The Success and Survival of Teeth and Restoration Following Root Canal Treatment With Varying Degrees of Tooth Structure Loss Restored With CAD CAM Restorations.
Conditions: Dental Pulp Diseases
Sponsor: King's College London

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PROTOCOL TITLE:  
“The survival of teeth and/or restoration following root canal treatment with varying 
degrees of tooth structure loss restored with CAD CAM restorations” 
 
Sponsor 
Name: King’s College London 
Address: James Clerk Maxwell Building, 57 Waterloo Road, London, SE1 8WA 
Chief Investigator  
Name: Prof. Francesco Mannocci (1st Academic Supervisor) 
Address: King's College London Dental Institute 
                Floor 25, Tower Wing 
                Guy's Dental Hospital 
                London Bridge 
                London, UK. 
                SE1 9RT 
Telephone: 020718881573 
Email: francesco.mannocci@kcl.ac.uk 
 
Name and address of Co-Investigator(s), Statistician, Laboratories etc 
Name:     Mohamed Noushad Rahim (PhD Student) 
Address:  King's College London Dental Institute 
                Biomaterials, Biomimetics & Biophotonics Research Group 
                Floor 17, Tower Wing 
                Guy's Dental Hospital 
                London Bridge 
                London, UK. 
                SE1 9RT 
 
Telephone: 07525178209 
Email: mohamed.rahim@kcl.ac.uk 
 
 

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Name: Dr. Rupert Austin(2nd Academic Supervisor) 
Address:  King's College London, Dental Institute 
                Biomaterials, Biomimetics & Biophotonics Research Group 
                Floor 17, Tower Wing 
                Guy's Dental Hospital 
                London Bridge 
                London, UK. 
                SE1 9RT 
 
Email: rupert.s.austin@kcl.ac.uk 
 
Name: Mr. Manoharan Andiappan (Statistician) 
Address:  Floor 18, Tower Wing 
                Guy's Dental Hospital 
                London Bridge 
                London, UK.                 
                SE1 9RT 
Telephone: 020 7188 8091 
Email: manoharan.1.andiappan@kcl.ac.uk 
 
 
 
 
 
 
 
 
 
 
 
 
 

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CONTENTS 
 
 
1. Background & Rationale................................................................................................. 5 
2 Trial Objectives, Design and Statistics ............................................................................ 7 
2.1. Trial Objectives ............................................................................................................ 7 
2.2 Trial Design & Flowchart ............................................................................................. 7 
2.3 Trial Flowchart.............................................................................................................. 8 
2.4 Trial Statistics ............................................................................................................ ...9 
2.4.1 Sample Size ............................................................................................................... .9 
2.4.2 Recruitment and Retention.........................................................................................9 
2.4.3 Randomisation ......................................................................................................... 10 
2.4.4 Analysis.................................................................................................................... 10 
3 Selection and Withdrawal of Subjects ........................................................................... 10 
3.1 Inclusion Criteria ........................................................................................................ 10 
3.2 Exclusion Criteria ....................................................................................................... 11 
3.3 Withdrawal of Subjects ............................................................................................... 11 
4 Assessment of Efficacy .................................................................................................. 11 
4.1 Efficacy Parameters .................................................................................................... 11 
4.1.1 Primary Efficacy Parameters ................................................................................... 11 
4.1.2 Secondary Efficacy Parameters ............................................................................... 11 
4.2 Procedures for Assessing Efficacy Parameters ........................................................... 12 
5 Assessment of Safety ..................................................................................................... 12 
6. Definition of the End of Trial..............................................………………………......13 
7. Direct Access to Source Data and Documents ............................................................. 13 
8. Ethics and Regulatory Approvals ................................................................................. 13 
9. Quality Assurance, Data Handling, Publication Policy and Finance............................ 14 
10. References....................................................................................................................14 
 
 
 
 
 

 
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Study Synopsis 
 
Title of clinical trial 
 
 
 
 
The success and survival of teeth and restoration 
following root canal treatment with varying degrees 
of tooth structure loss restored with CAD CAM 
restorations. 
 
Protocol Short Title/Acronym 
 
 
Survival of root canal treated tooth restored using 
ceramic onlays 
Sponsor name 
 
 
King’s College London 
Chief Investigator 
 
 
Prof. Francesco Mannocci 
REC number 
 
 
17/NW/0594 
Medical condition or disease under 
investigation 
 
Investigation of endodontically treated teeth’s 
success and survival rate at 1-2 years post treatment. 
Purpose of clinical trial 
 
 
To compare the success and survival rate of 
endodontically treated teeth and restoration with 
varying degrees of tooth structure loss restored with 
CAD CAM restorations 
Primary objective 
 
 
To investigate whether varying amounts of residual 
tooth structure have an influence on the success and 
survival rate of endodontically treated teeth and 
restoration at 1-2 years post treatment restored using 
CAD CAM restorations 
Secondary objective (s) 
 
 
To assess the survival of the CAD CAM restorations 
on root canal treated teeth and determine the main 
types of failure. 
 
Trial Design  
 
 
Case control 
Sample Size 
 
 
120patients 
Summary of eligibility criteria 
 
 
Patients either male or female over the age of 18 in 
good general health needing root canal treatment. 
 
Version and date of final protocol 
 
 
Version 1.6 date: 29-06-2017 

 
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1. Background & Rationale 
 
Enlargement and shaping of the root canal space are the main objectives of root canal 
treatment, then sealing it in 3 dimensions to avoid any infection in the future [1, 2]. Wide 
range of instruments and techniques have been used to accomplish root canal treatment 
[3].  
Although initial root canal therapy has been shown to be a predictable procedure with a 
high degree of success [4-7], failures can occur after treatment. Recent publications 
reported failure rates of 14%–16% for initial root canal treatment [4, 6-8].  
Lack of healing is attributed to persistent intraradicular infection residing in previously 
uninstrumented canals, dentinal tubules, or in the complex irregularities of the root canal 
system [9-12]. The extraradicular causes of endodontic failures include periapical 
actinomycosis [13], a foreign body reaction caused by extruded endodontic materials [14, 
15], an accumulation of endogenous cholesterol crystals in the apical tissues [16], and an 
unresolved cystic lesion [17, 18]. The preferred treatment of failing endodontic cases is 
nonsurgical retreatment. According to [6, 19-22] this treatment usually results in 
successful outcomes. 
Conflicting results are present in the literature in relation to the survival of endodontically 
re-treated teeth. Well controlled trials at 4 years [23] did not find any significant 
difference between survival of root canal treated and root canal re-treated teeth, whereas 
the comparison of epidemiologic studies conducted on the survival of teeth following 
primary and secondary endodontic treatment in dental practices [7, 24] shows that many 
more re-root canal treated teeth are extracted in the long term. The only information 
available on the effect of the restoration type on the survival or re-root canal treated teeth 
is that teeth restored with a cast restoration and teeth not requiring a post for the retention 
of the crown survive longer. Advances in technology, materials and techniques offer 
more contemporary ways to restore endodontically treated teeth. One of them is the 
computer aided design and computer aided manufacturing of ceramic onlays and crown. 
While this is an established and successful treatment for vital teeth, there are no 
randomised clinical trials showing its efficacy in endodontically treated teeth. 

 
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Cone beam computed tomography (CBCT) is a contemporary, radiological imaging 
system designed specifically for use on the maxillofacial skeleton. The system overcomes 
many of the limitations of conventional radiography by producing undistorted, three-
dimensional images of the area under examination. These properties make this form of 
imaging particularly suitable for use in endodontics [25]. Recent laboratory and clinical 
investigations have revealed that periapical disease may be detected sooner using CBCT 
compared with periapical views and the true size, extent, nature and position of periapical 
and resorptive lesions can be assessed [26]. 
This CBCT study will compare the success and survival rate of endodontically treated 
teeth with varying degrees of tooth structure loss restored with CAD CAM (Computer 
Aided Design Computer Aided Manufacturing) restorations, which are routinely used for 
the clinical care of patients. 
This will be carried out at KCL Dental Institute at Guy's Hospital and will form part of 
the routine dental treatment done at the dental clinics. Potential volunteers will be given 
written information about the process (see attached information sheet) and be given time 
to consider participation. Once any questions have been answered, fully informed written 
consent will be obtained if they are interested in taking part.  
Patients requiring endodontic treatment with varying degrees of tooth structure loss will 
be detected and diagnosed and treated by endodontic MclinDent postgraduate students at 
Guy’s hospital using suitable clinical techniques. 
Immediately after root canal treatment has been completed and at patients’ review 
appointments in addition to the conventional radiograph we would also take an additional 
specialised 3-dimensional Cone Beam Computed Tomography (CBCT) scan of the tooth. 
Clinical evaluation and radiographic assessment including dental periapical radiograph 
and Cone Beam Computed Tomography (CBCT) scans will be done at baseline, 12 
months and 24 months. 
There are no side effects of taking part in this study other than those expected from 
exposure to ionising radiation taken during routine operative dental care. Every exposure 
to ionising radiation carries a risk, but due to the low doses of radiation from dental 
radiology including CBCT, this risk is negligible. The effective dose of a conventional 
radiograph and a cone beam computed scan is 5 μSv and 66 μSv (micro Sieverts) 
respectively, equivalent to 0.19% and 2.43% annual background radiation respectively.  

 
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The total radiation dose corresponds to approximately 28 days equivalent natural 
background radiation, where background radiation is approximately 2.7 mSv per year in 
the UK. 
This clinical trial will be conducted in compliance with the principles of the Declaration 
of Helsinki. The protocol will be submitted for approval to an NHS Research Ethics 
Committee. 
2. Trial Objectives, Design and Statistics 
2.1. Trial Objectives 
 
Aims and Objectives: 
The clinical trial aims to investigate whether varying amounts of residual tooth structure 
have an influence on the success and survival rate of endodontically treated teeth and/or 
restoration at 1-2 years post treatment by using Cone Beam Computed Tomography 
(CBCT). 
Primary and Secondary endpoints: 
The principal outcome of the study is to assess the success and survival of endodontically 
treated teeth and restoration at 1 and -2 years post treatment restored using CAD CAM 
restorations. The secondary outcome measure is to assess the survival of the CAD CAM 
restorations on root canal treated teeth and determine the main types of failure. 
2.2 Trial Design & Flowchart 
 
The study is a case control comparing the success and survival rate of endodontically 
treated teeth with varying degrees of tooth structure loss restored using CAD CAM 
restorations. 
Patients requiring endodontic treatment will be assessed clinically and radiographically 
and divided into groups defined according to the residual coronal dentin after root canal 
treatment into four groups (less than 33% , 33%-50%, 50%-66% and more than 66% of 
tooth structure remaining).  The endodontic treatment and final restoration will be 
accomplished 
by 
Endodontic 
MclinDent 
Postgraduates 
Students 
(Endodontic 
Postgraduate Unit, Guy’s Hospital, Guy’s & St. Thomas’ NHS trust) who will be trained 

 
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to ensure standardisation of the endodontic and operative procedures by using one of the 
indirect/direct restorations. 
Dental periapical radiograph and Cone Beam Computed Tomography (CBCT) scans will 
be taken at baseline, 12 months and 24 months. The patients will be sent a reminder to 
attend the follow up by email, letter or SMS. Clinical assessment and radiographical 
evaluation of Cone Beam Computed Tomography (CBCT) scans will be carried out 
immediately after endodontic treatments have been accomplished and 1 and 2 years post 
operatively and will be assessed independently by a group of examiners. 
Four examiners (Endodontists n=2, Radiologists n=2) will view the randomised images 
under standardised conditions. The examiners will also be trained on how to interpret 
CBCT data before looking at images. The restorations will be assessed clinically. 
 
2.3 Trial Flowchart:- 
 
STUDY FLOWCHART  
 
 
 
 
 

 
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2.4 Trial Statistics 
2.4.1 Sample Size 
The sample size calculation for this study was based on chi-test for testing the association 
between tooth surface lost (<33%, 33-66% and >66%) and Root Canal Treatment status 
(Success or Failure). A study with an effect size of 0.3 and a power of 80% will require a 
total sample of 108 to test the association at 5% levels using two tailed test. The power 
calculation was carried out using Gpower 3.1.7. 
 
In a previous study by Ferrari et al. (2012), a sample of 345 patients provided 6 groups of 
60 premolars each in need of endodontic treatment. Groups were classified according to 
the number of remaining coronal walls before abutment build-up. Within each group, 
teeth were allocated to one of three subgroups: (A) no post retention; (B) prefabricated 
post; or (C) customized posts (N = 20). The authors found that failure risk was lower in 
teeth restored with prefabricated (p = 0.001) than with customized posts (p = 0.009). 
Teeth with one (p = 0.004), two (p < 0.001), and three coronal walls (p < 0.001) had 
significantly lower failure risks than those without ferrule and similar failure risks existed 
for teeth without coronal walls, regardless of the presence/absence of ferrule (p = 0.151). 
Sample size calculation for this study was based on comparing success rates for the four 
groups using chi-square test. This study designed to have 80% power to detect the 
difference in success rates between the four groups at 5% level of significance with an 
effect size of 0.35 using a two-tailed test. Assuming a dropout rate of 25% at the end 
(after 2 years of root canal re-treatment), it requires a sample size of 120 
 
2.4.2 Recruitment and Retention 
Patients who have been referred to the Endodontic Postgraduate Unit or assessment 
clinics at King’s College Dental Institute at Guy’s Hospital for root canal treatment will 
first undergo an examination at the assessment clinic to diagnose and treatment plan their 
problem by the postgraduate students under supervision of the Consultants in charge of 
the Endodontic clinic. This is to check if the tooth is indicated for root canal treatment or 
extraction.  

 
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If they are indicated for root canal treatment and satisfies the inclusion criteria of the 
clinical trial, they will be given the invitation letter and Patient Information Sheet.  
They then have about two weeks, before their scheduled appointment to decide if they 
want to take part in the study or not. If they express an interest, at this appointment, they 
will then be explained the study by the treating post graduate student, who is part of the 
research team and thereby begin the informed consent process. Consented patients will be 
allocated an anonymised number. 
If they do not wish to take part, they will still receive routine treatment as planned at the 
assessment clinic 
2.4.3 Randomisation 
Randomisation is not applicable, as the patients will be divided according to the number 
of tooth structure lost. 
2.4.4 Analysis 
Descriptive statistics will be used to summarise the sample characteristics and baseline 
measurements. Chi square test for association will be used to test whether there is any 
relationship between success rate and different groups. The difference in success rate 
over a period of time will be analysed using survival analysis. This will involve Kaplan-
Meier graph and cox regression predictors of failure rate. All analysis will be carried out 
by using SPSS version 20.  
3. Selection and Withdrawal of Subjects 
3.1 Inclusion Criteria  
 
1) Patients either male or female over the age of 18 (who can consent for themselves) in  
good general health.  
2) The selected teeth needed to be in occlusal function with a natural tooth and in 
interproximal contact with two adjacent natural teeth. 
 

 
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3) Molar or premolar teeth with suspected endodontic problems that require root canal 
treatment.  
4) Teeth should not be mobile and must be restorable. 
3.2 Exclusion Criteria  
1) Pregnant women, in view of requirements for radiographs (or if they could possibly be 
pregnant). To be confirmed by the Medical History Questionnaire. 
2) Patients younger than 18. 
3) Patients unable to give consent. 
4) Teeth with probing periodontal depths greater than 5 mm. 
5) Non-restorable teeth. 
6) Not involving patients from prisons. 
7) Not involving patients who cannot read, write or understand English 
3.3 Withdrawal of Subjects  
 
The participant would be withdrawn from the study if he or she no longer wishes to 
participate in the study or has relocated and will be unable to attend. Data or tissue, which 
is not identifiable to the research team, may be retained. Any identifiable data or tissue 
would be anonymised or disposed of. 
4. Assessment of Efficacy  
4.1 Efficacy Parameters 
Parameters used to assess efficacy of the study will depend upon the participant’s signs 
and symptoms, clinical examination and radiographical assessment. 
4.1.1 Primary Efficacy Parameters 
The primary efficacy parameter will be the success of teeth in relation to the absence of any 
signs and symptoms, endodontic or restorative failures. 
4.1.2 Secondary Efficacy Parameters 
The survival of teeth and or restoration in the oral cavity.  

 
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4.2 Procedures for Assessing Efficacy Parameters 
 
Patients will be recalled after 12 and 24 months for clinical and radiographical 
assessments. Four examiners other than the operator independently performed evaluation 
of success or failure. 
Clinical examination should reveal the absence of the following events which considered 
if present as ‘relative’ failures: restoration debonding, restoration fracture, failure of the 
core portion requiring a new coronal restoration, and no mobility of the teeth or 
tenderness to percussion. While root fractures leading to tooth extraction were considered 
as ‘absolute’ failures. 
CBCT scans assessment should reveal the absence or reduction of any radiolucencies or 
widening of the apical periodontal ligament space and vertical or horizontal root fracture.  
5. Assessment of Safety  
 
5.1 Specification, Timing and Recording of Safety Parameters  
Measures that will be taken to ensure the subject’s safety during the study are the same as 
with any routine dental procedure. 
 
5.2 Adverse Event (AE)- Any untoward medical occurrence in a subject to whom a 
medicinal product has been administered, including occurrences which are not 
necessarily caused by or related to that product 
 Syncope/ transient loss of consciousness during dental procedure or medical 
emergencies of a mild nature that are managed at chair side. 
 
5.3 Adverse Drug Reaction (ADR) - Any untoward and unintended response in a subject 
to an investigational medicinal product which is related to any dose administered to that 
subject.  
 Sodium hypochlorite used in root canal treatment is known to cause an adverse 
reaction of pain/ swelling if accidently extruded beyond the root apex. These are 
rare and not expected to be reported 
 
5.4 Serious Adverse Event or Reaction (SAE/SAR) - A serious adverse event is defined 
as an adverse experience that results in any of the following outcomes:-  
 death   
 a life-threatening adverse experience (any adverse experience that places the 
patient or subject, in the view of the investigator, at immediate risk of death from 
the reaction as it occurred, i.e., it does not include a reaction that, had it occurred 
in a more severe form, might have caused death)  
 inpatient hospitalisation or prolongation of existing hospitalization  
 a persistent or significant disability/incapacity (a substantial disruption of a 

 
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person's ability to conduct normal life functions)'  
 a congenital anomaly/birth defect. 
 
Where GSTT is the Sponsor and the SAE is related (that is, it resulted from 
administration of any of the research procedures), to the study procedures or is an 
unexpected occurrence (that is, the type of event is not listed in the protocol as an 
expected occurrence) then it must be reported immediately upon knowledge of the event 
to R&D and always within 24 hours. For all other AEs these must be reported to GSTT 
when copied into the Annual Progress Report. 
 
The definition of “serious” may be defined differently within the protocol and it is the 
responsibility of the research team to adhere to the protocol definition in terms of SAE 
reporting. Additionally the protocol and other documentation may identify SAEs that do 
not need immediate reporting and SAEs falling under these categories should be 
recorded and reported according to the protocol. Where GSTT is the Sponsor and an 
SAE occurs that does not require immediate reporting, this SAE should be reported in the 
Annual Progress Report and copied to R&D. All adverse events that are to be reported to 
R&D Directorate must be signed and dated and completed by the Investigator. 
 
 
 
6. Definition of the End of Trial 
 
 
The end of trial is after the end of visit five (twenty forth month follow-up). Following 
that, patients will be reviewed normally either at their GDP or at Guy's Hospital. 
7. Direct Access to Source Data and Documents 
The investigators and KCL will permit trial-related monitoring, audits, REC review, and 
regulatory inspections (where appropriate) by providing direct access to source data and 
other documents such as patients’ case sheets and notes.  
8. Ethics & Regulatory Approvals 
The study will be conducted in compliance with the principles of the Declaration of 
Helsinki and the principles of GCP. Any subsequent protocol amendments will be 
submitted to the REC, and the REC will be provided with progress reports, and a copy of 
the Final Study Report. 
 

 
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9. Quality Assurance, Data Handling, Publication Policy and Finance 
 
Patients will be allocated a unique identification number. The Principal Investigator will 
maintain a database of the patient's personal data, clinical notes and treatment records. 
This will be stored in the office of the Chief Investigator Prof Francesco Mannocci in 
Room 309, Floor 25, Tower Wing, Guy’s Hospital. Only the chief investigator and 
researchers will have access to the participants' personal data during the study. The 
personal data will be stored for 6 months and the research data for 3 years after the study 
has ended. The trial will be registered on the GSTFT NHS R&D database and a public 
database: clinicaltrials.gov. The results of the study will be published in peer reviewed 
scientific journals, internal reports and in conference presentations. The study is self-
funded.  
 
 
 
 
 
 
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