 5.

  PMID: 18606561 BACKGROUND

• Md. Abu Saeed Ibn Harun et al. The dimension and severity of orofacial pain in patients with current and chronic odontogenic pain. M Dent J 2021; 41(3): 235-244.

  BACKGROUND

• Woolf CJ. Windup and central sensitization are not equivalent. Pain. 1996 Aug;66(2-3):105-8. No abstract available.

  PMID: 8880830 BACKGROUND

• Md. Abu Saeed Ibn Harun et al. Endogenous Pain modulation of Irreversible Pulpitis and Persistent Endodontic Pain. Chattagram International Dental College Journal 2019; 2(1):9-13.

  BACKGROUND

• O'Keefe EM. Pain in endodontic therapy: preliminary study. J Endod. 1976 Oct;2(10):315-9. doi: 10.1016/S0099-2399(76)80047-7. No abstract available.

  PMID: 1068208 BACKGROUND

• Doleman B, Leonardi-Bee J, Heinink TP, Boyd-Carson H, Carrick L, Mandalia R, Lund JN, Williams JP. Pre-emptive and preventive NSAIDs for postoperative pain in adults undergoing all types of surgery. Cochrane Database Syst Rev. 2021 Jun 14;6(6):CD012978. doi: 10.1002/14651858.CD012978.pub2.

  PMID: 34125958 BACKGROUND

• Price DD, Finniss DG, Benedetti F. A comprehensive review of the placebo effect: recent advances and current thought. Annu Rev Psychol. 2008;59:565-90. doi: 10.1146/annurev.psych.59.113006.095941.

  PMID: 17550344 BACKGROUND

• Ince B, Ercan E, Dalli M, Dulgergil CT, Zorba YO, Colak H. Incidence of postoperative pain after single- and multi-visit endodontic treatment in teeth with vital and non-vital pulp. Eur J Dent. 2009 Oct;3(4):273-9.

  PMID: 19826598 RESULT

• Al-Nahlawi T, Alabdullah A, Othman A, Sukkar R, Doumani M. Postendodontic pain in asymptomatic necrotic teeth prepared with different rotary instrumentation techniques. J Family Med Prim Care. 2020 Jul 30;9(7):3474-3479. doi: 10.4103/jfmpc.jfmpc_342_20. eCollection 2020 Jul.

  PMID: 33102316 RESULT

• Nixdorf DR, Moana-Filho EJ, Law AS, McGuire LA, Hodges JS, John MT. Frequency of persistent tooth pain after root canal therapy: a systematic review and meta-analysis. J Endod. 2010 Feb;36(2):224-30. doi: 10.1016/j.joen.2009.11.007.

  PMID: 20113779 RESULT

• Oshima K, Ishii T, Ogura Y, Aoyama Y, Katsuumi I. Clinical investigation of patients who develop neuropathic tooth pain after endodontic procedures. J Endod. 2009 Jul;35(7):958-61. doi: 10.1016/j.joen.2009.04.017.

  PMID: 19567314 RESULT

• Hargreaves KM, BermanLH, Cohen S. Cohen's Pathways of the Pulp. 11th ed. Amsterdam, Netherlands: Elsevier; 2015.

  RESULT

• Santos-Puerta N, Penacoba-Puente C. Pain and Avoidance during and after Endodontic Therapy: The Role of Pain Anticipation and Self-Efficacy. Int J Environ Res Public Health. 2022 Jan 27;19(3):1399. doi: 10.3390/ijerph19031399.

  PMID: 35162422 RESULT

• Smith EA, Marshall JG, Selph SS, Barker DR, Sedgley CM. Nonsteroidal Anti-inflammatory Drugs for Managing Postoperative Endodontic Pain in Patients Who Present with Preoperative Pain: A Systematic Review and Meta-analysis. J Endod. 2017 Jan;43(1):7-15. doi: 10.1016/j.joen.2016.09.010. Epub 2016 Dec 6.

  PMID: 27939729 RESULT

• Suneelkumar C, Subha A, Gogala D. Effect of Preoperative Corticosteroids in Patients with Symptomatic Pulpitis on Postoperative Pain after Single-visit Root Canal Treatment: A Systematic Review and Meta-analysis. J Endod. 2018 Sep;44(9):1347-1354. doi: 10.1016/j.joen.2018.05.015. Epub 2018 Jul 24.

  PMID: 30054100 RESULT

• Zanjir M, Sgro A, Lighvan NL, Yarascavitch C, Shah PS, da Costa BR, Azarpazhooh A. Efficacy and Safety of Postoperative Medications in Reducing Pain after Nonsurgical Endodontic Treatment: A Systematic Review and Network Meta-analysis. J Endod. 2020 Oct;46(10):1387-1402.e4. doi: 10.1016/j.joen.2020.07.002. Epub 2020 Jul 12.

  PMID: 32668310 RESULT

• Mazaleuskaya LL, Theken KN, Gong L, Thorn CF, FitzGerald GA, Altman RB, Klein TE. PharmGKB summary: ibuprofen pathways. Pharmacogenet Genomics. 2015 Feb;25(2):96-106. doi: 10.1097/FPC.0000000000000113. No abstract available.

  PMID: 25502615 RESULT

• Compound Summery Acetaminophen. National Library of Medicine. Seen 2023. www.pubchem.ncbi.nlm.nih.gov.

  RESULT

• Park SJ, Zhang S, Chiang CY, Hu JW, Dostrovsky JO, Sessle BJ. Central sensitization induced in thalamic nociceptive neurons by tooth pulp stimulation is dependent on the functional integrity of trigeminal brainstem subnucleus caudalis but not subnucleus oralis. Brain Res. 2006 Sep 27;1112(1):134-45. doi: 10.1016/j.brainres.2006.06.115. Epub 2006 Aug 22.

  PMID: 16930568 RESULT

• 37. Harun, A. S. I. harun, Hossain, . A., Jabber, S. and Hasan, H. . (2021) "The dimension and severity of orofacial pain in patients with current and chronic odontogenic pain", Mahidol Dental Journal. Bangkok, Thailand, 41(3), pp. 235-244. available at: https://he02.tci-thaijo.org/index.php/mdentjournal/article/view/251124 (accessed: 3 June 2025).

  RESULT

Central Study Contacts

Prof.Dr. Md. Abu Saeed Ibn Harun, MS

CONTACT

8801711157586; dr.abusaeed@cidch.edu.bd

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Consequently, triple binding is ensured (by the sit investigator, patient, and operator). The statistician in charge of the data analysis will also be blind.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 10, 2026
• Study Start: February 6, 2026
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)