Clinical Investigation of the F-Composite 2 System in Direct Filling Therapy
Phase: NA
Conditions: Dental Caries, Unsatisfactory or Defective Restoration of Tooth
Sponsor: Ivoclar Vivadent AG

 
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Clinical Investigation Protocol  
(incl. statistical considerations) 
 
 
Clinical examination of the 
F-Composite 2 Systems 
in the direct filling therapy 
 
(NCT03221660) 
 
 
 
 
 
 
 
 
 
 
 

 
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INDEX 
 
 
1. 
OBJECTIVES AND HYPOTHESES OF THE CLINICAL INVESTIGATION ................................ 3 
2. 
GENERAL OVERVIEW OF THE CLINICAL INVESTIGATION .................................................... 4 
3. 
JUSTIFICATION FOR THE STRUCTURE OF THE CLINICAL INVESTIGATION .................... 4 
4. 
INVESTIGATORS .................................................................................................................................... 5 
5. 
MATERIALS ............................................................................................................................................. 5 
6. 
RISKS AND BENEFITS OF THE INVESTIGATIONAL PRODUCT AND THE CLINICAL 
INVESTIGATION ................................................................................................................................................ 6 
7. 
STRUCTURE OF THE CLINICAL INVESTIGATION ....................................................................... 7 
7.1 GENERAL INFORMATION ............................................................................................................ 7 
7.2 PRODUCTS AND REFERENCE PRODUCTS .................................................................................... 8 
7.3 PARTICIPANTS (IN-/EXCLUSION CRITERIA) .................................................................................. 9 
7.4 TREATMENTS ......................................................................................................................... 10 
7.5 SPECIFICATIONS FOR MONITORING .......................................................................................... 11 
8. 
STATISTICAL CONSIDERATIONS ................................................................................................... 12 
9. 
DATA MANAGEMENT ......................................................................................................................... 12 
10. 
CHANGES TO THE CLINICAL INVESTIGATION PROTOCOL ................................................. 13 
11. 
DEVIATIONS FROM THE CLINICAL INVESTIGATION PROTOCOL ...................................... 13 
12. 
PROOF OF USE OF THE PRODUCT .................................................................................................. 13 
13. 
DECLARATION OF CONFORMITY .................................................................................................. 13 
14. 
PROCEDURE FOR OBTAINING CONSENT .................................................................................... 14 
15. 
ADVERSE EVENTS, ADVERSE EFFECTS OF THE PRODUCT AND PRODUCT DEFECTS.. 14 
16. 
POPULATION THAT CAN BE PRESSURED .................................................................................... 14 
17. 
PREMATURE TERMINATION OR SUSPENSION OF THE EXAMINATION ............................ 15 
18. 
PUBLICATION POLICY ....................................................................................................................... 15 
19. 
REFERENCES ........................................................................................................................................ 15 
 
 
 

 
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1. Objectives and hypotheses of the clinical investigation 
a) The aim of this prospective study is to evaluate the clinical performance of F-Composite 2, 
a proven flowable bulk material and adhesive system for the restoration of masticatory poste-
rior fillings (Class I and II), all three materials being polymerized with Bluephase PowerCure 
(flash mode).  
 
b) Primary hypotheses to be accepted or rejected by statistical data from the clinical investiga-
tion.  
 
Prof. Dr. Valentin Rousson from the Biostatistical Department of the Institute of Social and 
Preventive Medicine at the University of Lausanne, Switzerland, has performed a case number 
calculation. Assuming that a maximum of 10% post-operative hypersensitivity is acceptable, 
but actually only 5% is expected, the following formula can be used to calculate the case num-
ber (80% power, using a chi-square test at 5% probability of error)  
N = (1.96*sqrt(0.95*0.05)+0.84*sqrt(1*0))^2/(1-0.95)^2 = 73 participants or fillings 
 
Furthermore, if one assumes - based on internal experience - that after one year there is a 
drop-out rate of 2%, 75 fillings are necessary at the beginning of the study to statistically con-
firm the primary endpoint (post-operative hypersensitivities). 
  
(c) claimed and intended performance of the test product, which shall be demonstrated. 
The following working hypotheses should be clarified: 
• 
Teeth restored with the F-Composite 2 system have postoperative hypersensitivity in a 
maximum of 10% of cases after 1 month.  
• 
A maximum of one tooth shows a loss of vitality within 12 months. 
• 
With the selected application protocol, the F-Composite 2 system enables a filling qual-
ity at least comparable to F-Composite (see study "Clinical investigation of Flash Com-
posite in direct restorative therapy" CEC-ZH No. 2011-0150/5.) After 2 years a maxi-
mum of 3 fillings should be replaced due to poor quality. 
 
(d) The following risks shall be assessed: 
- post-op discomfort. In almost all clinical studies with direct filling materials, postoperative 
hypersensitivity occurs in the range of a few percent of the treated teeth. Whether the proba-
bility of occurrence is increased when using the F-Composite 2 restorative system can only be 
estimated by a clinical study. 
- Inflammation/death of the pulp (the "dental nerve"). In December 2015 a clinical study was 
completed after an observation period of three years (KEK-ZH No. 2011-0150/5), in which the 
filling material was polymerized with 10 000 mW/cm2 for one second, but without exposing the 
adhesive to this light intensity. No permanent damage to the pulp due to the high light intensity 
or temperature gradient was observed. In addition, Bluephase PowerCure was used to inves-
tigate the temperature gradient in the pulp in in vitro studies on extracted teeth. The absolute 
temperature was comparable to other lamps (recorded in investigator's brochure). However, 
the temperature gradient was steeper. 
- Cracks in the tooth structure or between tooth and restoration or marginal gaps which could 
lead to discoloration, secondary caries, filling fracture, filling loss or tooth fracture. In very se-
verely hollowed cavities on extracted molar teeth with undercuts (worst-case scenario) under 
the cusps, horizontal cracks in the tooth structure could be observed in vitro in bulk fillings with 
the flowable composite (recorded in validation report examiner brochure). For this reason, spe-
cial attention is also paid to this point during the clinical investigation.   
- Unexpected changes in the filling surface that could lead to roughness, discoloration or in-
creased wear of the material.  As the material is similarly polishable as a conventional compo-
site material, it is expected that no more surface discolouration will be observed. 
 

 
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2. General overview of the clinical investigation 
The F-Composite 2 system is a coordinated system of filling materials, adhesive and polymer-
ization unit for direct restorative therapy in dentistry. 
The aim of this single-arm prospective clinical study is to investigate the F-Composite 2 system 
in direct filling therapy of class I and II cavities. 
 
The following working hypotheses should be clarified: 
 
• 
Teeth restored with the F-Composite 2 system have postoperative hypersensitivity in a 
maximum of 10% of cases after 1 month, which corresponds to a frequency as de-
scribed in the literature.   
• 
With the selected application protocol, the F-Composite 2 system enables at least com-
parable restorative quality to F-Composite (see study "Clinical investigation of Flash 
Composite in direct restorative therapy" CEC-ZH No. 2011-0150/5.) After 2 years a 
maximum of 3 fillings should be replaced due to poor quality.  
• 
The rate of loss of vitality after 1 year is maximum 1%, which corresponds to a fre-
quency as described in the literature.  
 
The clinical investigation will be conducted with a maximum of 75 patients. No more than two 
restorations will be placed in any one patient. For inclusion and exclusion criteria, see item "7.3 
Participants". 
 
Recalls take place after 6, 12, 24, 60 months. 
 
Aftercare 
At the end of the study period or when patients leave the study, they will continue to be routinely 
cared for by their private dentist.  
 
3. Justification for the structure of the clinical investigation 
In summary, it can be concluded from the literature cited in the investigator's brochure that 
restorative composites are suitable for the intended indications and show a clinically accepta-
ble performance. 
 
Up to now, polymerization of the adhesive or a composite increment takes 5 to 40 seconds, 
depending on the material used and the polymerization lamp used to cure the material. Cur-
rently, the upper limit of available light intensities for direct restorations is approximately 2'000 
mW/cm2. In a recent study from Norway (Kopperud et. al, 2017), in which 740 dentists from 
the public sector were interviewed, it was shown that these dentists exposed each composite 
increment for an average of 27 s.  
In the experimental fillingsystem F-Composite 2, the components are cured with the new 
Bluephase PowerCure polymerization light. In the special flash mode, the Bluephase Power-
Cure emits blue light with an intensity that is 1.7 times higher than that of the Bluephase Style 
20i, the most powerful light unit from Ivoclar Vivadent AG to date. The Bluephase PowerCure 
polymerization light emits 3000 mW/cm2 and thus allows the materials to be cured in 3 seconds 
in combination with F-Composite 2, a flowable composite and Adhese Universal. 
 
As the laboratory tests and technical data of the F-Composite 2 system have shown promising 
results (recorded in investigator's brochure), clinical results are now to be collected. The main 
focus is on the frequency of occurrence of postoperative hypersensitivities, the investigation 
of edge quality and surface behaviour. 
 

 
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The fillings are examined and evaluated after certain times (recalls) according to defined cri-
teria. The clinical performance and the clinical success of the restorative material are meas-
ured. 
 
4. Investigators 
The principal investigator is Dr. Lukas Enggist. Dr. Enggist and the other investigation-site 
team members will place resp. evaluate the restorations. An investigator-blinding is carried out 
during the evaluation of the fillings during recall: the examiner does not know who placed the 
fillings. All follow-up examinations and the baseline findings are performed by an experienced 
evaluator. (stated in 7.1 (b)) 
 
5. Materials 
a) F-Composite 2 and the flowable composite are light-curing composite materials for direct 
restorative therapy in dentistry. Adhese Universal is a universal adhesive which ensures the 
adhesion of composites to enamel and dentin. It is indicated for direct and indirect restorative 
therapy. According to the EC Directive on Medical Devices 93/42/EEC, Annex IX, Rule 8, 1st 
indent, it is a Class IIa medical device. The flowable composite and Adhese Universal have 
already been on the market for some time and have proven their worth. What is new here is 
the polymerization in only three seconds. F-Composite 2, on the other hand, is a newly devel-
oped material that does not yet bear the CE mark.  
Bluephase PowerCure is a polymerization light which emits blue light in higher intensity than 
the most powerful light unit Bluephase Style 20i from Ivoclar Vivadent AG (2000 mW/cm2 in 
turbo mode). The Bluephase PowerCure polymerization light emits 3000 mW/cm2 . It is also a 
Class IIa medical product, which is not yet CE certified.  
 
F-Composite 2, the flowable composite, Adhese Universal and Bluephase PowerCure are a 
coordinated system consisting of composite restoratives and adhesive system as well as an 
LED polymerization unit that allows composite layers up to 4 mm thick to be cured in only 3 
seconds for posterior restorations.  
 
Details of the composites and the adhesive 
- 
Composition 
- 
Indication 
- 
Contraindication 
- 
Side effects 
- 
Interactions 
as prepared in the provisional Instructions for Use for clinical investigation of F-Composite 2, 
a flowable composite and Adhese Universal. 
 
Details of the polymerization lamp  
- 
Product overview 
- 
Security 
- 
Commissioning 
- 
Operation 
- 
Maintenance and cleaning 
- 
Product specification 
as prepared in the provisional Instructions for Use for clinical investigations of Bluephase 
PowerCure 
 
b) The four products (F-Composite 2, a flowable composite, Adhese Universal and Bluephase 
PowerCure) are manufactured by the dental company Ivoclar Vivadent AG, Bendererstrasse 
2, 9494 Schaan, Liechtenstein. 
 
c) The batch numbers of the materials used and of the lighting unit can are recorded in CRF I.  

 
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d) Traceability during and after testing is ensured by batch numbers (filling materials) and serial 
numbers (equipment). 
 
e) Intended purpose in the planned clinical investigation:  
The restorative materials F-Composite 2 and the flowable composite are intended for direct 
restorative therapy in the posterior region (Class I and II cavities). The Bluephase PowerCure 
polymerization light is designed for high-energy bulk curing of the F-Composite 2 material, the 
flowable composite and Adhese Universal when used in Class I and II cavities. 
f) populations and indications for which the test product is intended: 
Any person between 18 and 65 years of age, who is eligible for the indication "Class I or II 
posterior filling", can be treated. The gender distribution should be 40-60% women and 40-
60% men (see also point 7.3). 
g) The test products F-Composite 2 and the flowable composite are composites which consist 
mainly of inorganic fillers and monomers. In addition, they contain additives, initiators, stabi-
lizers and pigments. Details on the composition can be found in the Instructions for Use for F-
Composite 2 and the flowable composite. When used as directed, the material comes into 
contact with tooth structure, i.e. with dentin and enamel. Dentin and enamel are pretreated 
with the established bonding agent (Adhese Universal). The products F-Composite 2 and the 
flowable composite do not contain any human or animal substances or derivatives and also no 
biologically active substances. 
h) General dental training is sufficient for the application of the F-Composite 2 system. Within 
the framework of this training, the placement of fillings with a composite is state of the art 
nowadays. The handling of the Bluephase PoweCure polymerization light is trained in the 
course of monitoring on the basis of the provisional Instructions for Use. 
i) there are no specific medical or surgical procedures associated with the use of the test device 
 
6. Risks and benefits of the investigational product and the clini-
cal investigation 
a) Participation in this clinical investigation could have the following benefits: The F-Composite 
2 system allows a shorter treatment time. On the one hand, the risk of unintentional slippage 
of the light guide on the filling during the reduced exposure time could be reduced, which would 
contribute to the safe curing of the composite. On the other hand, it could be easier for the 
practitioner to keep the surgical field dry during the reduced exposure time of the composite. 
Both factors could increase the process reliability and thus the quality of composite fillings. 
These benefits must be weighed against the risks mentioned below.  
It is also essential that the treatment and all follow-up examinations are free of charge and that 
the study recalls ensure regular monitoring of the general dental findings.  
 
b) No foreseeable adverse effect(s) of the product are known. 
 
c) Risks associated with the test product itself are listed in the Instructions for Use F-Composite 
2, the flowable composite and Adhese Universal under the heading 'Side effects' and under 
the heading 'Warning'. All risks also exist when conventional products are used in direct re-
storative therapy. Due to the high light intensity of the polymerization unit, the gradient of tem-
perature changes in the pulp is increased. It is possible that the patient may feel this if no local 
anaesthesia is applied. The patient decides whether the procedure is performed under anaes-
thesia or not. According to in vitro experiments, the maximum temperature reached in the pulp 
is comparable to conventional polymerization devices. If the energy input is too high, the pulp 
could suffer thermal damage. Therefore, within 30 s, the Bluephase PowerCure can only be 
exposed twice in a row for 3 seconds each time. This lock can be manually unlocked by the 
dentist if the clinical situation requires it. Thermal damage to the soft tissue can be ruled out in 
Class I and II when used as intended, since the distance between the optical fibre and the 
tissue is sufficient in these situations. The polymerization of cervical fillings is not indicated. 

 
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No in vitro examination can serve to conclusively assess the risk of postoperative hypersensi-
tivity. Therefore this study must be carried out.  
 
d) There are no risks in connection with participation in the clinical investigation other than 
those mentioned under a)-c). 
 
e) Possible interactions with concomitant medical treatments are not expected. 
 
f) If the Instructions for Use for F-Composite 2, the flowable composite, Adhese Universal and 
for Bluephase PowerCure are followed, there are no further measures to be taken to control 
or mitigate the risks. 
 
g) risk/benefit justification. 
The F-Composite 2 system is a novel material or technology with which no clinical experience 
is yet available. Despite thorough laboratory tests, undesirable effects cannot be excluded. For 
example, post-operative discomfort or inflammation or the death of the pulp (the "tooth nerve") 
could occur, or cracks could appear in the tooth structure or between the tooth and the resto-
ration, or marginal gaps could occur which could lead to discoloration, secondary caries, filling 
fracture, filling loss or tooth fracture. 
Unexpected changes in the filling surface could result in roughness, discoloration or increased 
wear of the material. 
Components of the restorative materials used or the adhesive could cause sensitization and 
allergies (information is contained in the corresponding instructions for use). 
The high light energy of the Bluephase PowerCure could cause overheating or burning of the 
irradiated tissue, resulting in damage to the pulp, the periodontium or the gums. 
Flash Composite 2 has been thoroughly tested for possible toxicological and mutagenic prop-
erties. Based on the available knowledge, there is no risk to the patient for reasons of toxicol-
ogy and mutagenicity. 
 
 
7. Structure of the clinical investigation 
7.1 General information 
a) It is a single-arm clinical investigation without a control or comparison group. This design 
was chosen because clinical studies ("Clinical investigation of Flash Composite in direct re-
storative therapy" CEC-ZH No. 2011-0150/5; "Clinical investigation of AdheSE One F Upgrade 
in direct restorative therapy" CEC-ZH_NR. 2012-0076) with direct fillings have already been 
conducted by the same dentists in the same institution. Accordingly, existing data regarding 
the quality of fillings can be used for comparison purposes. The chosen study design allows 
higher case numbers, which seems reasonable in view of the primary endpoint.  
 
b) An investigator-blinding is carried out during the evaluation of the fillings during recall: the 
examiner does not know who placed the fillings. All follow-up examinations and the baseline 
findings are performed by an experienced evaluator. 
 
c) Primary endpoint: postoperative hypersensitivity 
 
Secondary end points: devitalization and therefore necessary endodontic treatment, quality of 
filling and therefore necessary replacement of fillings  
 
d) The following assessment criteria shall apply: 
 
Baseline Findings 
The participants are recalled 7-10 days after placing the filling to record the baseline findings. 
In addition to the clinical examination, the participants are also questioned regarding sensitivity 

 
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to temperature and occlusion. The aesthetic integration of the filling is evaluated, the occlusion 
is checked and corrected if necessary. Photos of the restoration are also taken. For the base-
line findings and for all recalls, the restorations are examined and evaluated (SQUACE and 
FDI criteria) using a special evaluation sheet. 
On the findings sheet, the patient has to draw the sensitivity of the tooth in everyday life re-
garding temperature and bite sensitivity on an unscaled straight line of 10 cm. The distance 
from the left edge (zero point = no discomfort or pain) is measured to within 1 mm in the eval-
uation.  
In the semi-quantitative evaluation of the fillings (SQUACE=SemiQUantitative Clinical Evalua-
tion), the following findings are documented: secondary caries FDI 12, marginal gap FDI 6.b, 
marginal deficits FDI 6.c, marginal discoloration FDI 2.b and marginal fracture FDI 6.a (in each 
case as a percentage of the total margin) 
The following FDI criteria are assessed using the FDI rating system 
• 
Postoperative hypersensitivity or tooth vitality FDI 11 
• 
Surface gloss FDI 1 
• 
Surface discoloration FDI 2a 
• 
Colour match and translucency FDI 3 
• 
Fracture of material and filling retention FDI 5 
• 
Proximal contact point FDI 8 
• 
Patient satisfaction FDI 10 
• 
Tooth integrity (tooth cracks and fractures) FDI 13 
 
Based on the FDI System for Clinical Evaluation of Restorations (Hickel et al 2007, 2010), 
evaluations are assigned for each FDI criterion according to the following scheme  
1= clinically ideal 
2= clinically good 
3= clinically acceptable 
4= no longer clinically acceptable (but repairable) 
5= clinically unacceptable, restoration must be replaced (repair not possible or not practical) 
 
Horizontal cracks are plotted on the printout of oral or vestibular photographs of the tooth (be-
fore and after the filling is placed or during recall) and compared with the preoperative findings.  
 
Follow-up examinations 
Recalls take place after 6, 12, 24, 60 months. The restorations are evaluated according to the 
above criteria.  
Photos are taken of all restorations at the examination appointments. If a patient suffers from 
postoperative complaints, the patient is examined again 14-20 or 30-35 days after the filling 
has been placed.  
 
e) No special test equipment is used for the assessment of the test variables. 
 
f) instructions for the exchange of participants are not required and no exchange takes place 
 
7.2 Products and reference products 
The following materials are used in the clinical study:  
conditioning agents: 
Total Etch - Gel for enamel etching and dentine conditioning for direct filling therapy with com-
posites 
 
Adhesive system: Adhese Universal - Bonding agent between dentin or enamel and composite 
 

 
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Composite restoratives: 
- Test product: The flowable composite - light-curing flowable bulk composite filling material 
as first increment (maximum 4 mm). 
- Test product: F-Composite 2- light-curing modellable composite filling material as obligatory 
covering layer of at least 1 mm 
 
Polymerization lamp:  
- Bluephase PowerCure with flash mode for polymerization of the adhesive and the composites 
in 3 s each.  
 
The conditioning agent, the adhesive and the flowable composite have already been intro-
duced to the market and have proven to be clinically effective.  
 
7.3 Participants (In-/Exclusion criteria) 
a) inclusion criteria for the selection of participants 
• 
Age: 18-65 years 
• 
40-60% women, 40-60% men 
• 
Indication for a direct filling of class I or II in permanent premolars or permanent molars 
o Replacement of insufficient fillings (e.g. due to marginal caries, fracture of the 
filling, poor surface quality, poor aesthetics, unwanted filling material, leaky 
margin, marginal gap, etc.) 
o extensive primary caries 
• 
Vital tooth (cold test) 
• 
Single-, double- or triple-surface fillings in the posterior region, where a maximum of 25% 
should be single-surface fillings (class I) with antagonists. 
• 
The occlusally assessed area of the filling must be at least 1/3 of the total area of the tooth. 
This criterion is estimated.   
• 
Participant wishes to receive care within the scope of the study (written declaration of 
consent after detailed explanation and study of the patient information). 
• 
Maximum 2 restorations per patient. 
• 
Preoperative complaints on the tooth to be restored (maximum 3 on visual analogue scale 
(0= no complaints, 10= maximum possible pain) due to temperature stimulus or sensitivity 
to bite 
• 
Sufficient German language skills 
 
b) exclusion criteria for the selection of the participant. 
• 
Not completed hygiene phase or poor oral hygiene 
• 
Sufficient drainage of the surgical field not possible 
• 
Patients with a proven allergy to one of the ingredients of the materials used  
• 
Patient is allergic to ingredients of the local anaesthetic Ultracain DS (active ingredient: 
articaine; vasoconstrictor), if anaesthesia is desired 
• 
Patients with severe systemic diseases 
• 
Devital or pulpit teeth 
• 
Periodontally insufficient dentition 
• 
Restorations with cusp abutments 
• 
open lateral bite 
• 
missing antagonist 
• 
Indication for direct capping 
• 
Pregnancy (women of child-bearing age receive a free pregnancy test for self-testing in 
advance, the negative result of which they document with their declaration of consent) 
 

 
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c) Patients discontinue the study on their own initiative or withdraw for reasons that make 
further assessment of the filling impossible. These include, for example, extraction of the tooth 
due to a cause independent of the study, the change in the opposing dentition or treatment by 
an external dentist. 
These patients are considered to be drop-out and are reported separately with the drop-out 
cause (CRF V). The recall data obtained up to the time of drop-out are used in the analysis. 
 
 
d) the date of recording. 
After a positive ethics vote and registration at "clinicaltrials.gov", the study will start, i.e. this 
marks the earliest point of admission. 
 
e) Expected total duration of the clinical investigation. 
The expected total duration of the clinical investigation is 5 years and 4 months. 
f) The expected duration of participation of each participant in the treatment scheme in Table 
1 is 5 years (60 months). 
 
g) The required number of participants to be included in the clinical investigation shall not 
exceed 75. 
 
h) The estimated time needed to obtain this number of participants (i.e. recording time) 
is estimated at 4 months. 
 
7.4 Treatments 
a) Description of all treatments administered to the investigation participants during the clinical 
investigation Three operators place 25 fillings each. 
 
Preparatory measures and cavity preparation 
• A medical and dental anamnesis and detailed findings are taken for each patient and, 
if necessary, x-rays are taken. A visual analogue scale is used to record the preoper-
ative complaints of the tooth to be restored with regard to temperature stimulus and 
bite sensitivity. However, no cold or bite sensation is set for this purpose. The vitality 
is checked with a cold spray. In addition, a therapy plan is drawn up in accordance 
with the restoration concept. 
• A digital photo of the initial state is taken. The vestibular and oral views are printed 
out. The occurrence and extent of horizontal tears are drawn on it.  
• If possible, rubber dams are used for drainage. If a rubber dam is not possible, an 
appropriate relative draining method is used (OptraGate, cotton rolls, saliva ejector). 
• Then the insufficient filling or caries is removed. 
• The preparations are done with 80 μm diamonds, a finish of the cavity edges with 25 
μm diamonds. The cavity edges in the enamel are chamfered, but not gingivocervi-
cally. 
 
Measurement of the cavity and renewed documentation of melt cracks 
• A digital photo of the prepared cavity is taken 
• The lowest point of the respective proximal boxes and occlusal pull-through is meas-
ured with a PA probe (Hu-Friedy PCPUNC 15) and documented on the CRF I. The 
reference for the proximal box is the proximal-occlusal cavity margin in the marginal 
ridge area and, for determining the occlusal pull-through depth, the occlusal cavity 
margin adjacent to the lowest point. The determination should be made with an accu-
racy of ±1 mm. 
• The average width of the cavity is given in absolute terms (accuracy ±1mm). The 
already mentioned periodontal probe is also used as an aid here. 

 
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• Prior to conditioning, the tooth is again examined for horizontal enamel cracks, which 
are recorded in the printed photographs in terms of their extent and localization and 
recorded on the CRF I. A cold-light fibre optic (light probe by Lercher) is used as an 
aid. 
• The residual dentin thickness above the pulp is determined with a prepometer at the 
site with the lowest layer thickness (Wegehaupt et al. (2009)).  
 
The partial matrix system from Garrison (Compositight) or Triodent (V3) is used as the 
matrix. 
 
Application of the etching gel and adhesive system 
• According to GI in Etch&Rinse mode, exposure time of Total Etch in enamel 30 s, 
dentin 10-15 s. The adhesive must be rubbed in for 20 s.  
• The adhesive is cured with the Bluephase PowerCure in flash mode for 3 s. 
 
Application of the composite in the bulk fill technique 
• Application of the flowable composite in a horizontal layer of maximum 4 mm, taking 
into account the minimum layer thickness of the top layer.  
• Application of F-Composite 2 in layers of max. 4 mm. To simplify the design of the 
anatomy, several oblique increments are permitted as cover layer. The minimum layer 
thickness of the top layer is 1 mm.   
• Light polymerization per layer for 3 s with Bluephase PowerCure (flash mode, 3000 
mW/cm2) 
• Finishing of the filling with composite shape diamonds and final polishing with the one-
step polishing system OptraPol (Ivoclar Vivadent) 
 
 
b) Apart from monitoring, there are no other activities carried out by representatives of the 
sponsor (IvoclarVivadent AG). 
c) A distortion of the results could arise from the following factors: 
- 
Mainly older patients (> 45 years) are included in the study. Older patients are 
less prone to post-operative hypersensitivity than younger patients due to pulp 
retraction caused by secondary dentin. 
- 
The replacement of insufficient fillings or the treatment of primary carious le-
sions results in shallow cavities with a residual dentine thickness of 1.5-3 mm. 
A greater residual dentin thickness may reduce the risk of pulp irritation caused 
by the high light intensity of the polymerization light and thus the number of 
postoperative hypersensitivities. Small to medium-sized cavities also reduce 
the risk of horizontal enamel cracks. 
- 
Due to the explanatory talk of the participants or the knowledge of the operators, 
both participants and operators could be sensitized regarding the important clin-
ical parameter "post-operative hypersensitivity" and thus falsify the result. 
 
 
If material-dependent problems occur that require replacement of the F-Composite 2 fillings, a 
replacement filling made of established standard materials is placed free of charge. No further 
medical care is planned after the test. 
 
7.5 Specifications for monitoring 
 
This clinical investigation will be monitored by the sponsor at defined timely intervals. The 
Monitoring Plan lists the activities within the scope of monitoring. 
 
 

 
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8. Statistical considerations 
a) Due to the study design, no special statistical methods are necessary. 
b) The sample size is 75 fillings 
 
c) validity of the clinical investigation: the system is suitable for the market if the acceptance 
criteria are met. 
 
d) Expected drop-out rate: Analysis of older comparable studies show that an annual drop-out 
rate of 2% can be expected. Accordingly, three fillings could no longer be checked after 2 
years.  
 
e) Acceptance criterion for post-operative hypersensitivity after 4 weeks: ≤ 10% (=6 fillings). 
Acceptance criterion for loss of vitality after 1 year: maximum 1 restored tooth 
Acceptance criterion for filling replacement after 2 years: maximum 3 fillings 
 
g) If more than 50% of the patients suffer from postoperative hypersensitivity after placing at 
least 20 fillings, the study would be terminated.  
 
k) If patients discontinue the study or drop out for other reasons (including extraction of the 
tooth from a cause not related to the study, change of the opposing dentition or treatment by 
an external dentist), they are considered a drop-out and are reported separately with the drop-
out cause (CRF V).  
The recall data obtained up to the time of withdrawal from the study are used in the evaluation. 
 
 
9. Data management 
a) Data verification is carried out with plausibility checks. The data is encrypted, since the 
patient names do not appear in the data tables, but the cases can be assigned using case 
numbers and patient IDs.  
 
c) The archiving of the data takes place on the company's secure servers. The data is stored 
as SPSS data sheets in anonymized form. The traceability is given by case numbers.  
 
d) The retention period of the data after completion of the study is 10 years. 
 
Since all persons involved in the study, especially the operators and the evaluator, are familiar 
with and apply the company's internal guidelines regarding "Good Documentation Practice" 
(SOP-00081-EN; Good Documentation Practice), the traceability of changes is ensured by the 
dating and sizing of corrections.  
 
CRFs, radiographs and clinical images will be collected as source data in this study. 
 
Authorities and the Monitor will be granted access to the original data at any time, should this 
be necessary.  
 
If a participant withdraws his or her consent, the health-related personal data will be made 
anonymous after the data evaluation is completed. Despite revocation, the participant will be 
offered follow-up treatments to the extent required to protect his or her health.  
 
 

 
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10. 
Changes to the clinical investigation protocol 
Substantial changes to the approved clinical investigation must be approved by the Ethics 
Committee prior to their implementation. Excepted from this obligation are measures that must 
be taken immediately to protect the participating persons. 
The following are considered to be significant changes: 
• 
Changes that affect the health and safety of the participating persons or their rights and 
obligations 
• 
changes in the study plan, in particular changes due to new scientific evidence con-
cerning the test design, test method, objective criteria or statistical design; 
• 
the change of the place of execution or the execution of the clinical investigation at an 
additional place of execution; 
the change of sponsor, coordinating investigator or investigator-in-charge at a site. 
All other changes are submitted to the Ethics Committee once a year together with the safety 
report.  
 
Substantial changes to the approved clinical investigation must be approved by the Liechten-
stein Office of Public Health before they are implemented. This obligation does not apply to 
measures that must be taken immediately to protect the participating persons. 
In this context, significant changes are considered to be substantial: 
• 
Changes to the medicinal product or its administration or use; 
• 
Changes due to new preclinical and clinical data that may affect product safety;  
• 
Changes concerning the manufacture of the medicinal product which may affect prod-
uct safety. 
Other changes concerning documents submitted to the Office of Public Health must be notified 
to the Office of Public Health as soon as possible. 
 
 
11. 
Deviations from the clinical investigation protocol 
The investigator is not permitted to deviate from the CIP, except under emergency conditions 
to protect the rights, safety and health of the participant. If safety and protective measures 
must be taken immediately during the conduct of the clinical investigation, the investigator must 
notify the Ethics Committee within two days of these measures and of the circumstances which 
made them necessary. 
In such a case, the sponsor must also submit a report to the Office of Public Health. 
 
 
12. 
Proof of use of the product 
The proof of use of the test product shall be documented as described in 6.9 of EN ISO 
14155:2011. 
 
 
13. 
Declaration of conformity 
All groups involved in the investigation, as well as their individual members, undertake at all 
times during the investigation to 
 the Declaration of the World Medical Association of Helsinki, 
 local legislation 
 the EN ISO 14155:2011 
 the clinical investigation plan to be observed. 
 
The investigation may not begin before the approving opinions of the competent ethics com-
mittee and the supervisory authority have been received. 

 
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Possible additional requirements of the ethics committee or the supervisory authority must be 
observed. 
 
All patients participating in the clinical examination are insured against damages caused by 
the examination material. 
 
 
14. 
Procedure for obtaining consent 
The patients are informed orally and in writing about the course of the experiment, the materi-
als to be tested and any risks and sign a corresponding declaration of consent. Before the 
patient concerned decides on the consent, he/she is given a period of reflection of at the latest 
3 working days. Every patient has the right to refuse further participation in the study at any 
time.  
According to the patient information, the participant will be informed immediately if at any time 
during the conduct of the study aspects should arise that could influence the willingness of 
patients to participate in the study. 
 
 
15. 
Adverse events, adverse effects of the product and prod-
uct defects 
All incidents that are detrimental to the patient, whether or not they are caused by the object 
of investigation, are undesirable incidents. If these adverse events are due to the object of 
investigation, they are adverse effects. Each of these adverse reactions must be documented 
on the follow-up examination form (CRF IV). The clinical investigator must decide whether or 
not the adverse reactions could have been caused by the materials under investigation and 
thus whether or not an adverse effect exists.  
 
A serious adverse event (SAE = Serious Adverse Event), which cannot be ruled out as being 
attributable to the investigational product or to an intervention carried out in a clinical investi-
gation, is reported to the Cantonal Ethics Committee in Zurich within 7 days. In addition, a 
report must be made to the Liechtenstein Office of Public Health within 7 days ("Reporting form 
for clinical investigations with medical devices - Serious Adverse Event"). 
A serious adverse event in this study is an event that 
(a) resulted in death 
(b) resulted in a serious adverse health effect to the participant, which was either 
1) results in a life-threatening disease or injury, or 
2) results in a permanent impairment of a body structure or function, or 
3) results in hospitalisation or the extension of an existing hospital stay, or 
4) involves a medical or surgical procedure to prevent a life-threatening disease or injury or 
permanent impairment of a body structure or function 
Once a year, a safety report (ASR) is submitted to the Ethics Committee and the Office of 
Public Health, which contains a list of events (SEA) and establishes their causality for inter-
vention and assesses the safety of the participating patients 
 
If undesirable events occur that require treatment outside the practice, follow-up treatment is 
ensured by means of a detailed referral to the relevant specialist, family doctor or, if applicable, 
family dentist. 
  
 
16. 
Population that can be pressured 
During the planned clinical investigation, the investigational product will not be applied to pop-
ulations that can be put under pressure. 
 

 
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17. 
Premature termination or suspension of the examination 
The study can be terminated by the dentist, the sponsor or the manufacturer of the drugprouct. 
The following reasons can lead to this: 
• technical problems during the manufacturing process 
• Adverse events related to the testproduct that threaten the safety and health of the in-
vestigation participants (unacceptable risks) 
• lack of compliance (willingness to cooperate) of a patient 
Any interruption of the study must be reported to the Ethics Committee and the Office of Public 
Health within 15 days. An interruption or the regular end of the study must be reported to both 
institutions within 90 days. The final report must be submitted to the Ethics Committee and the 
Office of Public Health within one year of the end of the study.  
 
No study follow-up beyond the duration of the study is foreseen. 
 
 
18. 
Publication policy 
It is desirable that the principal investigator publishes the findings for scientific purposes. A 
manuscript should be provided to the sponsor for review at least 30 days prior to the planned 
publication. Suggestions for changes should only be considered if they do not compromise the 
scientific character or neutrality of the publication. Exceptionally, the client may request a post-
ponement of the publication up to a maximum of 90 days after submission of the manuscript if 
and to the extent that this is absolutely necessary to protect the client's intellectual property. If 
the client has not raised any objections within 30 days of receipt of the manuscript, the consent 
to publication is deemed to have been given. As this is an in-house study, conflicts of interest 
between the principal investigator and the sponsor are not to be expected. 
 
 
19. 
References 
 
Demarco FF, Correa MB, Cenci MS, Moraes RR, Opdam NJ (2012) Longevity of posterior 
 
composite restorations: not only a matter of materials  Dent Mater 28 87-101. 
 
Heintze SD, Rousson V (2012) Clinical effectiveness of direct Class II restorations - A 
 
meta-analysis  J Adhes Dent 14 407-431. 
 
Hickel, R., A. Peschke, et al. (2010). "FDI World Dental Federation: clinical criteria for the 
evaluation of direct and indirect restorations-update and clinical examples." Clin Oral 
Investig 14(4): 349-66. 
 
Hickel, R., J. F. Roulet, et al. (2007). "Recommendations for conducting controlled clinical 
studies of dental restorative materials. Science Committee Project 2/98--FDI World 
Dental Federation study design (Part I) and criteria for evaluation (Part II) of direct and 
indirect restorations including onlays and partial crowns." J Adhes Dent 9 Suppl 1: 121-
47. 
 
Kopperud S.E., et al., (2017) Light curing procedures – performance, knowledge level and 
 
safety awareness among dentists, Journal of Dentistry58: 67-73 
 
Manhart J, Chen H, Hamm G, Hickel R (2004) Buonocore Memorial Lecture. Review of the 
 
clinical survival of direct and indirect restorations in posterior teeth of the per
 
manent dentition Oper Dent 29 481-508. 
 

 
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Opdam NJ, van de Sande FH, Bronkhorst E, Cenci MS, Bottenberg P, Pallesen U, 
 
Gaengler P, Lindberg A, Huysmans MC, van Dijken JW (2014) Longevity of Pos terior 
 
Composite Restorations: A Systematic Review and Meta-analysis  J Dent Res 93 943-
 
949. 
 
Wegehaupt F, Betke H, Solloch N, Musch U, Wiegand A, Attin T (2009) Influence of cavity 
 
lining and remaining dentin thickness on the occurrence of postoperative hypersensi
 
tivity of composite restorations  J Adhes Dent 11 137-141.