Clinical and Radiographic Evaluation of MTA Versus Biodentine as Pulpotomy Agents in Immature First Permanent Molars: A Randomized Clinical Trial
Phase: PHASE1
Conditions: Carious Exposure of Pulp
Sponsor: Gihan M Abuelniel ,PhD

 
 
 
 
 
Clinical and Radiographic Evaluation of MTA versus Biodentine as 
Pulpotomy Agents in Immature First Permanent Molars: A Randomized 
Clinical Trial 
 
 
 
 
 
Protocol submitted to the Faculty of Dentistry, Cairo University  
by 
Dr. Gihan Abuelniel 
Associate Professor of Pediatric Dentistry 
 
Faculty of Dentistry 
Cairo University 
18 Jan 2017  
 
 
 
 
 
 
 
 
 
 
 

 
 
I. Administrative information:     
1. Title: 
   
Clinical and Radiographic Evaluation of MTA versus Biodentine as Pulpotomy 
Agents in Immature First Permanent Molars: A Randomized Clinical Trial 
 
2. Protocol Registration: 
To be registered on Clinicaltrial.gov   
  
3. Protocol version: 
Final version. 
    
4. Funding:    
This trial is self-funded.    
  
5.  Roles and responsibilities:   
1. Dr. Gihan Abuelniel (Abuelniel G.M) Associate Professor of Pediatric Dentistry, Cairo 
University. Responsible for the clinical part of study, and Data monitoring.  
2. Professor Monty Duggal (Duggal M.S) Professor of Pediatric Dentistry, National 
University of Singapore, responsible for the writing revision and proof reading. 
3. Dr. Nihal Kabel (Kabel N.R) Associate Professor of Pediatric Dentistry,
 Misr University 
for sciences and technology. Responsible for the clinical evaluation of the cases at the 
evaluation intervals 
 
II. Introduction   
6-background and rationale: 
Description of research question: 
P: children with cariously exposed immature mandibular first permanent molars 
I: Pulpotomy using Biodentine 
C: MTA pulpotomy 
O: 

 
 
 
Outcome 
Tool/Device 
Unit 
Primary Outcome 
spontaneous pain, sensitivity 
to percussion⁄ palpation) 
 
Pain questionnaire 
Binary 
Swelling or sinus tract 
Visual examination by 
the third author 
Binary 
Mobility 
Back of the mirror 
Binary 
Secondary 
outcome 
Stage of root development 
Standardized periapical 
3 stages 
Crown: Root ratio 
Standardized periapical 
2:1 
≥2:1 
Apex 
Standardized periapical 
Blunder apex, partially 
open, constricted 
Presence of 
radiolucency 
Standardized periapical 
Binary 
 
 
 
S: Randomized clinical trial 
T: 18 months (Baseline,6, 12 and 18 months) 
 
Research question: is Biodentine used as pulpotomy material in cariously exposed 
immature mandibular first permanent molars more successful clinically and 
radiographically than MTA pulpotomy? 
 
Justification for undertaking the trial: 
 
Dental caries and its tremendous effects are considered one of the greatest challenges to 
the integrity of the developing dentition.  Although the debates exist regarding the success 
rate of vital pulp therapy in cariously-exposed pulps, the technique is recommended to be 
performed on immature teeth [1,2].  
      Carious exposures in young permanent molars may cause irreversible damage to the 
pulp tissue and arrest root development, which can jeopardize the long-term tooth 
retention [3]. Hence, the main objective of treating carious-exposed immature teeth is to 

 
 
maintain pulp vitality and enhance continuation of root development and apical closure. 
This approach is called apexogenesis. [4] 
 
       Vital pulp therapies should provide a biologically conductive environment for the pulp 
tissue to regenerate and prevent future bacterial contamination by using an appropriate 
pulp-capping agent. [3] The pulp capping material should possess biocompatibility, 
bactericidal effect, ensure a biologic seal, and induce hard tissue formation. [3,5]  
 
          A new era of regenerative endodontics recommended Mineral trioxide aggregate 
(MTA), to be considered the new gold standard for vital pulp therapies, that provides long-
term seal, acceptable biocompatibility [6], and dentinal bridge formation as reported by 
various animal and human studies. [7,8] When the role of Calcium hydroxide (CH), that has 
been the most commonly used material for vital pulp therapy for many decades, was 
diminished, [9] claims raised against its use. The claims were attributed to several 
disadvantages including the exitance of tunnel defects in induced dentinal bridges, poor 
adherence to dentine, and lack of long-term seal. [10]  
     MTA is a powder that consists of fine hydrophilic particles that set in the presence of 
moisture. The setting time of MTA in moisture is less than 4h. MTA consists of tricalcium 
silicate, tricalcium aluminate, tricalcium oxide and silicate oxide. [11] MTA was considered 
a remarkable biocompatible material with various clinical applications that include surgical 
and non-surgical applications such as pulp capping [12], furcation and Perforation repairs 
[13], apexification and root end fillings [11,14]. Although the high clinical success of MTA 
material, there were always Issues prevented the clinicians to use it for many cases. The 
main reasons were related to very long setting time and difficult manipulation. [15]   
     
         Biodentine new bioactive calcium silicate-based cement has been recently launched in 
the dental market as a ‘dentin substitute’. This new biologically active material facilitates 
its penetration through opened dentinal tubules to crystallize interlocking with dentin and 
provide mechanical properties. Biodentine has been developed using MTA based cement 
technology and hence; added improved properties such as physical qualities and handling, 
and its wide range of recommended applications in endodontic repair and pulp capping. 
[16] 
    
     Radiographic imaging of the dentoalveolar complex has been assessed   using 
conventional periapical radiography, the benchmark for intraoral radiographic imaging for 
decades. Their known limitations of image magnification, distortion, superimposition and 
overlap of anatomy always led to unclear and misrepresentation of structures. Although the 
advent of digital intraoral radiography didn’t improve these limitations, it provided a more 
active image manipulation than the film-based radiographs and reduced patient exposure 

 
 
substantially. [17, 18]    
 
7 - Objectives and hypothesis: 
 
The objective of this prospective randomized clinical trial is to compare the clinical ⁄ 
radiographic outcomes of MTA and Biodentine as pulpotomy biomaterials used in 
apexogenesis treatment of symptomatic ⁄ asymptomatic vital immature mandibular 
permanent first molars with carious pulp exposure. 
 
8-Trial Design: 
 
Randomized clinical trial (RCT), parallel groups with 1:1 allocation ratio, Triple blinded (patient, 
clinical and radiographic assessor of the results and statistician) 
 
 III- Methods: 
9-Study settings: 
This study will be carried out on patients attending the outpatient clinic in Pediatric Dentistry 
department, Faculty of Dentistry, Cairo University, Egypt. the procedures will be carried out by 
Dr. Gihan Abuelniel Associate Professor of Pediatric Dentistry in Pediatric Dentistry clinic. 
expected time duration from 2017 to 2018.  
 
10- Eligibility criteria: 
Inclusion criteria:  
• Medically free children. 
• Bilaterally Symptomatic ⁄ asymptomatic vital immature mandibular first permanent 
molars (with clinical carious exposure of the pulp and presence of bleeding upon 
exposure)  
• Patients with an age range from 7-8 years. 
• Absence of sinus tract, soft tissue swelling. 
The exclusion criteria: 
• Molars were excluded if non-restorable. 
• excessive mobility (more than 1 mm horizontally). 
• Radiographic evidence of peri- and ⁄or inter-radicular lesions, internal⁄ external 
root resorption, pulp⁄ canal calcifications.   
IV- Intervention: 
Diagnosis: 

 
 
1. Full history data will be collected, including personal, medical and previous dental 
data  
2. Clinical examination using mirror and probe to assess the inclusion criteria. 
3. Radiographic examination using preoperative digital periapical radiograph to assess 
the inclusion criteria. 
4. Preoperative photograph will be taken. 
Operative procedure: 
Experimental group: 
1. Injection of local anesthesia and rubber dam isolation. 
2. caries and roof of the pulp chamber will be removed by a fissure diamond bur 
(Diatech, Heerbrug, Switzerland) and high-speed handpiece with coolant.  
3. The pulps will be amputated to the orifice level using a long-shank diamond round 
bur.  
4. Haemostasis will be achieved by gentle placement of a saline-moistened cotton pellet 
over amputated pulps for 5–10 min. 
5. Calcium silicate-based BiodentineTM (Septodont Ltd., Saint Maur des Fausse´s, 
France) will be mixed according to the manufacturer’s instructions, radicular pulp 
will be covered by the material using a wet cotton pellet. 
6.  A self-cure glass ionomer (GC; GC Corporation, Tokyo, Japan) will be placed over the 
pulpotomy agent as a final restoration.  
7.  Immediate post-operative radiograph and photograph will be taken. 
Control group: 
The same procedures will be carried out as the experimental group, but the pulp stumps 
will be covered with fast-setting mineral trioxide aggregate (MTA) ENDOCEM MTA 
(Maruchi, Wonju, Korea) and will be prepared according to the manufacturer’s 
instructions. A 3-mm-thick layer of MTA will be placed over the amputated pulps and 
will be gently adapted to the dentinal walls using a wet cotton pellet. A self-cure glass 
ionomer (GC; GC Corporation, Tokyo, Japan) will be placed over the pulpotomy agent as 
a final restoration.  
 
Postoperative care: 
Instructions to avoid lip and cheek biting in addition to oral hygiene measures. 
 
Follow up: 
Assess the outcomes clinically and radiographically at (baseline, 6, 12 and 18 months). 
 
Criteria for discontinuing or modifying intervention: 

 
 
In case of an unsuccessful outcome after pulpotomy, the molars will be managed by 
other pulp therapy techniques or extraction. 
 
 
Strategies to improve adherence to intervention: 
Explanation to the parents about the importance of follow up visits in addition to 
treatment of other dental problems. 
 
Concomitant care: 
None needed. 
12- Outcomes: 
 
Outcome 
Tool/Device 
Unit 
Primary Outcome 
spontaneous pain, 
sensitivity to percussion⁄ 
palpation) 
 
Pain questionnaire 
Binary 
Swelling or sinus tract 
Visual examination by 
the third author 
Binary 
Mobility 
Back of the mirror 
Binary 
Secondary 
outcome 
Stage of root development 
Standardized periapical 
3 stages 
Crown: Root 
ratio 
Standardized periapical 
2:1 
≥2:1 
Apex 
Standardized periapical 
Blunder apex, partially 
open, constricted 
Presence of 
radiolucency 
Standardized periapical 
Binary 
 Primary outcome: 
Clinical assessment of the findings in the table will be conducted at follow up intervals 
(baseline, 6, 12 and 18 months) 
  
Secondary outcome: 
Radiographic assessment of stage of root development, crown: root ratio, apical closure and 
presence of radiolucency will be conducted through digital periapical radiographs by parallel 

 
 
technique using film holders. The assessments will be carried out at follow up intervals 
(baseline, 6, 12 and 18 months) 
 
 
 
 
13- Participants timeline: 
 
 
Study period 
 
Enrolment  Allocation  
Post allocation 
Close out 
Time point 
For 7 
months 
0 
6 months 
12 months 
18 months 
Enrolment:  
 
 
 
 
 
Eligibility screen 
√ 
 
 
 
 
Informed consent √ 
 
 
 
 
History taking 
√ 
 
 
 
 
Clinical 
examination 
√ 
 
 
 
 
Preoperative 
radiograph 
√ 
 
 
 
 
Allocation  
 
√ 
 
 
 
Interventions: 
 
 
 
 
 
Access 
preparation 
 
√ 
 
 
 
Placement of 
Biodentine 
(experimental 
group) 
 
√ 
 
 
 
Placement of 
MTA (Control 
group) 
 
√ 
 
 
 
Final restoration 
 
√ 
 
 
 
Assessment  
 
 
 
 
 
Periapical 
radiograph as 
baseline reference 
 
 
√ 
√ 
√ 

 
 
Clinical 
examination to 
assess pain, 
swelling, fistula, 
tooth mobility 
 
 
√ 
√ 
√ 
Periapical 
radiograph to 
assess stage of 
root development, 
crown: root ratio, 
apical closure and 
presence of 
radiolucency 
 
 
√ 
√ 
√ 
 
14- Sample size calculation: 
 
   Sample size is calculated based upon the results of Alqaderi et al (2014) [15] who reported 
clinical success rate (primary outcome) for MTA = 90%. Since no relevant literature 
reported the clinical success rate of Biodentine in permanent teeth of pediatric patients, the 
success rate was assumed to be 50%. Using alpha level = 0.05 and β level = 0.20 (80% 
Power); the minimum estimated sample size will be 20 subjects per group for a total of 40 
subjects. To compensate for a drop-out rate of 15%, the number is increased to 23 subjects 
per group for a total of 46 subjects. 
Sample size calculation was performed using IBM® SPSS® Sample Power® Release 
3.0.1. 
15- Recruitment: 
 All patients attending the outpatient clinic in pediatric dentistry department 
complaining from carious mandibular first permanent molars will be screened and enrolled 
in the study if they meet the eligibility criteria. 
16- Allocation: 
Sequence generation: 
Access cavity prepared molars will be assigned into experimental or control group using simple 
randomization 1:1 by the help of the computer software(random.org). 
 
Allocation concealment mechanism: 
Numbered opaque sealed envelopes. 

 
 
 
Implementation: 
The child will choose an envelope randomly and open it after caries removal so that the operator 
knows which pulpotomy agent will be used only after finishing the access cavity. Sequence 
generation will be done by the third author and the patient assignment will be done by the 
operator. 
17- Blinding: 
Patients and their parents, the assessor and the statistician will be blinded. 
 
18- Data collection methods: 
Primary outcome: 
Clinical assessment of the following findings: 
1. postoperative pain: through asking the child and the parent if there is pain either 
continuous or intermittent  
2. Swelling: through visual examination by the assessor either intraorally or extra-orally. 
3. Sinus or fistula through visual examination of the gingiva by the assessor. 
4. Tooth mobility: By the back of the mirror checked by the assessor to detect mobility in 
any direction 
This assessment will be conducted every follow-up visit throughout the study period at baseline, 
6, 12 and 18 months. 
 Secondary outcome 
Radiographic assessment to detect stage of root development, crown: root ratio, apical closure 
and presence of radiolucency through standardized periapical radiograph by parallel technique 
using film holder. This assessment will be conducted every follow-up visit throughout the study 
period at baseline, 6, 12 and 18 months. 
Postoperative records will be performed by the assessor to avoid individual variability and to 
promote data quality. 
 
19- Data management: 
Explanation to the parents about the importance of the follow-up visits in addition to treatment 
of other dental problems are plans to promotes participants retention and complete the follow-up. 
Also, phone calls before the dates before the next follow-up visit will be scheduled. 
All findings will be documented in the examination sheet then transferred electronically to 
computer in secured lace sequentially. 
 
20- statistical methods: 
 
All data will be collected, checked, revised, tabulated and entered into the computer. 
Qualitative data will be presented as frequencies and percentages. Since the study is a split-

 
 
mouth design; Wilcoxon signed-rank test will be used to compare between the two groups. 
Friedman’s test will be used to study the changes by time within each group. Kaplan-Meier 
survival curve will be constructed to calculate the mean survival estimates of the two 
groups. Comparison between survival times will be performed using Log rank test. 
The significance level will be set at P ≤ 0.05. Statistical analysis will be performed with 
IBM® SPSS® Statistics Version 20 for Windows. 
21-Monitoring: 
The study data and results will be monitored regularly by the assessor who will have full access 
to these data. 
 
22- Harms: 
No reported adverse effects for both testing pulpotomy agents. Any adverse events appear during 
the trial will be recorded, documented and treated. 
  
23-Auditing: 
Auditing of the study design will be done by the evidence-based committee, Faculty of Dentistry 
-Cairo University. 
 
 V- Ethics and dissemination: 
 
24-Research ethics approval: 
This protocol and the template informed consent form will be reviewed by the Ethics Committee 
of Scientific Research - Faculty of Oral and Dental Medicine - Cairo University. 
 
25-Protocol amendments: 
Any modification to the protocol which may have an impact on the conduction of the study, 
potential benefit of the patient or my affect patient safety including, the changes of study 
objectives, study design, sample size or significant administrative aspects will require a formal 
amendment to the protocol. 
 
26-Consent and Assent: 
Researcher will discuss the trial with legal guardian of each participating child. They will be able 
to have an informed discussion with the researcher after explaining the procedure in simple 
words. Verbal assent will be taken orally from the participating child while written consent will 
be taken from the legal guardian f each participating child who is willing to participate in the 
                                                     
® IBM Corporation, NY, USA. 
 
® SPSS, Inc., an IBM Company. 
 

 
 
trial. All consent forms will be translated into Arabic. 
 
27-confidentiality: 
All study related information will be stored securely. All participants information will be stored 
in locked file cabinets in an area with limited access. Process and administrative forms will be 
identified by a coded ID (identification number) only to maintain participants confidentiality. All 
records that contain names or other personal identifiers will be store separately from study records 
identified by code number 
 
28-Declration of interests: 
Non-financial. 
 
29- Access to data: 
All principal investigators will be given access to the data sets. All data sets will be password 
protected. To ensure confidentiality, data dispersed to study team members will be blinded of any 
identifying participants information. 
 
30-Ancillary and post-trial care: 
Full mouth treatment will be offered to all participating children in addition to postoperative care 
and preventive measures though regular follow up visits after the end trial. 
 
31- Dissemination policy: 
-Study results and articles will be published in related journal. 
 
References: 
 
1. Miyashita H, Worthington H, Qualtrogh A, Plasschaert A. Pulp management for 
caries in adults: maintaining pulp vitality (Review). Cochrane Database Syst Rev 2007; 
18: CD004484.  
2. Waterhouse P, Whitworth J, Camp J, Fuks A. Pediatric endodontics: endodontic 
treatment for the primary and young permanent dentition. In: Hargreaves K, Cohen S. 
(eds). Pathways of the Pulp, 10th edn. St. Louis: Mosby Elsevier, 2011: 808– 857. 
3. Witherspoon D. Vital pulp therapy with new materials: new directions and treatment 
perspectives permanent teeth. J Endod 2008; 34: S25–S28.  
4.  Holland G, Trowbridge H, Rafter M. Protecting the pulp, preserving the apex. In: 
Torabinejad M, Walton R. (eds). Endodontics, Principles and Practice, 4th edn. ST. 
Louis: Saunders Elsevier, 2008: 21–38. 

 
 
5. Witherspoon D, Small J, Harris H. Mineral trioxide aggregate pulpotomies: a case 
series outcomes assessment. J Am Dent Assoc 2006; 137: 610–618. 
6. Torabinejad M, Parirokh M. Mineral trioxide aggregate: a comprehensive literature 
review – Part II: leakage and biocompatibility investigations. J Endod 2010; 36: 190–
202. 
7. Andelin W, Shabahang S, Wright K, Torabinejad M. Identification of hard tissue 
after experimental pulp capping using Dentin Sialoprotein (DSP) as a marker. J Endod 
2003; 29: 646–650.  
8. Nair P, Duncan H, Pitt Ford T, Luder H. Histological, ultrastructural and quantitative 
investigations on the response of healthy human pulps to experimental capping with 
mineral trioxide aggregate: a randomized controlled trial. Int Endod J 2008; 41: 128–
150. 
9. Stanley H. Criteria for standardizing and increasing credibility of pulp capping studies. 
Am J Dent 1998; 11S: S17–S34. 
10. Holland R, de Souza V, de Mello W, Nery M, Bernabe P, Otoboni Filho J. 
Permeability of the hard tissue bridge formed after pulpotomy with calcium hydroxide: 
a histologic study. J Am Dent Assoc 1979; 99: 472–475. 
11. Torabinejad M, Chivian N. Clinical application of mineral trioxide aggregate; J 
Endod1999;25:197-205. 
12. Pitt Ford TR, Torabinejad M, Abedi HR, Bakland LK, Kariyawasam SP. Using 
mineral trioxide aggregate as a pulp capping material. J Am Dent Assoc. 
1996;127(10):1491-94.  
13. Arens DE, Torabinejad M. Repair of furcal perforations with mineral trioxide 
aggregate: two case reports. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 
1996;82(1):84-88.  
14. Torabinejad M, Hong CU, McDonald F, Pitt Ford TR. Physical and chemical 
properties of a new root-end filling material.  J Endod. 1995;21(7): 349-53. 
15. Alqaderi HE, Al-Mutawa SA, Qudeimat MA. MTA pulpotomy as an alternative to 
root canal treatment in children’s permanent teeth in a dental public health setting. J Dent 
2014 Nov;42(11)1390-5. 
16. Kaur M, Singh H, Dhillon J S, Batra M, Saini M. MTA versus Biodentine: Review of 
Literature with a Comparative Analysis. J Clinical and Diagnostic Research. 2017 Aug, 
Vol-11(8): ZG01-ZG05. 
17. Dhir P, David CM, Keerthi G, Sharma V, Girdhar V. Digital imaging in dentistry: 
An overview. Int J Med and Dent Sci 2014; 3(2): 524-532.  
18. 
Diwakar NR, Kamakshi SS. Recent advancements in dental digital radiography. J 
Med Radiol Pathol Surg 2015; 1:11-16.