Comparative Analgesic Effects of Paracetamol/Codeine and Ibuprofen on Pain After Third Molar Surgery

Comparative Analgesic Effects of Preoperative Administration of Paracetamol (Acetominophen) 500 mg Plus Codeine 30 mg and Ibuprofen 400 mg on Pain After Third Molar Surgery

To compare analgesic effects of preoperative administration of paracetamol 500 milligram plus codeine 30 milligram in single-tablet and effervescent formulation to ibuprofen 400 milligram, and placebo in the management of moderate to severe postoperative pain after mandibular third molar surgery.

Study Overview

• Status: Completed
• Conditions: To Control Pain After Third Molar Surgery
• Intervention / Treatment: Drug: paracetamol 500 mg plus codeine 30 mg preoperative administration; Drug: ibuprofen 400 mg preoperative administration; Drug: Placebo oral tablet preoperative administration

Detailed Description

Materials and methods: One hundred twenty healthy outpatients aged 15 to 29 years undergoing surgical removal of one bony impacted mandibular third molar were enrolled in this, single-center, prospective, randomized, triple-blind parallel-group, placebo-controlled, clinical trial. Study participants were randomly assigned to three treatment arms. According to the concealed allocation, each patient 30 minutes before surgery received paracetamol 500 mg plus codeine 30 mg (group A), ibuprofen 400 mg (group B) or placebo (group C). Rescue therapy allowed in the postoperative period was paracetamol 500 mg plus codeine 30 mg in groups A and C and ibuprofen 400 mg in group B. Patients recorded on Numerical Rating Scale-11 (NRS-11) the pain intensity, total number of postoperative-supplement medications and time of the first intake, until 12-hours after surgery and over extra two days

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00100
    • Maria Paola Cristalli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 29 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy status (ASA class I);
• nonsmoker;
• not pregnant or breastfeeding;
• no medication consumption in the past 21 days;
• good oral hygiene;
• bony impaction of one mandibular third molars;
• the presence of the first and second molars;
• compliance to cooperate with the research protocol.

Exclusion Criteria:

• chronic systemic disease;
• medications with potential interaction to paracetamol-codeine or ibuprofen;
• a history of intolerance or hypersensitivity to the study drugs;
• any pre-existing pain and acute inflammatory or infectious conditions; - inability to understand or perform the study procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Paracetamol/codeine Group A; analgesic group preoperative oral dose of paracetamol 500 mg plus codeine 30 mg	Drug: paracetamol 500 mg plus codeine 30 mg preoperative administration; each patient 30 minutes before surgery received paracetamol 500 mg plus codeine 30 mg; Other Names: GROUP A
ACTIVE_COMPARATOR: Ibuprofen Group B; analgesic group preoperative oral dose of ibuprofen 400 mg	Drug: ibuprofen 400 mg preoperative administration; each patient 30 minutes before surgery received ibuprofen 400 mg; Other Names: GROUP B
PLACEBO_COMPARATOR: Placebo Group C; Placebo group preoperative placebo	Drug: Placebo oral tablet preoperative administration; each patient 30 minutes before surgery received placebo; Other Names: GROUP C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to misure the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo in the operative day. Before surgery, patients were instructed to complete the Numerical Rating Scale-11 (NRS-11), which consisted of an interval scale ranging from 0 ("no pain") to 10 ("maximum pain")	All study participants were asked to record the pain intensity score at 1:00 pm during the operative day]
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to compare the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo in the operative day.	All study participants were asked to record the pain intensity score at 6:00 pm during the operative day]
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to compare the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo in the operative day.	All study participants were asked to record the pain intensity score at 11:00 pm during the operative day]
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to compare the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo	All study participants were asked to record the pain intensity score at 8:00 am during the 2th day after surgery]
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to compare the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo	All study participants were asked to record the pain intensity score at 1:00 pm during the 2th day after surgery]
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to compare the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo	All study participants were asked to record the pain intensity score at 6:00 pm during the 2th day after surgery]
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to compare the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo in the operative day.	All study participants were asked to record the pain intensity score at 11:00 pm during the 2th day after surgery]
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to compare the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo in the operative day.	All study participants were asked to record the pain intensity score at 8:00 am during the 3th day after surgery]
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to compare the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo in the operative day.	All study participants were asked to record the pain intensity score at 1:00 pm during the 3th day after surgery]
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to compare the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo in the operative day.	All study participants were asked to record the pain intensity score at 6:00 pm during the 3th day after surgery]
Pain measurement assessed with the Numerical Rating Scale-11 (NRS-11)	In stage 1, the objective was to compare the efficacy on pain and tolerability of a single dose of paracetamol plus codeine, ibuprofen, or placebo in the operative day.	All study participants were asked to record the pain intensity score at 11:00 pm during the 3th day after surgery]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients requiring rescue therapy	outcomes involved the number of patients requiring rescue therapy	until 12-hours after surgery and over extra two days
first postoperative use of analgesics	time of the first intake	until 12-hours after surgery
total postoperative use of analgesics	total amount of additional medication	until 12-hours after surgery and over extra two days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the efficacy of the same drugs	Patients recorded on Numerical Rating Scale-11 (NRS-11) the pain intensity	up to 48 hours after stage 1

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza
• Investigators: Principal Investigator: Maria Paola Cristalli, DDS, PhD, University of Roma La Sapienza

Publications and helpful links

General Publications

• La Monaca G, Pranno N, Annibali S, Polimeni A, Pompa G, Vozza I, Cristalli MP. COMPARATIVE ANALGESIC EFFECTS OF SINGLE-DOSE PREOPERATIVE ADMINISTRATION OF PARACETAMOL (ACETAMINOPHEN) 500 mg PLUS CODEINE 30 mg AND IBUPROFEN 400 mg ON PAIN AFTER THIRD MOLAR SURGERY. J Evid Based Dent Pract. 2021 Dec;21(4):101611. doi: 10.1016/j.jebdp.2021.101611. Epub 2021 Jul 10.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2018
• Primary Completion (ACTUAL): September 4, 2020
• Study Completion (ACTUAL): October 14, 2020

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 25, 2021
• First Posted (ACTUAL): January 29, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: postsurgical dental pain
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Acetaminophen; Ibuprofen; Codeine
• Other Study ID Numbers: 2704/2013

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