Clinical and Microbiological Evaluation of the Chemo-mechanical Caries Removal Agent (BRIX3000®) in Primary Molars: A Randomized Controlled Clinical Trial.
Phase: NA
Conditions: Dental Caries
Sponsor: King Abdulaziz University

 
 
Study Protocol and Statistical Analysis Plan  
 
 
Official Title:  
Clinical and Microbiological Evaluation of the Chemo-
mechanical Caries Removal Agent (BRIX3000®) in 
Primary Molars: A Randomized Controlled Clinical 
Trials. 
 
NCT number: 
Not available yet 
 
Date of the document: 
20/09/2019 
 
 
 
 
 
 

 
 
Clinical and Microbiological Evaluation of the Chemo-mechanical Caries 
Removal Agent (BRIX3000®) in Primary Molars: A Randomized Controlled 
Clinical Trial. 
 
 التقييم السريري
والميكروبيولوجي للعامل الكيميائي- الميكانيكي 
( إلزالة تسوس األسنان®
BRIX3000
 )
 في األضراس األولية: تجربة سريرية
محكمة عشوائية. 
 
By 
Manal S. Maashi 
BDS, 2004; MSc,2012 
Thesis Proposal Submitted in Partial Fulfillment of the Requirement for the Degree of 
Doctor of Philosophy in Pediatric Dentistry (PhD) 
 
 
Supervised by: 
Dr. Heba Elkhodary 
Prof. Dr.  Najlaa Alamoudi 
 
 
Faculty of Dentistry 
King Abdulaziz University 
2018-2019 
 

 
 
Table of Contents 
Research Problem ......................................................................................................................... 1 
Literature Review  ........................................................................................................................ 3 
Importance of the Research ......................................................................................................... 7 
Research Objectives ...................................................................................................................... 9 
Hypothesis .................................................................................................................................... 10 
Research Materials and Methods .............................................................................................. 11 
Research Limitations .................................................................................................................. 22 
Structure of the Research ........................................................................................................... 23 
Thesis Plan ................................................................................................................................... 24 
Expected Findings ....................................................................................................................... 25 
References .................................................................................................................................... 26 
 
 
 
 
 
 
 
 
 
 

4 
 
RESEARCH PROBLEM 
Dental caries is one of the most prevalent chronic diseases of people worldwide. It results in 
localized dissolution and destruction of the calcified tooth tissues (Selwitz et al., 2007). Dental 
caries has been considered as a great challenge for the dentist, as they seek for efficient means to 
control it. The destruction to the dental structure does not develop as a result of localized 
accumulation of bacteria, rather it is an invasive and infectious process, which result from the 
interaction of multiple inter-related factors (Lima et al., 2005). The “caries-affected” dentine is 
described as demineralized inter-tubular dentin, crystal deposition in dentinal tubules, lesser 
amount of destructed collagen matrix with no bacterial invasion. On the contrary, the “caries-
infected” dentine displays deformation of the microstructure of the dentinal tubules, 
permanently-damaged collagen fibers with significant penetration of the bacteria. Thus, the 
“caries-infected” dentine has to be removed only during caries removal (Hamama et al., 2014). 
 
Traditional clinical treatment of dental decay has developed on the basis of removal of 
carious tissues with high-speed handpieces and slow-rotating instruments inducing pain, 
disturbing sounds and vibrations. In addition, this method comprises the tooth structure by 
removing both “caries-affected dentin” and “caries-infected tissues” (Jawa et al., 2010).The 
concept of minimal intervention dentistry includes the selective removal of caries-infected tissue 
with preserving the healthy caries-affected tissue that have the ability of remineralization. The 
use of chemo-mechanical caries removal is one of the main implementations of the minimum 
intervention dentistry idea accepted in the last ten years. “Chemo-mechanical caries removal” 
requires the chemical mellowing of decayed dentin then its elimination by light removal using 
hand instruments (Hamama et al., 2014).  Chemo-mechanical caries removal differs from the 
conventional surgical by that it selectively removes carious dentine thereby it is less destructive 
and less painful promoting a positive attitude of visiting dentists among the children (Goomer et 

5 
 
al., 2013). Investigations are required to evaluate and compare the outcome of two chemo-
mechanical agents (BRIX3000®) and (Carie-Care™) versus conventional surgical methods. 
Therefore, the present study aims to perform clinical and microbiological evaluation of caries 
removal using (BRIX3000®) and (Carie-Care™) versus conventional surgical methods in primary 
molars among children in Jeddah city, Saudi Arabia.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

6 
 
LITERATURE REVIEW 
Rotary systems including high- and low-speeds air rotors are usually used for caries removal. 
Theses rotary devices has the advantage of rapid caries removal. However, it has the disadvantage 
of jeopardizing the healthy tooth structure, uncomfortable, and the possibility of pulpal injury as 
a result of heat and pressure created during preparation (Maragakis et al., 2001).   
Novel techniques have been developed as alternatives to conventional methods for caries 
removal in pediatric dentistry. The chemo-mechanical caries removal technique though it is more 
comfortable it requires more time with anticipation to conventional surgical methods for caries 
access and finishing the preparation (Soni et al., 2015). Several “chemo-mechanical caries 
removal agents” have been developed in the market since 1975. They can be generally 
categorized into either sodium hypochlorite (GK-101, GK-101E, Caridex®, Cariosolv®) (Fig.1) 
or enzyme-based agents (Papacárie®, Carie-Care™, Brix3000®) (Fig.2) (Hamama et al., 2014, 
Venkataraghavan et al., 2013, Felizardo et al., 2018). 
Many investigations have compared the efficacy, time taken, and pain threshold of different 
chemo-mechanical agents versus the conventional surgical method.  
Regarding the efficacy of caries removal, Goomer et al. (2013) concluded that chemo-
mechanical method for removal of decay with Cariosolv was less effective than traditional 
surgical technique though it was a worthwhile alternative to the painful procedures; like drilling, 
especially among children, who are afraid of dentists. These results were confirmed by other 
studies conducted by “Pandit et al. (2007), Bohari et al. (2012) and Soni et al. (2015)”. Other 
studies conducted by “Fure et al. (2000), Banerjee et al. (2000), Bergmann et al. (2005), Lozano-
Chourio et al. (2006), Peric et al. (2009) and Almaz et al. (2016), Kochhar et al. (2011)” showed 
that surgical and chemo-mechanical method exhibits similar efficacy to remove caries. 

7 
 
Maragakis et al. (2001) and Yazici et al. (2005) concluded that Cariosolv could not be an 
alternative to surgical method since the caries was not removed completely. 
Regarding the time taken of caries removal, several studies found that chemo-mechanical 
methods needed significantly greater time compared to surgical caries removal. This is most 
likely because chemo-mechanical agents usually require frequent implementation for caries 
removal (Goomer et al., 2013, Soni et al., 2015, Banerjee et al., 2000, Pandit et al., 2007, Kochhar 
et al., 2011, Maragakis et al., 2001, Fure et al., 2000, Bergmann et al., 2005, Lozano‐Chourio et 
al., 2006, Peric et al., 2009). 
Regarding the pain experienced during caries removal, several studies concluded that 
chemo-mechanical caries removal is more accepted, less painful technique of caries removal 
allowing patient to participate positively during dental treatment compared to the surgical method 
(Soni et al., 2015, Goomer et al., 2013, Pandit et al., 2007, Kochhar et al., 2011, Rafique et al., 
2003). This finding could be attributed to many factors. Anusavice and Kincheloe (1987) 
explained absence of pain or mild pain sensation associated with chemo-mechanical caries 
removal because only carious dentin is removed in contrast to the conventional surgical method 
that includes removal of both sound and carious dentin. In addition, chemo-mechanical agents 
are available in form of gel covering the cavity that can provide thermal insulation during the 
caries removal. Meanwhile, no vibration or heat generation during the use of chemo-mechanical 
method resulting in no or little opening of dentinal tubules that can be account for minimal pulpal 
response. Munshi et al. (2002) mentioned that chemo-mechanical caries removal does not 
persuade pain and anxiety because it does not call for the use of local anesthesia thus avoiding 
the trauma associated with the injection and the fear of the needle. 
 
 

8 
 
 
 
 
 
 
 
 
Figure 1: Sodium hypochlorite-based chemo-mechanical caries removal agents. 

9 
 
 
 
 
 
 
 
 
 
 
 
Figure 2: Enzyme-based chemo-mechanical caries removal agents. 

10 
 
IMPORTANCE OF THE RESEARCH 
The disadvantages accompanied with the use of the conventional surgical method of caries 
removal has been overcome by the use of “chemo-mechanical caries removal method”. “Chemo- 
mechanical caries removal” is one of the minimally invasive techniques that found to be less 
painful, less destructive and more accepted by children (Goomer et al., 2013, Soni et al., 2015). 
In addition to these advantages, the research holds clinical significance as a novel agent for 
“chemo-mechanical caries removal” (BRIX3000®) by the laboratory Brix Medical Science. It 
has been released recently in the dental market in 2015. It is a papain-based gel derived from 
leaves latex and fruits of green papaya (Carcia Papaya) that works as chemical debridement. It is 
for atraumatic caries removal with unique technology Encapsulating Buffer Emulsion (EPE) 
(Felizardo et al., 2018). This technology, according to the manufacture, provides the product 
with: 
1. Proteolytic enzymatic activity that differs than previous products (Carie-Care) in the 
amount of papain used (3,000 U/mg in a concentration of 10%). 
2. Perfect pH that solidifies the enzymes and set them free instantly on the collagen through 
its proteolytic activity.  
3. Stable in room temperature with no need to be refrigerated with increased its shelf-life up 
to 48 months.  
4. Increased enzymatic selectivity to damaged collagen. 
5. Reduced time needed for removing the damaged dentinal tissues.  
6. Enhanced the antifungal, antibacterial, and antiseptic ability.  
7. Increased roughness to the cavity floor that favored better adhesion of the restoration.  
By reviewing the literature, there are limited studies concerning its implementation in the 
area of pediatric dentistry. Clinical and microbiological studies are needed to confirm 

11 
 
manufacturer’s claims by comparing this novel chemo-mechanical agent (BRIX3000®) and the 
previously-available chemo-mechanical agent (Carie-Care™) to the conventional surgical 
method for caries removal. Therefore, the purpose of this research is to perform clinical and 
microbiological evaluation of caries removal using these three different methods of caries 
removal in primary molars.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

12 
 
RESEARCH OBJECTIVES 
1) 
To compare the efficacy of the chemo-mechanical method (BRIX3000®, Carie-Care™) 
versus the conventional surgical method in decreasing the cariogenic bacteria in dentine caries 
of primary molar teeth in vivo. 
2) 
To compare the efficiency of the chemo-mechanical method (BRIX3000®, Carie-Care™) 
versus the conventional surgical method in caries removal of primary molar teeth in vivo. 
3) 
To compare the pain experienced by children during dental treatment with the chemo-
mechanical method (BRIX3000®, Carie-Care™) versus the conventional surgical method in 
caries removal of primary molar teeth in vivo. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

13 
 
HYPOTHESIS 
The null hypothesis for this research will be as follows: 
There is no difference in the efficacy, efficiency and pain experienced between chemo-
mechanical caries removal agents (Brix3000®), (Carie-Care™) and the conventional surgical 
methods in primary molars. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

14 
 
RESEARCH MATERIALS AND METHODS 
 
This study will be will be carried out at King Abdulaziz Dental University Hospital 
(KADUH) and at Microbiology Research Laboratory in the Faculty of Pharmacy, King 
Abdulaziz University in Jeddah, Saudi Arabia to evaluate the efficacy, efficiency, pain 
experienced by children with the use of the chemo-mechanical method (BRIX3000®) and (Carie-
Care™) versus the conventional surgical method in primary molars. 
 
Materials: 
Ethical Approval 
The study was approved by the “Research Ethics Committee” at Faculty of Dentistry, King 
Abdulaziz University (KAU), under approval number 107-06-19. 
 
Informed Consent 
Written informed consent will be received from the parents or the guardians of the children after 
explaining the research procedures to them. 
 
Subjects (sampling) 
The study sample will consist of healthy and cooperative children between the ages of 4-9 years 
with bilateral open occlusal carious lesions in primary molars, who will attend as outpatients to 
the Department of Pediatric Dentistry at KADUH during the period from October 2019 to 
October 2020. 
 
Inclusion criteria: 

15 
 
• Healthy and cooperative patients of age group 4-9 years. 
• Primary first/second molars with open occlusal carious lesion having moderated depth 
and clinically visible brownish color softened dentin. 
• No clinical signs or symptoms of pulp degeneration, such as tenderness to percussion and 
history of sinus tracts or swelling. Intraoral periapical radiographs with lesions having 
radiolucency extending into, but only confined to dentin. 
 
Exclusion Criteria: 
• Patients with any major and minor systemic illness. 
• Uncooperative patients that necessitate pharmacological dental treatment. 
• Primary molars with mobile teeth, arrested caries, restored teeth, non-vital teeth, no 
carious lesion, presence of developmental defects and non-restorable teeth. 
• Patients on any antibiotic regimen either on the day of treatment or for at least 2 weeks 
prior to the study. 
• Patients allergic to Latex. 
• Radiographic evidence of external or internal root resorption, furcal or periapical 
radiolucency. 
• Primary molars with more than half of the root length resorbed. 
• Children who did not attend and complete the second session of treatment. 
• Not approving to sign the consent. 
Sample Size Calculation: 
The sample size was measured using G power analysis for calculating estimated sample size. 
Based on the results of Bohari et al. 2012, it was found that 30 subjects per group were required 

16 
 
to detect a statistically significant difference between the two groups anxiety score (FLACC) 
with a power of 95% at the significance level of 0.05. 
 
The study group will be consisted of 120 primary molars with bilateral design from 60 children 
aged 4-9 years without sex predilection. The included teeth will be assigned randomly into one 
of the following groups according to the decay removal technique that will be utilized using two-
arm parallel groups with split-mouth design: 
The control group (A): (n=60) primary molars will be subjected to removal of caries using a 
conventional drilling method using carbide dental burs. 
The test group (B): (n=30) primary molars will be subjected to removal of caries using a chemo-
mechanical agent (Brix3000®, Brix Medical Science, Carcarañá-Santa Fe, Argentina). 
The test group (C): (n=30) primary molars will be subjected to removal of caries using a chemo-
mechanical agent Carie-Care™, Uni-Biotech Pharmaceuticals Private Limited, Chennai, India in 
collaboration with Vittal Mallya Scientific Research Foundation). 
 
Armamentarium & Equipment  
1) Basic dental examination Kit 
2) Restorative kit 
3)  Brix3000® “Brix Medical Science, Carcarañá-Santa Fe, Argentina” 
4) Carie-Care™ “Uni-Biotech Pharmaceuticals Private Limited, Chennai, India in 
collaboration with Vittal Mallya Scientific Research Foundation”. 
5)  Dental bur “Low-Speed Tungsten Carbide round bur US-NO 1-8, Meisinger, USA. 
L.L.C., Easter Avenue Centennial, Colorado; High-Speed Diamond round medium size 
08-018, Meisinger, USA. L.L.C., Easter Avenue Centennial, Colorado” 

17 
 
6)  Rubber dam kit. 
7)  Sterile vial. 
8) Bacteriological incubator 
9)  Inoculation loop. 
10) Blood agar plates “Schaedler agar” 
11)  GC Fuji IX GP®. 
12) A Stop Watch. 
 
Methods: 
Study design 
Experimental, randomized controlled clinical trial with two-arm parallel groups and bilateral 
design following the “Consolidated Standards of Reporting Trials (CONSORT,2010)” 
statement (Fig.3). 
 
Randomization 
Since bilateral technique will be utilized in both parallel groups, it was decided to start on the 
right side irrespective of the method assigned by randomization. To control the variable of the 
side favored by the clinician, the researchers will make sure that each side is treated evenly by 
both methods using block randomization. Before recruiting participants, 60 sealed envelopes 
containing the randomization results will be arranged, sealed and mixed blindly in a box. Each 
envelope represents a block of the two contralateral teeth. The envelopes will be numbered 
blindly from 1 to 60. Each envelope will be opened immediately before starting the procedure on 
the right side. 
 

18 
 
 

19 
 
Clinical Procedures 
The degree of dental destruction will be clinically determined by using a dental probe. Only 
open occlusal cavities with brown and softened dentin with broadly comparable depth exhibiting 
frank moderate cavitation will be chosen “severe decay, stage 5, ICDAS [International Caries 
Detection and Assessment System]” (Ismail et al., 2007, Dikmen, 2015). The depth of caries 
progression will be confirmed with an intraoral periapical radiograph such that radiolucency did 
not involve the pulp.  
To assess the efficacy of caries removal in all groups, the outer surface of the decayed lesion 
will be washed with sterile normal saline (5 mL) to avoid contamination of plaque bacteria before 
taking the sample. The first sample will be taken from superficial carious lesion with the aid of 
a sterile sharp spoon excavator (Size #4; Nordent Manufacturing Inc., Bonnie Lane, Elk Grove 
Village, IL, USA). After completing caries removal, the cavity will be washed with sterile normal 
saline (5 mL) and dried with a sterile cotton pellet. A second sample of dentin will be taken from 
different sites of the cavity including the walls and floor using a sterile sharp spoon excavator 
(Size #4; Nordent Manufacturing Inc., Bonnie Lane, Elk Grove Village, IL, USA). The first and 
second samples will be collected in screw cap sterile vials containing 1 ml of isotonic saline for 
microbiological evaluation. Following decay elimination by both techniques, cavities will be 
filled using Glass Ionomer restoration (GC Fuji IX GP®) according to manufacturer’s 
instructions. For Microbiological cultivation and evaluation, dentin samples of all groups will be 
processed in the Advanced Techniques Laboratory in Dental research within 2 hours of 
collection. The samples will be vortexed for 30 sec to remove the microorganisms from dentin. 
The samples will be then regularly watered to obtain a 104, and a sterile loop full of sample (0.1 
ml) will be collected and cultured with aseptic technique onto blood agar plates (Schaedler agar) 
by streaking method. Then, the plates will be incubated aerobically at 35oC for 24 hours. Using 

20 
 
colony counter, the total viable count (TVC) will be obtained and expressed as colony forming 
units “CFU” per ml of sample. 
To determine the efficiency of caries removal in all groups, time will be recorded in seconds 
by using a stopwatch from the beginning of caries removal till the cavity is certain to be caries-
free. 
To assess the pain experienced throughout caries removal in all groups, the “Wong-Baker 
FACES® Pain Rating Scale” (Wong & Baker, 1988) will be utilized (Fig. 4).  
Dental treatment will be accomplished according to the following steps: 
• 
Local anesthesia will be used for all groups. 
• 
Rubber dam isolation will be used for all groups. 
• 
Caries removal will be done utilizing one of the 3 techniques as follows: 
 
The Control Group: Caries removal using “conventional drilling method” 
Caries removal will be carried out using a sterile Tungsten carbide round bur “US-NO 1-8, 
Meisinger, USA. L.L.C., Easter Avenue Centennial, Colorado” on micromotor handpiece at 
slow speed (6000-8000 rpm) without water spray. If necessary, undermined enamel will be 
removed with rotary cutting bur in high speed to enlarge the cavity and provide an adequate 
access to remove all softened dentin tissue beneath. After caries removal, dentin will be 
considered caries free utilizing visual and tactile clinical criteria. 
 
 
 
 

21 
 
The Experimental Group (BRIX-3000): Caries removal using “chemo-mechanical agent” 
(Brix3000®) 
According to manufacturer’s instructions, the restorative procedure will be performed without 
anesthesia under partial isolation with cotton rolls according to the principles of “Atraumatic 
Restorative Treatment (ART)”. Then, the papain-based gel BRIX 3000® will be applied to the 
cavity with double-ended dental spoon excavator (Size #2, #3, #4; Nordent Manufacturing Inc., 
Bonnie Lane, Elk Grove Village, IL, USA) leaving it to act for 2 minutes. After 1 minute, the 
formation of oxygen will be observed and the gel will be turned from translucent green color to 
cloudy. Then, the infected tissues will be removed through curettage by dental spoon excavator 
with pendulum movement without pressure, first at the surrounding walls followed by pulp wall 
removal. After the gel removal, the cavity will be rinsed with water and dried using mild air blow. 
The cavity will then be evaluated for any residual softened dentin tissue. The procedure could be 
repeated by applying BRIX3000® as many times as required to remove all of the infected carious 
tissue. The presence of healthy dentin will be confirmed when (the gel is no longer changed in 
color and turned turbid. The cavity will be examined according to visual “absence of any 
discoloration” and tactile “smooth passage of explorer and absence of a catch or tug back 
sensation” clinical criteria using a dental explorer. Caries will be regarded to be totally removed 
when the explorer did not stick in dentin and gave no tug back sensation. If necessary, 
undermined enamel will be removed with rotary cutting bur in high speed “round medium 
diamond bur size 08-018, Meisinger, USA. L.L.C., Easter Avenue Centennial, Colorado” to 
enlarge the cavity and provide an adequate access to remove all softened dentin tissue beneath.  
 
The Experimental Group (Carie-Care): Caries removal using “chemo-mechanical agent” 
(Carie-Care™) 

22 
 
The carious cavity will be treated with Carie-Care™ “Uni-Biotech Pharmaceuticals Private 
Limited, Chennai, India in collaboration with Vittal Mallya Scientific Research Foundation”. 
Following the instructions of the manufacturer, the Carie-Care™ gel will be brought to room 
temperature. The gel will be left in the carious lesion for 60 seconds. At that time, the appearance 
of the gel will be changed from translucent into cloudy. Then the gel will be removed with 
moistened cotton pellet and softened carious dentin will be scrapped off using spoon excavator 
((Size #2, #3, #4; Nordent Manufacturing Inc., Bonnie Lane, Elk Grove Village, IL, USA). The 
process will be redone till consecutive administration of the gel was unsuccessful to turn into 
cloudy. Decay removal will be verified by probing with dental explorer (visual-tactile clinical 
criteria). 
 
Statistical Analysis 
The statistical assessment will be carried out using Statistical Package for Social Sciences 
(SPSS, V.20, IBM; Armonk, NY, USA). Analysis of data will be done through measuring p-
value to determine statistical significance. The level of significance will be set at 0.05 (p-value 
of less than 0.05 was considered statistically significant). Various statistical methods will be used 
for measuring p-value depending whether the data will be normally distributed (parametric) or 
not normally distributed (non-parametric). For normally distributed data, paired sample t-test and 
independent sample t-test will be used. For non-normally distributed data, Wilcoxon signed rank 
test and Mann Whitney U test will be used. 

23 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 4: Wong-Baker FACES® Pain Rating Scale. 
 

24 
 
RESEARCH LIMITATIONS 
 
Although, the chemo-mechanical methods cannot eliminate the dental caries completely, it 
tends to follow the principles of minimal intervention dentistry approaches. The generalization 
of results is one of the expected limitations of this research. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

25 
 
STRUCTURE OF THE RESEARCH 
 
The research will be divided into several chapters: 
• Chapter 1 will represent the introductory note on the state of dental caries among children 
and treatment approaches that are extensively used by the dentists including different 
chemo-mechanical agents used. 
• Chapter 2 will present the literature review for the study. 
• Chapter 3 will depict the methodology for the research. It will provide in-depth 
explanation of the materials and methods used for gathering data regarding different 
treatment modalities used in this research. 
• Chapter 4 will illustrate the results attained from this research. 
• Chapter 5 will provide the discussion of findings on the basis of results obtained in the 
research. 
• Chapter 6 will sum up the entire results with general conclusions, evaluation of 
hypothesis, policy implications, and recommendations. 
 
 
 
 
 
 
 
 
 
 

26 
 
THESIS PLAN 
 
 
 
 
  
STEPS OF PhD THESIS 
TIME FRAME (MONTH) 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Application of CONSORT Statement 
2010 
X 
 
 
 
 
 
 
 
 
 
 
 
Proposal writing 
 
X 
 
 
 
 
 
 
 
 
 
 
Proposal presentation 
 
 
X 
 
 
 
 
 
 
 
 
 
Discussion with the statician 
 
X 
 
 
 
 
 
 
 
 
 
 
Ethical approval 
 
 
 
X 
 
 
 
 
 
 
 
 
Registration 
 
 
 
 
X 
 
 
 
 
 
 
 
Apply for funding 
 
 
 
 
X 
X 
 
 
 
 
 
 
Providing tools and materials 
 
 
 
 
 
 
X 
 
 
 
 
 
Intervention for in-vivo study 
 
 
 
 
 
 
X 
X 
X 
 
 
 
Intervention for in-vitro study 
 
 
 
 
 
 
X 
X 
X 
 
 
 
Data analysis 
 
 
 
 
 
 
 
 
X 
X 
X 
 
Thesis writing 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Thesis defense  
 
 
 
 
 
 
 
 
 
 
 
X 

27 
 
EXPECTED FINDINGS 
 
The findings may show an increased efficacy, efficiency with decreased pain experienced 
during caries removal of chemo-mechanical method using newly developed agent (Brix3000®) 
as the manufacturer company claimed compared to the previously-available (Carie-CareTM) and 
to the conventional surgical method. It may be recommended as an alternate treatment modality 
among children, who fear to visit clinics for getting dental treatments. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

28 
 
REFERENCES 
Almaz ME, Sonmez IS, Oba AA (2016). Comparison of chemomechanical caries removal 
using Papacárie versus conventional method in children. European Journal of General 
Dentistry. 5(1): 1. Doi: 10.4103/2278-9626.172734. 
 
Anusavice KJ, Kincheloe JE (1987). Comparison of pain associated with mechanical and 
chemomechanical removal of caries. J Dent Res.66:1680–1683. 
 
Anwar AS, Kumar RK, Rao VAP, Reddy NV, Reshma VJ (2017). Evaluation of 
microhardness of residual dentin in primary molars following caries removal with 
conventional and chemomechanical techniques: An In vitro Study. Journal of pharmacy & 
bioallied sciences. 9(1): S166. Doi: 10.4103/jpbs.jpbs_148_17 
 
Arora R, Goswami M, Chaudhary S, Chaitra TR, Kishor A and Rallan M (2012). 
Comparative evaluation of effects of chemo-mechanical and conventional caries removal on 
dentinal morphology and its bonding characteristics - an SEM study. Eur Arch Paediatr Dent 
13: 179-184. 
 
Bergmann J, Leitão J, Kultje C, Bergmann D and Clode MJ (2005). Removing dentine caries 
in deciduous teeth with Carisolv: a randomised, controlled, prospective study with six-month 
follow-up, comparing chemomechanical treatment with drilling. Oral health & preventive 
dentistry 3: 105-111. 
 
Bohari MR, Chunawalla YK, Ahmed BMN (2012). Clinical Evaluation of Caries Removal 
in Primary Teethusing Conventional, Chemomechanical and LaserTechnique: An in vivo 
Study. The Journal of Contemporary Dental Practice. 13(1): 40-47. Doi: 10.5005/jp-journals-
10024-1093 
 
Botelho Amaral FL, Martao Florio F, Bovi Ambrosano GM and Basting RT (2011). 
Morphology and microtensile bond strength of adhesive systems to in situ-formed caries-
affected dentin after the use of a papain-based chemomechanical gel method. American 
journal of dentistry 24: 13-19. 

29 
 
 
Cardoso PEC, Moura S, Júnior M, Gomes W and Santos JFF (2001). Caries removal: SEM 
analysis. Journal of Dental Research 80: 75. 
 
Cederlund A, Lindskog S and Blomlöf J (1999). Efficacy of Carisolv-assisted caries 
excavation. International Journal of Periodontics & Restorative Dentistry 19. 
 
Corrêa FN, Rodrigues Filho LE and Rodrigues CR (2008). Evaluation of residual dentin after 
conventional and chemomechanical caries removal using SEM. J Clin Pediatr Dent 32: 115-
120. 
 
Dikmen B (2015). Icdas II Kriterleri (Uluslararası Çürük Tespit ve Değerlendirme Sistemi) 
ICDAS II Criteria (International Caries Detection And Assessment System). 
 
Erhardt MCG, Toledano M, Osorio R and Pimenta LA (2008). Histomorphologic 
characterization and bond strength evaluation of caries-affected dentin/resin interfaces: 
effects of long-term water exposure. Dental Materials 24: 786-798. 
 
Felizardo KR, de Alvarenga Barradas NP, Guedes GF, Ferreira FdCA and Lopes MB (2018). 
Use of BRIX-3000 Enzymatic Gel in Mechanical Chemical Removal of Caries: Clinical Case 
Report. Journal of Health Sciences 20: 87-93. 
 
Fure S, Lingstrom P and Birkhed D (2000). Evaluation of Carisolv for the chemo-mechanical 
removal of primary root caries in vivo. Caries research 34: 275-280. 
 
Gianini RJ, do Amaral FL, Florio FM and Basting RT (2010). Microtensile bond strength of 
etch-and-rinse and self-etch adhesive systems to demineralized dentin after the use of a 
papain-based chemomechanical method. American journal of dentistry 23: 23-28. 
 
Goomer P, Jain RL, Kaur H and Sood R (2013). Comparison of the efficacy of 
chemicomechanical caries removal with conventional methods - a clinical study. Journal of 
international oral health : JIOH 5: 42-47. 

30 
 
 
Haak R, Wicht MJ and Noack MJ (2000). Does chemomechanical caries removal affect 
dentine adhesion? Eur J Oral Sci 108: 449-455. 
 
Hamama H, Yiu C and Burrow M (2014). Current update of chemomechanical caries 
removal methods. Australian dental journal 59: 446-456; quiz 525. 
 
Hosoya Y, Kawashita Y, Marshall Jr G and Goto G (2001). Influence of Carisolv™ for resin 
adhesion to sound human primary dentin and young permanent dentin. Journal of Dentistry 
29: 163-171. 
 
Ismail A, Sohn W, Tellez M, Amaya A, Sen A, Hasson H and Pitts N (2007). The 
International Caries Detection and Assessment System (ICDAS): an integrated system for 
measuring dental caries. Community dentistry and oral epidemiology 35: 170-178. 
 
Jawa D, Singh S, Somani R, Jaidka S, Sirkar K and Jaidka R (2010). Comparative evaluation 
of the efficacy of chemomechanical caries removal agent (Papacarie) and conventional 
method of caries removal: an in vitro study. Journal of the Indian Society of Pedodontics and 
Preventive Dentistry 28: 73-77. 
 
Kochhar GK, Srivastava N, Pandit IK, Gugnani N and Gupta M (2011). An evaluation of 
different caries removal techniques in primary teeth: a comparitive clinical study. The Journal 
of clinical pediatric dentistry 36: 5-9. 
 
Kotb RM, Elkateb MA, Ahmed AM, Kawana KY and El Meligy OA (2016). Dentin 
Topographic Features following Chemomechanical Caries Removal in Primary Teeth. The 
Journal of clinical pediatric dentistry 40: 472-479. 
 
Kumar KS, Prasad MG, Sandeep RV, Reddy SP, Divya D, Pratyusha K. (2016). 
Chemomechanical caries removal method versus mechanical caries removal methods in 
clinical and community-based setting: A comparative in vivo study. European journal of 
dentistry. 10(3): 386. Doi: 10.4103/1305-7456.184151. 

31 
 
Lima GQT, Oliveira EG, Souza JILD, Monteiro Neto V. (2005). Comparsion of the efficacy 
of chemomechanical and mechanical methods of caries removal in the reduction of 
Streptococcus mutans and Lactobacillus spp in carious dentine of primary teeth. Journal of 
Applied Oral Science 13(4): 399-405. Doi: 10.1590/s1678-77572005000400016 
 
Lozano‐Chourio M, Zambrano O, González H and Quero M (2006). Clinical randomized 
controlled trial of chemomechanical caries removal (Carisolv™). International journal of 
paediatric dentistry 16: 161-167. 
 
Maragakis GM, Hahn P and Hellwig E (2001). Clinical evaluation of chemomechanical 
caries removal in primary molars and its acceptance by patients. Caries research 35: 205-
210. 
 
Munshi AK, Hegde AM, Shetty PK (2001). Clinical evaluation of carisolv in the chemo-
mechanical removal of carious dentine. J Clin Pediatr Dent.26(1):49–54. 
 
Pandit IK, Srivastava N, Gugnani N, Gupta M and Verma L (2007). Various methods of 
caries removal in children: a comparative clinical study. Journal of the Indian Society of 
Pedodontics and Preventive Dentistry 25: 93-96. 
 
Peric T, Markovic D and Petrovic B (2009). Clinical evaluation of a chemomechanical 
method for caries removal in children and adolescents. Acta Odontologica Scandinavica 67: 
277-283. 
 
Rafique S, Fiske J and Banerjee A (2003). Clinical trial of an air-
abrasion/chemomechanical operative procedure for the restorative treatment of dental 
patients. Caries research 37: 360-364. 
Selwitz RH, Ismail AI and Pitts NB (2007). Dental caries. The Lancet 369: 51-59. 
 
Soni HK, Sharma A and Sood PB (2015). A comparative clinical study of various methods 
of caries removal in children. European Archives of Paediatric Dentistry: official journal of 
the European Academy of Paediatric Dentistry 16: 19-26. 

32 
 
Venkata Raghavan K, Kush A, Lakshmi Narayana C, Diwakar L, Ravikumar P, Patil S and 
Karthik S (2013). Chemomechanical Caries Removal: A Review & Study of an 
Indigenously Developed Agent (Carie Care TM Gel) In Children. Journal of international 
oral health: JIOH 5: 84. 
 
Wong DL and Baker CM (1988). Pain in children: comparison of assessment scales. 
Pediatric nursing 14: 9-17.