Effect of Propolis paste as compared to Calcium hydroxide on post-root canal treatment pain when inserted in root canals of infected teeth

ISRCTN	ISRCTN66816132
DOI	https://doi.org/10.1186/ISRCTN66816132
ClinicalTrials.gov (NCT)	NCT03723980
Protocol serial number	SMB53
Sponsor	Dow University of Health Sciences
Funder	Investigator initiated and funded

Submission date: 18/06/2017
Registration date: 24/08/2017
Last edited: 18/09/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Oral Health

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Dental pain is a significant factor that causes patient’s to seek treatment. Non-surgical endodontic (for root canals) treatment is a major therapy to treat the pain and save the tooth. Pain control during this procedure is a challenging goal for dental practitioners. Patients with necrotic teeth (when the centre part of the tooth has decayed) have the highest rates of post-endodontic pain. To prevent this, different techniques have been used. Placing biocompatible (not harmful or toxic) medications with either antimicrobial (anti- bacteria) activity or anti-inflammatory (swelling) component or both inside the root canals is one of the main techniques to disinfect the canals and control the pain. Calcium hydroxide is the most common medicament (medication mixture), however it is ineffective against certain fungi and bacteria, lacks anti-inflammatory component and is controversial in preventing pain. Presently, focus of research has shifted towards natural alternatives that could be used. Propolis is an organic resinous (thick and sticky) substance obtained from bee hive. It is nontoxic, biocompatible, anti-inflammatory, anti-oxidant, and anti-microbial and is effective against certain bacteria and fungi. The aim of this study is to evaluate the effect of Propolis paste on post-endodontic pain in comparison to calcium hydroxide at different time intervals.

Who can participate?
Adults aged 20-40 years old who have a necrotic tooth and require a root canal

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive endodontic treatment but receive a calcium hydroxide in the root area. Those in the second group receive the Propolis paste in the root area during their endodontic treatment. Participants are followed to and rate their pain levels before surgery and again four, 12, 24, 48 and 72 hours after their treatment. The two different medicaments are compared to see how well they were able to treat pain.

What are the possible benefits and risks of participating?
There are no direct benefits with participating. There are no notable risks however, participants may be allergic to the propolis paste and therefore are not included in the stufy.

Where is the study run from?
1. Dow Dental College (Pakistan)
2. Dr. Ishrat-ul-ibad Khan Institute of Oral Health Sciences (Pakistan)
3. Dow International Dental College (Pakistan)

When is the study starting and how long is it expected to run for?
January 2017 to October 2018

Who is funding the study?
Investigator initiated and funded (Pakistan)

Who is the main contact?
Dr Juzer Shabbir

Contact information

Dr Juzer Shabbir
Scientific

Dow University of Health Sciences
Dr. Ishrat-ul-ibad Khan Institute of Oral Health Sciences
Gulzar-e-Hijri
Ojha Campus
SUPARCO road
KDA Scheme-33
Karachi
75270
Pakistan

Study information

Primary study design	Interventional
Study design	Parallel group prospective double blind randomized controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effect of Propolis paste as compared to Calcium hydroxide when used as an intracanal medicament in necrotic teeth on post-endodontic pain: a double-blind randomized clinical trial
Study objectives	Null hypothesis: There will be no significant difference between Calcium hydroxide and Propolis paste in reducing and preventing post-endodontic pain. Alternative hypothesis (HA): There will be a significant difference between Calcium hydroxide and Propolis paste group in reducing and preventing post-endodontic pain.
Ethics approval(s)	Institutional Review Board, 10/03/2017, IRB-847/DUHS/Approval/2017/52
Health condition(s) or problem(s) studied	Condition as of 30/10/2018: Necrosis of pulp Previous condition: Domain in healthcare is dentistry and the condition we will be studying is Necrotic teeth with symptomatic apical periodontitis
Intervention	Interventions as of 30/10/2018: Control group: Calcium hydroxide Intervention group: Propolis paste Non-probability sampling will be done for sample recruitment and simple randomization for group allocation. Random group allocation will be computer generated. with equal randomization (1:1). The patients and the principal researcher will be blinded from the type of intracanal medicament inserted. Patient attending the diagnosis department of the hospital with complaint of pain and having necrotic teeth found on examination, requiring standard non-surgical endodontic treatment are selected by non probability sampling for the study with his/her consent. Participants are randomly allocated to one of two groups by computer generated simple randomisation. Group 1 (Control group): In the 1st visit of non surgical endodontic therapy, the standard procedure is performed until root canal preparation is completed. Then participants receive calcium hydroxide as an intracanal medicament inserted in the canal. This is supplied in a paste like consistency by the manufacturer and approximately 2.5 mg of the medication is used in each canal. This is inserted with the help of lentulo-spirals. They are only inserted once and then temporary fillings are done inside the tooth. Group 2 (Intervention group): In the 1st visit of non surgical endodontic therapy, the standard procedure is performed until root canal preparation is completed. Then participants receive Propolis paste as an intracanal medicament inserted in the canal. Propolis paste is made by mixing 200 mg of propolis powder with 0.3 ml of normal saline and then is inserted into the root canal. This is inserted with the help of lentulo-spirals. They are only inserted once and then temporary fillings are done inside the tooth.) Patients are asked to mark their pain intensity pre-operatively on Visual Analogue Scale. Then after procedure, they are given the Visual Analogue scale and requested them to mark their pain intensity (score) at 4 hours, 12 hours, 24 hours, 48 hours and 72 hours. Participants are then recalled after a week, and the Visual Analogue Scales are collected and their medicaments are removed and they proceed with their standard endodontic treatment. Previous Interventions: Control group: Calcium hydroxide Intervention group: Propolis paste Non-probability sampling will be done for sample recruitment and simple randomization for group allocation. Random group allocation will be computer generated. with equal randomization (1:1). The patients and the principal researcher will be blinded from the type of intracanal medicament inserted. Patient attending the diagnosis department of the hospital with complaint of pain and having necrotic teeth found on examination, requiring standard non-surgical endodontic treatment are selected by non probability sampling for the study with his/her consent. Participants are randomly allocated to one of two groups by computer generated simple randomisation. Group 1 (Control group): In the 1st visit of non surgical endodontic therapy, the standard procedure is performed until root canal preparation is completed. Then participants receive calcium hydroxide as an intracanal medicament inserted in the canal. This is supplied in a paste like consistency by the manufacturer and approximately 2.5 mg of the medication is used in each canal. This is inserted with the help of lentulo-spirals. They are only inserted once and then temporary fillings are done inside the tooth. Group 2 (Intervention group): In the 1st visit of non surgical endodontic therapy, the standard procedure is performed until root canal preparation is completed. Then participants receive Propolis paste as an intracanal medicament inserted in the canal. Propolis paste is made by mixing 1.5 mg of propolis powder with 1 ml of normal saline and then is inserted into the root canal. This is inserted with the help of lentulo-spirals. They are only inserted once and then temporary fillings are done inside the tooth. Participants are followed up after their first visit to mark their pain intensity (score) pre-operatively, then at four hours, 12 hours, 24 hours, 48 hours and 72 hours. Participants are then recalled after a week, and their pains scores are collected and their medicaments are removed and they proceed with their standard endodontic treatment.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Propolis paste
Primary outcome measure(s)	Primary outcome measure as of 30/10/2018: 1. Pain intensity measure: Visual Analogue Pain Scale. Difference of the pain scores between the two groups at different time intervals. Previous primary outcome measure: 1. Pain score is recorded by the patient using the Visual Analogue Scale (VAS scale) at four, 12, 24, 48 and 72 hours 2. Number of patients reaching the full followup period without taking oral analgesic is measured using the Visual Analogue Scale (statistically analysed during processing (after VAS scales are collected from all of the patients) to know how many patients reached the full follow up period of 72 hours without taking any oral analgesic) at 72 hours
Key secondary outcome measure(s)	Secondary outcome measures as of 30/10/2018: 1. Acute increase in pain score (acute exacerbation of pain), an increase of 20 or more points on Visual Analogue Pain Scale from pain score of previous time interval will indicate that pain has increased significantly and will be reported as "flare-up". 2. Difference of pain score between different time intervals will be recorded pre-operatively, then at time intervals of 4 hours, 12 hours, day 2, day 3 and day 4. The comparison of mean pain scores of different time intervals will be made. 3. Difference of pain scores and pain quality between males and females. The mean pain score difference between males and females at different time intervals will be assessed, frequencies of pain quality; no or mild pain, moderate pain, severe pain, and extreme pain will be reported according to gender. 4. Difference of pain scores and pain quality between different age groups. Mean pain score difference between different age groups: 20 to 24; 25 to 29; 30 to 34; and 35 to 40 at different time intervals will be assessed. Frequencies of pain quality; no or mild pain, moderate pain, severe pain, and extreme pain will be reported according to age group. Previous secondary outcome measures: Types of oral analgesic is measured using VAS scale (which is based on oral analgesics prescribed according to differing intensities of pain) and evaluating what type of analgesics are taken the most in each group at 72 hours
Completion date	15/10/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	80
Total final enrolment	80
Key inclusion criteria	Participant inclusion criteria as of 30/10/2018: 1. Aged 20-40 years 2. Both male and female both 3. Single rooted Necrotic teeth with symptomatic or asymptomatic periapical periodontitis having visible periapical widening or radiolucency without bone expansion (PAI index 2, 3 and 4) 4. Teeth with favorable root morphology 5. Teeth with closed apex Previous participant inclusion criteria: 1. Aged 20-40 years 2. Both male and female both 3. Single rooted Necrotic teeth with symptomatic periapical periodontitis having visible periapical widening or radiolucency without bone expansion (PAI index 3 and 4) 4. Teeth with favorable root morphology 5. Teeth with closed apex
Key exclusion criteria	Participant exclusion criteria as of 30/10/2018: 1. Teeth with PAI index 1 and 5 2. Patients who are on antibiotics 3. Patient with recent trauma to the jaw 4. Teeth with open apex 5. Multi-rooted teeth 6. Vital teeth 7. Non-restorable teeth 8. Unfavorable root morphology (severely curved, dilacerated, severely sclerosed or obliterated) 9. Teeth associated with soft tissue abscess or swelling 10. Teeth with external and internal root resorption 11. Re-treatment cases 12. Periodontally compromised teeth (like mobile teeth and teeth with excessive bone loss) 13. Teeth requiring endodontic surgery 14. Teeth requiring non-surgical endodontic treatment of multiple teeth in the same or opposing quadrant 15. Medically compromised patients (ASA-III and above), patients with special communication needs or who doesn’t understand urdu or English language 16. Patients allergic to bee pollen or honey products Previous participant exclusion criteria: 1. Teeth with PAI index 1, 4 and 5 2. Patients who are on antibiotics 3. Patient with recent trauma to the jaw 4. Teeth with open apex 5. Multi-rooted teeth 6. Vital teeth 7. Non-restorable teeth 8. Unfavorable root morphology (severely curved, dilacerated, severely sclerosed or obliterated) 9. Teeth associated with soft tissue abscess or swelling 10. Teeth with external and internal root resorption 11. Re-treatment cases 12. Periodontally compromised teeth (like mobile teeth and teeth with excessive bone loss) 13. Teeth requiring endodontic surgery 14. Teeth requiring non-surgical endodontic treatment of multiple teeth in the same or opposing quadrant 15. Medically compromised patients (ASA-III and above), patients with special communication needs or who doesn’t understand urdu or English language 16. Patients allergic to bee pollen or honey products
Date of first enrolment	01/10/2017
Date of final enrolment	24/04/2018

Locations

Countries of recruitment

Pakistan

Study participating centres

Dow Dental College

Dow University of Health Sciences
Baba-E-Urdu Road
Karachi
74200
Pakistan

Dr. Ishrat-ul-ibad Khan Institute of Oral Health Sciences

Ojha campus
University Road
Karachi
74200
Pakistan

Dow International Dental College

Korangi Road
Karachi
74200
Pakistan

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The current data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	09/01/2020	07/04/2020	Yes	No
Results article	effect of variables such as age, gender, and tooth type on postoperative endodontic pain	28/01/2021	18/09/2023	Yes	No
Basic results		30/10/2018	30/10/2018	No	No
Basic results	version v2	13/11/2018	13/11/2018	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN66816132_BasicResults_30Oct18.pdf: Uploaded 30/10/2018
ISRCTN66816132_BasicResults_v2_13Nov18.pdf.pdf: Uploaded 13/11/2018

Editorial Notes

18/09/2023: Publication reference added.
07/04/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
19/06/2019: Added ClinicalTrials.gov link to basic results (scientific).
13/11/2018: Version 2 of the basic results of this trial has been uploaded as an additional file.
31/10/2018: The clinicaltrials.gov ID was added.
30/10/2018: The following changes were made:
1. The recruitment end date was updated from 31/07/2018 to 24/04/2018.
2. The overall trial end date was updated from 31/10/2018 to 15/10/2018.
3. The ethics approval was added.
4. The condition was updated.
5. The interventions were updated.
6. The primary outcome measures were updated.
7. The secondary outcome measures were updated.
8. The participant inclusion criteria was updated.
9. The participant exclusion criteria was updated.
10. The basic results of this trial have been uploaded as an additional file.