Clinical Evaluation of a New Dual-cure Universal Adhesive for Indirect Restorative Treatment
Phase: NA
Conditions: Class I Dental Restorations, Class II Dental Restorations, Insufficient Dental Restoration, Caries, Dental
Sponsor: Ivoclar Vivadent AG

Clinical Study Protocol
Clinical evaluation of a new dual-cure universal adhesive for 
indirect restorative treatment 
Type of investigation: 
Clinical investigation concerning medical devices 
Categorisation: 
Category according to Art 6 ClinO-MD: C2 
Registration: 
Registry at ClinicalTrials.gov of the U.S. National Library of Medicine 
(http://www.clinicaltrials.gov) 
The trial gets registered in the supplementary federal database (Portal for 
clinical trials in Switzerland - SNCTP, https://www.kofam.ch/en/snctp-
portal/) upon its submission on BASEC.  
Furthermore, as soon as the new electronic system EUDAMED is 
operational, the clinical investigation will be retrospectively registered, if 
required. 
Study Identifier: 
OTCS187088487 (Document ID: OTCS187092274) 
Principal Investigator and 
Sponsor, or Sponsor-
Investigator: 
Principal Investigator (PI): 
Dr. med. dent. Lukas Enggist 
Internal Clinic of Ivoclar Vivadent AG 
Bendererstrasse 2 
9494 Schaan 
Fürstentum Liechtenstein 
Tel. 
  
Mail: 
 
Sponsor: 
Ivoclar Vivadent AG 
Patrizia Elkuch-Hoch 
Team Leader Study Management 
Bendererstrasse 2 
9494 Schaan 
Fürstentum Liechtenstein 
Tel.: 
 
Mail: 
 
Sponsor representative (if the 
Sponsor is not located in 
Switzerland) 
n.a.
Medical Device: 
 (Ivoclar Vivadent AG) 
CIP Version and Date: 
Version 4.0, 01.10.2024 
CONFIDENTIAL 
The information contained in this document is confidential and the property of the Ivoclar Vivadent AG. The 
information may not - in full or in part - be transmitted, reproduced, published, or disclosed to others than the 
applicable Competent Ethics Committee(s) and Regulatory Authority(ies) without prior written authorisation from 
the Sponsor except to the extent necessary to obtain informed consent from those who will participate in the 
investigation. 

Signature Page(s) 
10 number of the 
investigation: 
Title: 
OTCS187088487 Registry at ClinicalTrials.gov of the U.S. National 
Library of Medicine (http://www.clinicaltrials.gov) 
The trial additionally registers in the supplementary federal database 
(Portal 
for 
clinical 
trials 
in 
Switzerland 
SNCTP, 
https://www.kofam.ch/en/snctp-portal/) with its submission on BASEC. 
Furthermore, as soon as the new electronic system EUDAMED is 
operational, the clinical investigation will be retrospectively registered, if 
required. 
Clinical evaluation of a new dual-eure universal adhesive for indirect 
restorative treatment 
The Sponsor, the Principal lnvestigator have approved the CIP version 4.0 (01.10.2024) and confirm hereby to 
conduct the investigation according to the CIP, the current version of the World Medical Association Declaration of 
Helsinki, ISO14155 norm, ICH-GCP as far as applicable, and the local legally applicable requirements. 
Sponsor: 
Patrizia Elkuch-Hoch 
Place/Date 
Principal lnvestigator: 
Dr. med. dent. Lukas Enggist 
I 
Place/Da te 
OTCS 18709227 4 
Signature 
Signature 
Version 4.0, (01.10.2024) 
Page 2 of 17 

OTCS187092274 
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Page 3 of 17 
Table of Contents 
 
 
 
1.
 
 
 
 
 
2.
 
 
 
 
 
 
 
 
 
3.
 
 
 
 
 
 
 
3.4 
Safety Outcomes ......................................................................................................................... 12 
4.
CLINICAL INVESTIGATION DESIGN .......................................................................................... 13
4.1 
General clinical investigation design and justification of design ................................................. 13 
4.2 
Methods for minimising bias ........................................................................................................ 13 
4.2.1 Randomisation .................................................................................................................... 13 
4.2.2 Blinding procedures ............................................................................................................ 13 
4.2.3 Other methods for minimising bias ..................................................................................... 13 
4.3 
Unblinding Procedures (Code break) .......................................................................................... 13 
5.
CLINICAL INVESTIGATION INTERVENTION ............................................................................. 14
5.1 
Identity of the medical device under investigation ...................................................................... 14 
5.1.1 Experimental Intervention (medical device) ........................................................................ 14 
5.1.2 Control Intervention (standard/routine/comparator) ............................................................ 14 
6.
STATISTICAL METHODS ............................................................................................................. 15
6.1 Hypothesis ..................................................................................................................................... 15 
6.2 Determination of Sample Size ....................................................................................................... 15 
6.3 Statistical criteria of termination of the investigation ..................................................................... 15 
6.4 Planned Analyses .......................................................................................................................... 15 
6.4.1 Datasets to be analysed, analysis populations ..................................................................... 15 
6.4.2 Primary Analysis ................................................................................................................... 15 
6.4.3 Secondary Analyses ............................................................................................................. 15 
6.4.4 Interim analyses .................................................................................................................... 15 
6.4.5 Deviation(s) from the original statistical plan ........................................................................ 15 
6.5 Handling of missing data and drop-outs........................................................................................ 16 
7.
REFERENCES ............................................................................................................................... 17

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SYNOPSIS 
Sponsor 
Ivoclar Vivadent AG 
Title: 
Clinical evaluation of a new dual-cure universal adhesive for indirect restorative 
treatment 
Short title / 
Investigation ID: 
Clinical evaluation of a new dual-cure universal adhesive 
OTCS187088487 
Clinical Investigation 
Plan, version and 
date: 
CIP Version 4.0, 01.10.2024 
Registration: 
Registry 
at 
ClinicalTrials.gov 
of 
the 
U.S. 
National 
Library 
of 
Medicine 
(http://www.clinicaltrials.gov) 
The trial gets registered in the supplementary federal database (Portal for clinical trials 
in Switzerland - SNCTP, https://www.kofam.ch/en/snctp-portal/) upon its submission on 
BASEC.  
As soon as the new electronic system EUDAMED is operational, the clinical 
investigation will be retrospectively registered, if required. 
Category and its 
rationale: 
Category C2 (Art. 6 ClinO-MD)  
The medical device has no conformity marking. 
Name of the MD, 
Unique Device 
Identification (UDI), 
name of the 
manufacturer 
 in VivaPen + VivaPen DC (dual-curing) cannula 
UDI not available 
Manufacturer: 
Ivoclar Vivadent AG 
Bendererstrasse 2 
9494 Schaan 
Liechtenstein 
Stage of 
development: 
Pivotal stage  
The clinical investigation is conducted for a conformity assessment purpose. 
Background and 
rationale: 
The usage of a dental adhesive to lute ceramic inlays or onlays to teeth is necessary 
and state of the art to replace missing tooth structure. The investigational product 
 is a novel universal dual-cure adhesive. This clinical investigation is 
conducted to prove the clinical performance and safety of this new dental adhesive. 
Objective(s): 
The overall aim of this study is to evaluate the clinical performance and safety of the 
dental adhesive 
 for luting indirect ceramic restorations (inlays and onlays). 
The investigation seeks primarily to determine the rate of postoperative hypersensitivity 
occurrence after using 
 for the placement of indirect restorations. The 
secondary objective of this study is to assess the long-term clinical performance of 
 in terms of marginal quality, retention/fracture rate of the ceramic restorations, 
and vitality/fracture rate of the restored teeth. 
Outcome(s): 
The primary endpoint of this clinical trial is the incidence rate of postoperative 
hypersensitivity. The assessment of the postoperative hypersensitivity is performed 
and graded according to the FDI criteria (Hickel et al. 2007; Hickel et al. 2010, Hickel 
et al. 2022).  
The secondary outcomes are the vitality and fracture rate of restored teeth and the 
retention/fracture rate of restorations. These parameters provide information about the 
clinical performance of the bond of the restoration to the tooth structure. Another 
secondary outcome is the marginal quality of the restorations that also provides 
information about the quality of the bond between tooth structure and luting composite. 
The secondary outcomes will be assessed at all recalls with the respective FDI criteria 
(Hickel et al. 2022). 
Design: 
This is a prospective single-arm clinical investigation. The safety and performance 
results of 
 will be compared with the coded data of the control group (Adhese 
Universal) of an already performed clinical investigation ("Clinical evaluation of a new 
dual cure universal adhesive (Adhese Universal DC) in the indirect restorative therapy: 
A randomised, controlled clinical trial", NCT04475679). The study design of the 
planned clinical investigation follows the design of the previously conducted clinical 
investigation. The objectives, outcome parameters and methods are the same. 

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Inclusion / exclusion 
criteria: 
Inclusion criteria: 
- Age: 18-65 years
- Informed consent signed and understood by the subject
- Indication for indirect restorations (inlay, onlay) in molar or premolar - replacement of
insufficient fillings (e.g. due to caries at margins, filling fracture, fracture of the tooth,
poor quality of the surface, leaking margin, etc.) or extensive primary caries
- The occlusal area of the restoration must cover at least 1/3 of the occlusal area of the
tooth.
-Pre-operative discomfort of the tooth to be restored should not exceed 3 on the visual
analogue scale (VAS) (0=no pain, 10=maximum conceivable pain) due to temperature
stimulus or bite sensitivity
- Max. 2 restorations per participant in different quadrants.
- Vital tooth
- Healthy periodontium, no active periodontitis
- Contact with adjacent teeth (at least at one side) and opposing teeth present with at
least one contact point.
- Sufficient language skills
Exclusion criteria: 
- Sufficient isolation not possible, dry working field cannot be guaranteed
- Participants with a proven allergy to one of the ingredients of the materials used
(methacrylates, HEMA, potassium iodide, mequinol)
- Participants with proven allergy to local anaesthetics (Articain, sulfite)
- High caries activity/ poor oral hygiene
- Participants with severe systemic diseases
- Pregnancy
- Tooth with irreversible pulpitis
- Indication for direct pulp capping
- Part of the development project team of 
- Staff of the study management team
- Staff of the internal clinic
- Bleaching of teeth within the last 14 days
- Usage of peroxide-based disinfectants within the last 14 days
Measurements and 
procedures: 
After information and written informed consent the participants will receive a dental 
treatment in relation to the restorative indication (caries, tooth/restoration fracture, 
insufficient restoration, etc), which means that the inlay/onlay cavity will be prepared 
and a digital impression with an intraoral scanner (Trios 3Shape) will be taken. Then, 
the cavities will be temporarily restored with provisional restorations. The scans will be 
sent to the lab where dental technicians will provide the final restorations made of 
lithium disilicate e.max CAD. In the following appointment the final restorations will be 
luted and final corrections as well as the finishing and polishing procedures will be 
done.  
The baseline recall will take place 6-12 days after the insertion of the restoration.  At 
the baseline recall the study specific parameters will be evaluated according to the FDI 
criteria ranging from 1 excellent to 5 clinically not acceptable. 
Further recalls will be performed at 1, 6, 12, 24, 36 and 60 months after placement of 
the restoration. 
Intervention: 
After getting a tooth which is in a need of a restoration (inlay or onlay), the cavity will 
be prepared, and an optical impression is taken. Then provisional restoration is 
cemented during the time, which is necessary to produce the indirect restoration in the 
dental lab. This first treatment appointment takes around 2.5 h. In a second treatment 
appointment the indirect ceramic restoration is luted to the tooth surface by the 
investigational product 
 and the well-established luting composite Variolink 
Esthetic DC. This will take at maximum 2 hours. During the baseline appointment a 
repolish of the restoration can be done by the operator before the evaluator assesses 
the restoration and the tooth. This will take at maximum 30 minutes. All following recall 
visits will take no longer than 30 minutes.  
Control intervention 
(if applicable): 
n.a.
Number of subjects 
with rationale: 
45 teeth, at maximum two teeth per participant according to the statistical 
considerations. 
Duration of the 
investigation: 
5 years 

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Investigation 
schedule: 
October 2024 First- subject –In (planned) 
April 2031 of Last- subject –Out (planned) 
Investigator(s): 
-
Dr. Enggist Lukas, Bendererstrasse 2, 9494 Schaan
-
Dr. Carola-Sonia Pentelescu, Bendererstrasse 2, 9494 Schaan
-
Dr. Peschke Arnd, Bendererstrasse 2, 9494 Schaan
-
Dr. Hu Ming, Bendererstrasse 2, 9494 Schaan
-
Dr. Glebova Tatiana, Bendererstrasse 2, 9494 Schaan
-
Dr. Lydia Eberhard, Bendererstrasse 2, 9494 Schaan
-
Dr. Ronny Watzke, Bendererstrasse 2, 9494 Schaan
Investigational 
Site(s): 
This is a single center study. 
R&D Clinic 
Ivoclar Vivadent AG 
Bendererstrasse 2 
9494 Schaan 
Fürstentum Liechtenstein 
Statistical 
considerations: 
The trial is a continuation of the clinical trial "Clinical evaluation of a new dual cure 
universal adhesive (Adhese Universal DC) in the indirect restorative therapy: A 
randomised, controlled clinical trial (NCT04475679)". The methodology, the endpoints 
and the hypotheses are the same. The test product 
 is a further development 
of Adhese Universal DC. Therefore, the test group (
) will be compared to the 
control group (Adhese Universal) of the study mentioned above. In this clinical trial a 
dropout of 5 restorations is assumed. Therefore, the sample size is 45 instead of 40.  
Compliance 
statement: 
This investigation will be conducted in compliance with the CIP, the current version of 
the Declaration of Helsinki, ISO14155, ICH-GCP (as far as applicable) as well as all 
national legal and regulatory requirements. 

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ABBREVIATIONS 
AE 
Adverse Event  
ADE 
Adverse Device Effect 
ASADE 
Anticipated Serious Adverse Device Effect 
ASR 
Annual Safety Report 
CA 
Competent Authority  
CEC 
Competent Ethics Committee 
CIP 
Clinical investigation plan 
ClinO 
Ordinance on Clinical Trials in Human Research (in German KlinV, in French Oclin, in Italian 
OSRUm)
ClinO-MD 
Ordinance on Clinical Trials with Medical Devices (in German: KlinV-Mep, in French: Oclin-
Dim, in Italian: OSRUm-Dmed) 
CRF 
Case Report Form (pCRF paper CRF; eCRF electronic CRF) 
DD 
Device Deficiency 
DMC / DSMC 
Data Monitoring Committee, Data Safety Monitoring Committee 
FDI 
Fédération Dentaire Internationale 
Ho 
Null hypothesis 
H1 
Alternative hypothesis 
HRA 
Federal Act on Research involving Human Beings (in German: HFG, in French: LRH, in 
Italian: LRUm)
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH-GCP 
International Council for Harmonisation – guidelines of Good Clinical Practice 
IFU 
Instruction For Use 
ISF 
Investigator Site File 
ISO 
International Organisation for Standardisation 
ITT 
Intention to treat 
MedDO 
Medical Devices Ordinance (in German: MepV, in French: Odim, in Italian: Odmed)
MD 
Medical Device  
MDR 
Medical Device Regulation (EU) 2017/745 of 5 April 2017 
PI 
Principal Investigator 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SDV 
Source Data Verification  
SNCTP 
Swiss National Clinical Trials Portal 
SOP 
Standard Operating Procedure 
USADE 
Unanticipated Serious Adverse Device Effect 

OTCS187092274 
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INVESTIGATION SCHEDULE 
Study Periods 
Screening 
Treatment, Intervention 
Period 
Follow-up 
Visit 
1 
2 
3 
4***
5 
6 
7 
8 
9 
10 
11 
Time (hour, day, 
week) 
-17- (-45)
d
-14-
(-5) d
0 d 
Before 
visit 5 
6-12 d
1 m 
6 m 
12 m 
24 m 
36 m 
60 m 
Patient 
Information 
x 
Signed informed 
consent 
x 
Medical History 
x 
In- 
/Exclusion 
Criteria 
(x) 
x 
Tooth 
Examination 
x 
Pregnancy Test 
x 
Vitality test 
x 
x 
x 
x 
x 
x 
x 
x 
x 
VAS for tooth 
sensitivity 
x 
x 
x 
x 
x* 
x* 
x* 
x* 
Preparation 
of 
tooth, 
impression and 
cementation 
of 
provisional  
restoration 
x 
Try-in 
and 
cementation 
of 
final restoration 
x 
Use of 
 
x 
Excess removal, 
polishing, 
occlusion check 
x 
x 
Primary 
Variables 
x 
x 
x 
x 
x 
x 
x 
Secondary 
Variables 
x 
x** 
x 
x 
x 
x 
x 
Photographs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse events 
and 
device 
deficiencies 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
* only for participants who suffer from any kind of postoperative hypersensitivity
** Not all variables will be assessed (only dental hard tissue defects at restoration margin, patient’s view and fracture 
of material and retention) 
*** optional visit 
Page 8 of 17 

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1. BACKGROUND AND RATIONALE
1.1 Background and Rationale for the clinical investigation
1.2 Identification and description of the Investigational Medical Device
 is a dual-curing single-component dental adhesive for enamel and dentin that is compatible with all 
etching techniques (self-etch, selective-enamel-etch and etch & rinse techniques). The areas of application include 
adhesive cementation of indirect restorations and direct restorative procedures. More detailed information is 
provided within the Investigator's Brochure (IB) and the Instructions for Use (IFU). 
Caries is a chronic disease that is widely spread among the population all over the world affecting 60-90% of 
children and the vast majority of adults in industrialised countries (Pitts et al. 2017, Petersen et al. 2005). The 
evolution of carious lesions can be fast (acute) or slow (chronic). Both evolution rates are leading to loss of tooth 
structure over time and the morphology and function of teeth is affected. The goal of therapeutic procedures is to 
restore the morphology and function of teeth by replacing the missing tooth substance with restorative materials. 
There are two ways of therapeutic approaches to restore the lost tooth substance: In the case of a direct 
restorative procedures the tooth structure is restored directly in the oral cavity by a dentist with materials such as 
dental composites, amalgams or glass ionomers. For indirect procedures the tooth is prepared in a particular 
manner, so that insertion axes and material thicknesses of the final restoration are guaranteed. An impression of 
the preparation is taken, and the indirect restoration is manufactured in the dental laboratory. Indirect restorations 
are inlays, onlays, overlays, crowns and bridges. Materials such as glass ceramics and oxide ceramics, metal 
alloys and resin polymers are used for the fabrication of indirect restorations. The indirect restoration is cemented 
to the tooth with a luting cement or a luting composite. A digital approach is possible that implies a digital 
impression by the aid of an intraoral scanner. Then, the indirect restoration is designed on the computer with the 
support of a specific software (CAD computer aided design) and finally milled from a block or a disc in a specific 
milling unit (CAM computer aided manufacturing). The tooth preparation and the cementation of CAD-CAM 
restorations are similar to the conventional type of indirect restorations that imply impressions, a gypsum model 
and the manual fabrication by a dental technician. 
Dental adhesives provide the bond between direct restorative materials or luting composites and tooth structure. 
Dental adhesives are classified according to the historical evolution in generations from 1st to 8th generation, or 
according to the adhesion mechanism in etch and rinse adhesives, self-etch adhesives (Sofan et al. 2017).  
Universal adhesives belong to 1-step selfetching group. Regarding the polymerisation mechanism, dental 
adhesives can be grouped into light-, dual- or self-curing materials. When indirect restorations are adhesively 
cemented, the adhesive system is used in conjunction with a luting composite. The adhesive is applied on the 
tooth structure and afterwards it is either cured by a light curing unit before the restorations is inserted or it is 
cured together with the luting material. If the light curing option is chosen, the adhesive has to be applied in a very 
thin layer and has therefore to be thinned out very carefully with the air blast. Otherwise, the layer of adhesive 
could be too thick and could compromise the good fit of the restoration. The adhesive liquid has the tendency to 
accumulate in areas where it is difficult to control by air thinning, such as the transition from the cervical part of 
the proximal box to the axio-proximal part. If the adhesive is light cured in such a situation it will affect the fit of the 
final restoration. In this situation the restoration is too high and disturbs an adequate occlusion with the 
opposing teeth (hyperocclusion). A slight hyperocclusion can be corrected by grinding. However, a gross misfit 
affects not only the occlusion but also the marginal adaptation which sometimes makes the fabrication of a new 
restoration necessary. In order to avoid this shortcoming, dual-curing adhesive systems are available. They offer 
the benefit that no light curing of the adhesive layer is needed before the final restoration is seated. Another 
benefit of this type of adhesive system is that the polymerisation takes place and continues, even in areas that are 
not reached by the light of the light curing unit. The dual-curing adhesives possess initiators that guarantee a 
polymerization without any light activation. Therefore, a dual-cure universal adhesive combines the benefits of 
the universal adhesives with those of a dual-curing adhesive. Few data are available on the clinical performance 
of dual-cure universal adhesives. The primary aim of this clinical trial is to assess the rate of postoperative 
hypersensitivity and to compare it to the control group of an already performed study with a similar study design 
(NCT04475679). The secondary objectives are to assess the marginal adaptation and the retention/fracture rate 
of restorations, as well as the vitality and fracture rate of the restored teeth over a period of 5 years.  

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2. CLINICAL INVESTIGATION OBJECTIVES
2.1 Overall Objective
The aim of this study is to evaluate the clinical performance and safety of 
 for luting indirect ceramic 
restorations (inlays and onlays). 
2.2 Primary Objective
The investigation seeks primarily to determine the rate of postoperative hypersensitivity occurrence after using 
 for the placement of indirect restorations. The results will be compared to the control group (Adhese 
Universal) of a previously conducted clinical investigation. 
2.3 Secondary Objectives
The secondary objective of this study is to assess the long-term clinical performance of 
 in terms of 
marginal quality, retention/fracture rate of the ceramic restorations, and vitality/fracture rate of the restored teeth.  
2.4 Safety Objectives
The safety objectives are already covered in the primary and secondary objectives. This study aims to assess the 
long-term safety of 
 in terms of tooth vitality and failure rate of the placed restorations. Tooth vitality is an 
indicator for the health status of the dental pulp.  A vitality test is performed to acquire information about the vitality 
of teeth before and after the treatment. A healthy dental pulp offers a positive response to the vitality test. Once the 
dental pulp is injured an irreversible inflammatory reaction starts with a possible necrosis of the dental pulp. Pulpa 
necrosis is followed by a negative response to the vitality test. 

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3. CLINICAL INVESTIGATION OUTCOMES
3.1 Primary Outcome
Postoperative hypersensitivity is considered an indicator of the response of a tooth (pulp) to the therapeutic 
procedure applied. Postoperative hypersensitivity can be observed within a short time after the treatment. Therefore, 
it is assessed for the first time at the baseline recall (after 6-12days). The assessment of postoperative 
hypersensitivity includes questions about type and duration of pain, intensity of pain and on the stimulus inducing 
the pain (Hickel et al. 2007, Hickel et al. 2010, Hickel et al. 2022). The subjective perception of the intensity of 
postoperative hypersensitivity caused by thermal stimuli and caused by occlusal forces (during biting) will be 
determined by the aid of a Visual Analog Scale (VAS). The VAS values are brought into relationship to the 
preoperative values. In the table below a description of the correlation between FDI grade and VAS values and 
clinical signs and symptoms is shown. Not all signs need to be present at one stage. The exact VAS values vary 
widely from patient to patient, depending on each individual’s pain tolerance. Therefore, it is one of the factors 
influencing the FDI grade, but it is not directly correlated. Not all the described conditions have to be fulfilled to 
attribute an FDI score. Depending on the intensity and character of the pain, further therapy will be determined. 
Usually, postoperative hypersensitivity subsides spontaneously, and no treatment is necessary. In case of very 
intense pain an immediate treatment is required. The application of a fluoride varnish is the first procedure of choice. 
If no improvement is achieved by this method, then the replacement of the restoration would be the next step. In 
the worst case, the pulp is severely inflamed, requiring endodontic treatment. If the postoperative hypersensitivity 
does not subside spontaneously or worsens after the applied treatment, the highest assessed FDI value is used for 
the statistical analysis.  
For all participants a 1-month recall is planned to finally assess the postoperative hypersensitivity. The clinical 
experience of the evaluator is of major importance in the correct assessment of the FDI grade.  In general, the rule 
applies, that in case of uncertainties the higher score is attributed. 
FDI grade 
1 
2 
3 
4 
5 
Intervention 
none 
no 
treatment 
necessary 
fluoride varnish 
if desired 
replacement of 
restoration 
or 
endodontic 
treatment 
with 
access 
cavity 
only 
endodontic 
treatment 
and 
replacement of 
restoration 
Patient’s view / 
description 
of 
pain 
/ 
discomfort 
no complaint 
minor pain 
distinct pain 
persistent pain 
for 
prolonged 
period of time, 
patient asks for 
treatment 
treatment 
unavoidable 
VAS score 
0-3
<5 
>5
Pulp status 
none 
reversible pulpitis 
reversible 
or 
irreversible 
pulpitis 
irreversible 
pulpitis or pulp 
necrosis, with or 
without 
periapical 
periodontitis 
Duration 
of 
symptoms 
no symptoms 
<1 week 
>1 week
>1 month
n.a.
Vitality test 
normal, short reaction 
normal or more 
intense 
intense 
negative, 
nonvital 
tooth 
(no response) 
The assessment of the pulp status is done at all recalls following the 1-month recall because the pulp is exposed 
to lifelong stimuli and can react any time. The methods of assessment are as described above. VAS is only done if 
the patient feels any hypersensitivity.   
3.2 Secondary Outcomes
The secondary outcomes are the vitality, dental hard tissue defects at restoration margin and the retention/fracture 
rate of restorations. These parameters provide information about the clinical performance of the bond of the 
restoration to the tooth structure.  
Another secondary outcome is the marginal quality of the restorations that also provides information about the 
quality of the bond between tooth structure and luting composite.  

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The secondary outcomes will be assessed at all recalls with the respective FDI criteria (Hickel et al. 2022, Hickel 
et al. 2007; Hickel et al. 2010). 
3.3 Other Outcomes of Interest
Other outcome variables are translucency, colour match, surface gloss, form and contour, occlusion and wear of 
the ceramic restorations. These outcome variables provide information about the quality and stability of the lithium 
disilicate ceramic used for this type of restorations. 
3.4 Safety Outcomes
No other specific safety outcomes than the previous described (postoperative hypersensitivity, loss of vitality, loss 
of restoration, tooth fracture, tooth loss) will be evaluated. No laboratory parameters or other measurement or 
devices come to use in this clinical trial.  

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4.. CLINICAL INVESTIGATION DESIGN
4.1 General clinical investigation design and justification of design
 a new dental adhesive will be used to lute 45 inlays or onlays out of e.max CAD to teeth of at least 23 
patients. 
This prospective study has only one group (
) because the planed study is similar to a trial which has 
recently been executed in the internal clinic of Ivoclar Vivadent AG (NCT04475679).  The only difference to the 
already performed study is the device under assessment. Therefore, the coded results of the control group of the 
previous clinical investigation (Adhese Universal) will be compared with the clinical performance of the new dental 
adhesive (
).  
There are 5 operators and 2 evaluators. All operators are very experienced dentists in the field of restorative 
dentistry. The treatment of restoring teeth with ceramic inlays or onlays is a standard treatment in the internal clinic 
of Ivoclar Vivadent AG.   
Postoperative sensitivities arise within days after the treatment. Therefore, the occurrence of postoperative 
sensitivities can be assessed already at baseline. Final assessment of postoperative hypersensitivities will be 
performed at the 1-month recall. If such an incident is still present after 1 month, it will be followed regularly. 
The study duration of 5 years corresponds to the minimal duration recommended in restorative dentistry (Hickel et 
al., 2022). The patients will attend a recall after 6-12 days (baseline), 1, 6, 12, 24, 36, and 60 months.  
4.2 Methods for minimising bias
4.2.1 
Randomisation
This section is not applicable. 
4.2.2 
Blinding procedures
This section is not applicable. 
4.2.3 
Other methods for minimising bias
Confounding factors obscuring the 'real' effect of an exposure on outcome, will be controlled by inclusion and 
exclusion criteria. Attention is paid to equal gender distribution. 
To minimize the bias of the evaluation of product performance, the evaluators who independently assess the 
restorations do not place any restorations and are also not informed about who the operator was. The restorations 
are all produced by the same PM 7 CAD/CAM system from experienced dental technicians. Therefore, an influence 
of different CAD/CAM systems on the quality of the restorations can be excluded. Five different operators will place 
the restorations. This is important in order to minimize the effect of the handling of one single operator on the quality 
of the restorations.  
4.3 Unblinding Procedures (Code break)
None, as no blinding procedures are applied. 

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5. 
CLINICAL INVESTIGATION INTERVENTION
5.1 Identity of the medical device under investigation
5.1.1 
Experimental Intervention (medical device)
The newly developed dental adhesive 
 will be used together with a cement for luting an indirect restoration 
on tooth structure. 
 is a dual-curing single-component dental adhesive for enamel and dentin that is compatible with all 
etching techniques (self-etch, selective-enamel-etch, etch & rinse techniques). The product is indicated for both 
indirect restorations and direct restorations. In this clinical investigation, 
 in the VivaPen® (primary 
packaging) is used. VivaPen DC cannula (blue) is coated with the co-initiator required for the self-curing reaction. 
For hygienic reasons, a VivaPen protective sleeve is used by sliding the Pen with the cannula into the protective 
sleeve until the cannula punctures through the sleeve (Fig. 1). As described in the IFU, a new cannula and 
protective sleeve must be used for each patient. The 
 VivaPen can be re-used. By pressing the VivaPen 
push button (blue), the flocked cannula tip is saturated with adhesive liquid and mixes with the co-initiator. Following 
activation, the adhesive can be applied for approx. 120 seconds. Starting with the enamel the tooth surfaces to be 
treated need to be completely coated with 
. The adhesive must be scrubbed onto the tooth surface for at 
least 20 seconds. Then 
 is dispersed with oil- and moisture-free compressed air until a glossy, immobile 
film layer result. Since 
 is a dual curing material, it does not need to be light cured after application. Most 
adhesives on the market must be light cured. The application without light curing is of interest for this trial. The 
application of the material is in accordance with the instruction for use. 
A)
B)
Fig 1: A) 
 delivered in the VivaPen with the blue cannula for the dual curing adhesive and B) VivaPen with 
with protective sleeve. 
5.1.2 
Control Intervention (standard/routine/comparator)
This section is not applicable. 
Data will be compared with coded results of the control group (Adhese Universal) of a previously conducted clinical 
investigation ("Clinical evaluation of a new dual cure universal adhesive (Adhese Universal DC) in the indirect 
restorative therapy: A randomised, controlled clinical trial", NCT04475679). 

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6. STATISTICAL METHODS
The trial is a continuation of the clinical trial "Clinical evaluation of a new dual cure universal adhesive (Adhese 
Universal DC) in the indirect restorative therapy: A randomised, controlled clinical trial (NCT04475679)". The 
methodology, the endpoints and the hypothesis are the same. The test product 
 is a further development 
of Adhese Universal DC. In the planned clinical investigation, the test group will be compared to the control group 
(Adhese Universal) of the study mentioned above. The statistical considerations of the already performed study are 
re-used and are therefore mentioned in the paragraphs below.  
6.1 Hypothesis
The null hypothesis is that there is a statistically significant difference between control and test group with respect 
to postoperative hypersensitivity. 
The alternative hypothesis is that there is no difference between control and test group with regard to postoperative 
hypersensitivity. 
We do not expect in this equivalence study to find any statistical significance between control and test group with 
regard to postoperative hypersensitivity.  
6.2 Determination of Sample Size
The number of samples estimated to be needed for each study arm is 40 to achieve the objective. The G*Power 
sample calculator software Version 3.1.9.2 was used to determine the sample size, at a power of 80% and a type 
I error of 0.1 (Faul et al., 2007; Faul et al., 2009). 
Different to the previous study, this time a drop-out of 5 restorations is assumed. Therefore, the sample size aimed 
at is 45 instead of 40.  
6.3 Statistical criteria of termination of the investigation
The study will be terminated if more than 20% of the restorations fail (FDI grade 5 on any of the criteria). 
The study would be terminated prior to reaching baseline if more than 5 treated teeth were found to have post-
operative hypersensitivity (FDI 11 >grade 3). 
6.4 Planned Analyses
The IBM SPSS Version 25 software package will be used for data analysis. 
6.4.1 Datasets to be analysed, analysis populations
The data collected of all eligible participants that received a final restoration will be used for the statistical data 
analysis. 
6.4.2 Primary Analysis
Regarding the primary outcome, the interim analysis will be done at baseline. The final analysis of the primary 
outcome will be done after completion of the 1-month recall. The analysis will be done by the principal investigator 
within 3 months after the collection of the 1-month data. 
A non-parametric test (Mann-Whitney) between two independent groups will be used to compare the level of 
postoperative hypersensitivity (FDI 11) between the control and the test group. 
6.4.3 Secondary Analyses
Regarding the secondary outcomes, the analysis will be done after completion of the 1, 6, 12, 24, 36 and 60 months 
recall examinations, respectively. The analysis will be done by the principal investigator within 3 months after the 
collection of the baseline data. It will be a descriptive analysis. 
6.4.4 Interim analyses
The interim analysis will be done after the collection of data of the 6, 12, 24, 36 and 60 months recall examinations 
of all restorations. The analysis will be done by the principal investigator within 3 months after the collection of the 
recall data. In case of any further therapy related to the restorative intervention the restoration maybe regarded 
either as failure or as drop-out. Stopping guidelines are not necessary since the restorations are final interventions. 
No adjustment methods are needed for this clinical study since the interim analysis are for safety stopping reasons 
only.   
6.4.5 Deviation(s) from the original statistical plan
Deviations from the original statistical plan must be reported to the sponsor. 

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If a participant withdraws before all baseline examinations are completed, he/she will be replaced by another 
participant. Once all baseline examinations are completed, drop-outs are no longer replaced. There have only been 
few drop-outs and no-shows in the internal clinic in previous clinical trials so far. However, a drop-out of 5 
restorations was assumed. Therefore, 45 instead of 40 restorations will be placed. 
6.5 Handling of missing data and drop-outs

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7.  REFERENCES