Clinical Evaluation of a New Flowable Composite for Direct Restorative Treatment of Non-carious Cervical Lesions: A Prospective Randomized Split-mouth Study
Phase: NA
Conditions: Non-carious Cervical Lesions
Sponsor: Ivoclar Vivadent AG

 
Clinical evaluation of a new flowable composite for direct restorative treatment 
of non-carious cervical lesions: A prospective randomized split-mouth study 
Type of investigation: 
Clinical investigation concerning medical devices (MD). 
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 (unique single identification number: CIV-LI-
23-12-045054)
Identifier: 
OTCS 36419419 (Document ID: OTCS 36427036) 
Principal Investigator and 
Sponsor, or Sponsor-
Investigator: 
Principal Investigator (PI): 
Dr. med. dent. Carola Pentelescu 
Internal Clinic of Ivoclar Vivadent AG 
Bendererstrasse 2 
9494 Schaan 
Liechtenstein 
Tel. 
  
Mail: 
 
Sponsor: 
Ivoclar Vivadent AG 
Patrizia Elkuch-Hoch 
Team Leader Study Management 
Bendererstrasse 2 
9494 Schaan 
Liechtenstein 
Tel.: 
 
Mail: 
 
Sponsor representative (if the 
Sponsor is not located in 
Switzerland) 
n.a.
Medical Device: 
TM Flow (Ivoclar Vivadent AG) 
CIP Version and Date: 
Version 3.0, 17.01.2024 
CONFIDENTIAL 
The information contained in this document is confidential and the property of Ivoclar Vivadent AG (or 
“Sponsor”). 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) 
ID number of the OTCS 36419419 
investigation: 
Registry at ClinicalTrials.gov of the U.S. National Library of 
Medicine (http://www.clinicaltrials.gov) 
Title: 
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 (unique single identification number: CIV-Ll-
23-12-045054).
Clinical evaluation of a new flowable composite for direct 
restorative treatment of non-carious cervical lesions: A 
prospective randomized split-mouth study 
The Sponsor, the Principal lnvestigator and the Statistician have approved the CIP version 3.0 (dated 
17.01.2024) 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 
Signature 
Principal lnvestigator: Dr. med. dent. Carola Pentelescu 
Place/Date 
SigQ-
OTCS 36419419, Version 3.0 of 17.01.2024 
Page2 

OTCS 36419419, Version 3.0 of 17.01.2024 
Page 3 
Table of Contents 
SYNOPSIS .............................................................................................................................................. 4
ABBREVIATIONS ................................................................................................................................... 7
INVESTIGATION SCHEDULE ................................................................................................................ 8
1.
BACKGROUND AND RATIONALE ................................................................................................ 9
1.1 
Background and Rationale for the clinical investigation ................................................................ 9 
1.2 
Identification and description of the Investigational Medical Device ........................................... 10 
2.
CLINICAL INVESTIGATION OBJECTIVES ................................................................................. 11
2.1 
Overall Objective ......................................................................................................................... 11 
2.2 
Primary Objective ........................................................................................................................ 11 
2.3 
Secondary Objectives ................................................................................................................. 11 
2.4 
Safety Objectives ........................................................................................................................ 11 
3.
CLINICAL INVESTIGATION OUTCOMES ................................................................................... 12
3.1 
Primary Outcome ........................................................................................................................ 12 
3.2 
Secondary Outcomes .................................................................................................................. 13 
3.3 
Other Outcomes of Interest ......................................................................................................... 13 
3.4 
Safety Outcomes ......................................................................................................................... 13 
4.
CLINICAL INVESTIGATION DESIGN .......................................................................................... 14
4.1 
General clinical investigation design and justification of design ................................................. 14 
4.2 
Methods for minimising bias ........................................................................................................ 14 
4.2.1 Randomisation .................................................................................................................... 14 
4.2.2 Blinding procedures ............................................................................................................ 14 
4.2.3 Other methods for minimising bias ..................................................................................... 14 
4.3 
Unblinding Procedures (Code break) .......................................................................................... 14 
5.
CLINICAL INVESTIGATION INTERVENTION ............................................................................. 15
5.1 
Identity of the medical device under investigation ...................................................................... 15 
5.1.1 Experimental Intervention (medical device) ........................................................................ 15 
5.1.2 Control Intervention (standard/routine/comparator) ............................................................ 15 
6.
STATISTICAL METHODS ............................................................................................................. 16
6.1 Hypothesis ..................................................................................................................................... 16 
6.2 Determination of Sample Size ....................................................................................................... 16 
6.3 Statistical criteria of termination of the investigation ..................................................................... 16 
6.4 Planned Analyses .......................................................................................................................... 16 
6.4.1 Datasets to be analysed, analysis populations ..................................................................... 16 
6.4.2 Primary Analysis ................................................................................................................... 16 
6.4.3 Secondary Analyses ............................................................................................................. 17 
6.4.4 Interim analyses .................................................................................................................... 17 
6.4.5 Deviation(s) from the original statistical plan ........................................................................ 17 
6.5 Handling of missing data and drop-outs........................................................................................ 17 
7.
REFERENCES ............................................................................................................................... 18

OTCS 36419419, Version 3.0 of 17.01.2024 
Page 4
SYNOPSIS 
Sponsor / Sponsor-
Investigator 
Ivoclar Vivadent AG 
Title: 
Clinical evaluation of a new flowable composite for direct restorative treatment 
of non-carious cervical lesions: A prospective randomized split-mouth study 
Short title / 
Investigation ID: 
Split-mouth study of a new flowable composite in carious cervical lesions 
OTCS 36419419 
Clinical Investigation 
Plan, version and 
date: 
Version 3.0, 17.1.2024 
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 (unique single 
identification number: CIV-LI-23-12-045054). 
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 
TM Flow 
UDI not available 
Ivoclar Vivadent AG 
Benderer Strasse 2 
9494 Schaan 
SRN-number: LI-MF-000000522 
Stage of 
development: 
Pivotal stage  
The clinical investigation is conducted for a conformity assessment purpose. 
Background and 
rationale: 
Non-carious cervical lesions (NCCLs) are dish-shaped or wedge-shaped 
lesions, with well-defined margins and hard dentin on the surface. They are 
located in the cervical third of the tooth close to the cemento-enamel junction 
involving in the majority of cases the buccal face of teeth. They are widespread 
among middle age and older people. The cementoenamel junction proves to 
be more prone to loss of substance because the thickness of the enamel is 
greatly reduced. Also, the cervical area is considered the fulcrum of the tooth, 
where the stress accumulation during pressing, clenching or grinding 
parafunctions is the highest. These two factors lead to the loss of enamel and 
dentin in this area.  

OTCS 36419419, Version 3.0 of 17.01.2024 
Page 5
Objective(s): 
The overall objective of this clinical investigation is to evaluate the clinical 
safety and performance of the new flowable composite TM Flow. 
The primary objective is to assess the rate of postoperative hypersensitivity 
after treatment of non-carious cervical lesions with TM Flow and compare it to 
the treatment with the well-established flowable composite Tetric EvoFlow. 
The secondary objective of this study is to assess the long-term clinical efficacy 
of the materials under investigation in terms of marginal quality 
retention/fracture rate of the restorations and vitality. The color match, surface 
lustre and texture, contour and form, are also assessed. These outcomes 
provide information about the clinical performance of the material including the 
aesthetic performance. 
Outcome(s): 
The primary outcome of this clinical investigation is the rate of postoperative 
hypersensitivity after restoration of non-carious cervical lesions with TM Flow 
and respectively Tetric EvoFlow.  
The secondary outcomes focus on the clinical performance of the composites 
by evaluation of functional (e.g. fracture of the material and retention), 
biological (e.g. caries at restoration margins) and aesthetic (e.g. color match) 
properties of the restorations.  
The primary and the secondary outcomes are assessed using the FDI criteria 
(Hickel et al., 2022). 
Design: 
Randomized, controlled, prospective, double-blinded (patient and evaluator) 
split-mouth study design (test material: TM Flow, control material: Tetric 
EvoFlow in the same patient)  
Inclusion / exclusion 
criteria: 
Inclusion criteria: 
•
Informed Consent signed by the subject
•
Age: 18-65 years
•
2 NCCL needing treatment, comparable in extend and size, preferably
located in different quadrants
•
Vital teeth, regular sensitivity
•
Sufficient language skills
•
No active periodontitis
•
Preoperative VAS values < 3 regarding tooth sensitivity on biting. Tooth
sensitivity on temperature or touching (tooth brushing, probing)
originating in the area of the NCCL is accepted.
•
Subject wishes to have a restoration as part of the study (written
declaration of consent after detailed explanation)
Exclusion criteria: 
•
Not completed hygiene phase or poor oral hygiene
•
Sufficient isolation of the cavity not possible
•
Patients with a proven allergy to one of the ingredients (methacrylates)
•
Patients with severe systemic diseases
•
Periodontally insufficient dentition
•
Pregnancy
•
Part of the development project team of TM Flow
•
Staff of the study management team
•
Staff of the internal clinic
Measurements and 
procedures: 
Each participant receives two different fillings (test- and control material) in two 
different teeth. The fillings are assessed according to selected FDI criteria at 
baseline (7-10 days after filling placement) and after 1, 6, 12, 24, 36 and 60 
months. At each of these times points, the sensitivity is recorded using a visual 
analogue scale. The results are documented by intraoral images. 
Intervention: 
The newly developed flowable composite TM Flow will be used for the 
restoration of NCCLs in the test group. The treatment workflow is very similar 
to other flowable composites.  

OTCS 36419419, Version 3.0 of 17.01.2024 
Page 6
Control intervention 
(if applicable): 
The well-established Tetric EvoFlow will be used for the restorations of NCCLs 
in the control group. This material has been routinely used for such treatments 
in the internal clinic of Ivoclar Vivadent AG for many years.  
Number of subjects 
with rationale: 
66 patients are receiving 2 restorations because of the split-mouth study 
design. 
Duration of the 
investigation: 
60 months for each patient (recruiting phase 4 months) 
Investigation 
schedule: 
January 2024 First-subject-In 
December 2029 Last-subject-Out 
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 
Liechtenstein 
Statistical 
considerations: 
The sample size was calculated for a split-mouth design with a one-sided non-
inferiority hypothesis (target alpha 5%; power 80%).  
The obtained data of the test group will be compared with the data from the 
control group. 
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.  

OTCS 36419419, Version 3.0 of 17.01.2024 
Page 7
ABBREVIATIONS 
AE 
Adverse Event  
ADE 
Adverse Device Effect 
ASADE 
Anticipated Serious Adverse Device Effect 
ASR 
Annual Safety Report 
CA 
Competent Authority (e.g. Amt für Gesundheit, Liechtenstein) 
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 
NCCL 
Non-carious cervical lesions 
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 

OTCS 36419419, Version 3.0 of 17.01.2024 
Page 8
INVESTIGATION SCHEDULE 
Study Periods 
Screening 
Treatment, 
Intervention 
Period 
Follow-up 
Visit 
0 
1 
2 
3 
4 
5 
6 
7 
8 
Time (hour, day, 
week) 
-3- (-30) d
0 d 
7-10 d
1 m 
6 m 
12 m 
24 m 
36 m 
60 m 
Patient 
Information 
and 
Informed Consent 
x 
Medical History 
x 
In- 
/Exclusion 
Criteria 
x 
Tooth 
Examination 
x 
Pregnancy 
Test 
(only in case of 
uncertainty) 
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, 
x 
Randomization 
x 
Placement 
of 
restoration 
(test 
or control) 
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 
* Assessment will only be done if there is a patient complaint for paraesthesia or pain
** Not all variables will be assessed (only fracture of material, surface luster, color match) 

OTCS 36419419, Version 3.0 of 17.01.2024 
Page 9
1.
BACKGROUND AND RATIONALE
1.1 Background and Rationale for the clinical investigation
Non-carious cervical lesions (NCCLs) consist of irreversible loss of mineralized tissue unrelated to 
carious pathology (Walter et al., 2014). NCCLs are located in the cervical third of the tooth close to the 
cemento-enamel junction involving in the majority of cases the buccal face of teeth. The cementoenamel 
junction proves to be more prone to loss of substance because the thickness of the enamel is greatly 
reduced and, consequently, the enamel–dentin bond is much weaker (Walter et al., 2014). Also, the 
cervical area is considered the fulcrum of the tooth, where the stress accumulation during pressing, 
clenching or grinding parafunctions is the highest. These two factors lead to the loss of enamel and 
dentin in this area. Indeed, it has been seen that NCCLs are lesions present at all ages; however, 
epidemiological studies have pointed out a significant increase in their incidence at older ages (Borcic 
et al., 2004; Yang et al., 2016). Kolak et al. found that in a group of patients older than 55 years, 94.7 
percent of them had NCCLs, and one-third of them had more than three lesions (Kolak et al., 2018; 
Patano et al., 2023). Among the causes that lead to NCCL are abfraction, erosion, attrition and abrasion 
or combinations of those factors. NCCL are dish-shaped or wedge-shaped lesions, with well-defined 
margins and hard dentin on the surface. During the formation of the NCCL the dental pulp reacts and 
produces tertiary sclerotic dentin that obliterates the dentinal tubes and is found in the deeper areas of 
the NCCL. NCCL often associate with dentinal hypersensitivity due to the exposed dentin surfaces and 
the open dentinal tubuli. While small NCCL are treated by desensitising therapeutic procedures and the 
treatment of the aetiological factor the therapeutic approach changes when confronted with large NCCL. 
The presence of dentinal hypersensitivity, the increased plaque accumulation, the decreased 
mechanical tooth resistance and the aesthetic impairment (when the lesions are located in the frontal 
teeth) impose the necessity of a direct restorative therapeutic procedure. 
The materials that can be used for direct restorations of NCCL are either glass ionomer cement (GIC), 
resin modified GIC (RMGIC), compomers, giomers or dental composites. While RMGIC show a higher 
retention rate then flowable dental composites they show a poorer aesthetic and an increased water 
sorbtion (Patano et al., 2023).  Either flowable or packable dental composites can be used for the 
restoration of NCCL. When restored with a stiff hybrid composite resin, the clinical success rate was 
only 70% (McCoy et al., 1998). The high failure rate was attributed to the stiffness of the composite 
used. Thus, using a flowable composite resin with a lower flexural strength than traditional hybrid 
composites was assumed to improve the clinical success of these restorations. A one year clinical study 
evaluating Class V restorations using a flowable composite demonstrated that all restorations were 
intact and showed no signs of postoperative sensitivity after one year (Estafan et al., 1999). Many 
studies have concluded that the use of flowable composites for non-carious cervical lesions is a good 
choice (Kubo et al., 2010). There is only one research to compare the clinical efficacy of a flowable bulk-
fill composite to a standard nano-filled composite in the management of NCCLs. Its findings showed 
that both composites had acceptable clinical performances, despite minor changes in surface roughness, 
anatomic shape, and marginal adaptation after 1 year (Canali et al., 2019). So far, no clinical trial was 
found that compares the clinical performance of a bulk flowable composite and a regular flowable 
composite in the restoration of NCCL. 
Due to the shape of the cavities without any macro retentive element the retention is mainly dependent 
on the adhesion of the restoration to the tooth substance. This is above all dependent on the 
performance of the adhesive system used. The polymerization shrinkage and shrinkage stress also 
influence the adhesion of the restorations to the tooth structure as well as the C-factor (ratio bonded 
surfaces to unbonded surfaces of a restoration). Since the C factor is low in such a cavity it is reasonable 
to consider this type of direct restorative approach a suitable one.  
TM Flow is a bulk-flow dental composite that can be applied, and light cured in 4 mm thick layers with 
the exception of the shade A3,5 plus which can be polymerized in 3,5 mm layers. It can be cured in 10 
seconds at a light intensity of 1200 mW/cm2, 5 seconds at a light intensity of 2000 mW/cm2 or 3 seconds 
at a light intensity of 3000 mW/cm2. Not all polymerization modes are allowed to be used for each 
indication. The higher the light intensity may leads to a faster increase of the pulp temperature. The pulp 
temperature increase during polymerization might provoke a reaction of the dental pulp that is 
manifested clinically as postoperative hypersensitivity (pain) as a consequence of an inflammation. If 
the temperature increase is too high, the pulp tissue might undergo a sterile necrosis. Additionally, the 
exothermal polymerization reaction of dental composites is delivering also heat to the tooth contributing 
to the increase of the pulpal temperature. In general, flowable composites show a higher exothermal 
polymerization reaction then packable composites due to the higher monomer content. However, pre-
clinical investigations showed that the pulpal temperature increase after placing TM Flow fillings cured 
with 3000 mW/cm2 and 2000 mW/cm2 was not higher than that of the fillings cured with 1200 mW/cm2 

(OTCS 7218593). Therefore, it can be concluded that the use of higher light intensities for the 
polymerisation seem to be uncritical. 
Postoperative hypersensitivity can be caused by the incomplete seal of the dentinal tubuli, either due to 
the wrong application technique or the poor quality of the adhesive, or due to the high shrinkage of the 
dental composites, that pull of the material and the adhesive from the surface of the prepared cavity 
opening the dentinal tubuli. Another mechanism that might induce postoperative hypersensitivity during 
this CT is the high energy input delivered to the tooth during light curing of the materials in the Turbo 
mode plus the exothermic polymerization reaction of the materials. The sudden increase in the 
temperature represents a strong stimulus for the dental pulp that reacts by reversible or irreversible 
inflammation, clinically translated in postoperative hypersensitivity (pain). 
TM Flow is not bearing a CE mark and is not yet available on the market. No clinical studies have been 
conducted so far. The primary aim of this randomized controlled split-mouth clinical trial is to assess the 
incidence rate of postoperative hypersensitivity, when NCCL are directly restored with TM Flow 
respectively Tetric EvoFlow both light cured in the 5 seconds curing mode (Turbo Mode, 2000mW/cm2), 
since this is the mode with the highest energy output that is allowed for the use in NCCL. The use of TM 
Flow applied in a single layer of up to 4mm (3,5 mm in the case of the shade A3.5 plus) is considered 
the worst-case scenario, due to the higher exotherm polymerization reaction of the flowable composite 
regarding the incidence of postoperative hypersensitivity. Furthermore, the shrinkage stress is the 
highest during this approach, so it represents the worst case scenario in terms of marginal quality and 
retention rate. In this clinical investigation the clinical performance and safety of TM Flow will be 
compared with Tetric EvoFlow (a nano-hybrid flowable dental composite) in terms of pulp response of 
the teeth to the materials in combination with the 5 sec light curing mode (2000mW/cm2), marginal 
quality, retention rate, fracture of material, surface lustre and texture and other aesthetic properties.     
1.2 Identification and description of the Investigational Medical Device
This information is provided within the Investigator's Brochure (IB) and the Instructions for Use (IFU). 
Page 10

OTCS 36419419, Version 3.0 of 17.01.2024 
Page 11
2.
CLINICAL INVESTIGATION OBJECTIVES
2.1 Overall Objective
The aim of this clinical trial is to assess the clinical performance and safety of the new medical device 
TM Flow in direct restorative treatment (class V restorations). 
2.2 Primary Objective
The primary objective is to assess the rate of postoperative hypersensitivity after treatment of NCCLs 
with the new composite TM Flow and compare it to the treatment with the well-established composite 
Tetric EvoFlow. 
2.3 Secondary Objectives
The secondary objective of this study is to assess the long-term clinical efficacy of the materials under 
investigation in terms of marginal quality and retention/fracture rate of the restorations and vitality. The 
color match, surface lustre and texture, contour and form, dental hard tissue defects at the restoration 
margins are also assessed. These outcomes provide information about the clinical performance of the 
material including the aesthetic performance. 
2.4 Safety Objectives
This study aims to assess the long-term safety of TM Flow in terms of tooth vitality and failure rate of 
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.  A healthy dental pulp offers a positive 
response to the vitality test. Once the dental pulp is severely injured an irreversible inflammatory reaction 
starts with the endpoint of a necrosis of the dental pulp. Pulpal necrosis is followed by a negative 
response to the vitality test. 

OTCS 36419419, Version 3.0 of 17.01.2024 
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3.
CLINICAL INVESTIGATION OUTCOMES
3.1 Primary Outcome
The primary outcome in this clinical trial is the FDI criteria - B3 pulpal hypersensitivity and pulpal status 
(Hickel et al. 2022) 1 month after placing of the fillings. 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 7-10 days). The assessment of postoperative hypersensitivity 
includes questions about type and duration of pain, intensity of pain and on the stimulus inducing the 
pain. 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. 

OTCS 36419419, Version 3.0 of 17.01.2024 
Page 13
VAS is only done if the patient feels any hypersensitivity. 
3.2 Secondary Outcomes
A1 –Surface lustre and texture  
A2 – Marginal staining  
A3 – Color match  
F4- Form and contour    
F1- Fracture of material and retention  
F2- Marginal adaptation 
B1- Caries at restoration margins  
B2 – Dental hard tissue defects at the restoration margins 
M1 Patients view 
The FDI criteria and parameter will be used to evaluate the long-term performance of TM Flow 
restorations. These criteria were approved by the Science Committee of the FDI World Dental 
Federation (FDI) in 2007 and the General Assembly in 2008 as standard criteria that were specially 
designed for use in clinical studies (Hickel et al., 2007, Hickel et al., 2010).  
The retention/fracture rate of the restorations and the fracture rate of teeth (dental hard tissue defects 
at the restoration margins) are outcomes that provide information about the clinical performance of the 
bond of the restoration to the tooth structure and about the strength of the material and its ability to resist 
to the occlusal forces. 
Contact point, contour and form are secondary outcomes that provide information about the physical 
properties of the material and its ability to maintain its form when in clinical use. 
Colour match and surface lustre and texture are secondary outcomes that provide information about the 
aesthetic potential of the material. Surface lustre also proved information about the ability of the material 
to be polished to a level where plaque accumulation is reduced and the potential of the material to 
maintain its lustre over time. 
The marginal quality including marginal staining, dental hard tissue defects at the margin, marginal 
adaptation, caries at the margins of the restorations provides information about the quality of the bond 
between tooth structure and the dental composite. 
The secondary outcomes will be assessed at all recalls. 
3.3 Other Outcomes of Interest
n.a.
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. 

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4.3 Unblinding Procedures (Code break)
The operators and the PI are not blinded. Only the evaluator and the patients are blinded. If necessary, 
the evaluator gets information about the group allocation from the PI (for instance premature termination 
of the study).  
4.
CLINICAL INVESTIGATION DESIGN
4.1 General clinical investigation design and justification of design
A double blind (patient and evaluator), randomized, controlled, split mouth clinical trial is planned for TM 
Flow used to restore NCCL. The split mouth design allows the comparison of the two restorative 
materials under the same clinical circumstances. The materials are being exposed to the same oral 
conditions (microbiota, u oral hygiene, nutrition, saliva, chewing forces and if given parafunctions). The 
evaluation of postoperative hypersensitivity benefits from the study design, since this parameter is 
influenced by the individual perception on pain which vary widely among individuals. The risk for these 
interindividual variations is minimized by the use of the split mouth study design. 
66 patients will be included in this clinical investigation. Each patient will receive 2 restorations. The 
restoration belonging to the test group will be restored with TM Flow. The second restoration belonging 
to the control group will be restored with Tetric EvoFlow. The clinical procedure for both flowable 
composites is very similar, only the material differs. The randomization process will be performed 
electronically by the EDC platform Castor, which will also be used for the collection of data. The 
restorations will pe placed by 6 trained operators. Each operator will place at least 10 fillings. The 
evaluation of the restorations will be performed by an evaluator, that will be blinded and that has no 
information about the assignments of the restorations to each group.  
The duration of the clinical trial is 60 months. After the placement of the restorations, they will be 
evaluated at a baseline recall after 7-10 days and then after 1, 6, 12, 24, 36 and 60 months. At every 
recall postoperative sensitivity, teeth vitality, retention rate of restorations, color match, surface luster 
and texture, marginal integrity, form and contour, and contact points will be assessed according to FDI 
criteria (Hickel et al., 2022). Additionally, the margins of the restorations will be assessed by SQUACE 
(SemiQUAntitative Clinical Evaluation) according to the FDI criteria. 
The participants are recruited from the existing patient pool of the internal practice of Ivoclar Vivadent 
AG and are thus employees of the company. No active recruiting measures are taken. Each participant 
has the right to refuse participation in the clinical trial at any time. 
4.2 Methods for minimising bias
4.2.1 
Randomisation
Randomisation is performed electronically by Castor. Castor uses a validated variable block 
randomization model with optional stratification.  
4.2.2 
Blinding procedures
The evaluator will be blinded. The evaluator has only access to the recall eCRFs which contain no 
information regarding assignment of the restorations to the study groups. The patient is also blinded. 
The operator will not communicate the material which is used to treat the lesion. As long as the patient 
is lying on the dental chair it does not see the material, which is applied, therefore the patient does not 
know which tooth has received which material. 
4.2.3 
Other methods for minimising bias
n.a.

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5.
CLINICAL INVESTIGATION INTERVENTION
5.1 Identity of the medical device under investigation
TM Flow is a flowable, light-curing, radiopaque composite (200% Al) for the direct restorative treatment 
of anterior and posterior teeth.TM Flow cures with light in the wavelength range of 400–500 nm and can 
be applied in layers of up to 4 mm. 
5.1.1 
Experimental Intervention (medical device)
The direct filling therapy of an NCCL with a composite often in flowable consistency is an every day 
procedure for most dentists. The placement of this kind of filling is part of the basic training during dental 
medicine study. It is also described in many videos which are freely available. In the properties relevant 
to the application, test and control material differ only in the fact that TM Flow can be applied in thicker 
increments up to 4 mm compared with Tetric EvoFlow with 2 mm increment size and in slight difference 
in the consistency. 
For a patient it is often difficult to differentiate the exact tooth, which is responsible for a tooth ache. 
Therefore, experimental and control intervention can only be done at the same treatment session if the 
two teeth are located in different quadrants. Otherwise only one tooth can be treated in one visit. The 
second tooth can only be treated if the first tooth did not show any sign of postoperative sensibility or 
after the symptoms of postoperative sensibility have disappeared. After the first intervention at least the 
baseline visit needs to be waited for.  
5.1.2 
Control Intervention (standard/routine/comparator)
See 8.1.1 

6. STATISTICAL METHODS
6.1 Hypothesis
The Null Hypothesis (H0) is that the proportion of postoperative hypersensitivity occurrence after the 
treatment with the new composite (Ptreat) will be inferior to the treatment with an already established 
composite (Pcontrol). The alternative hypothesis (H1) is that the treatment with the new composite will be 
non-inferior to the standard treatment.  
The non-inferiority difference is a predefined margin of difference between the new treatment and the 
control treatment. The upper limit of the clinically acceptable proportion of postoperative hypersensitivity 
is 10% (proportion determined by experience). The actual proportion of patients experiencing 
postoperative hypersensitivity after a direct restorative treatment at the study site (internal clinic of 
Ivoclar Vivadent AG) is 2.4%. Therefore, the calculated non-inferiority difference is 7.6%. 
Split-mouth design with a one-sided non-inferiority hypothesis: 
H1: Ptreat - Pcontrol < 7.6% 
H0: Ptreat - Pcontrol ≥ 7.6% 
6.2 Determination of Sample Size
The sample size calculation was performed by Dr. Nicole Graf (biostatistician) from the Clinical Trials 
Unit of the Kantonsspital St. Gallen. Her CV and calculations can be provided upon request. 
The power was calculated using PASS Version 21.0.5 (PASS 2021 Power Analysis and Sample Size 
Software (2021). NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass.). 
Using the parameters listed in Table below, a sample size of 63 subjects achieves 80% power at a 
significance level of 0.05. 
Considering a drop-out of 3 patients, it is planned to include 66 patients in this study. 
Parameters used for the sample size calculation. 
Ptreat 
Pcontrol 
Actual 
difference 
Non-inferiority 
difference 
Nuisance 
parameter 
Target 
alpha 
Power 
Sample 
size 
0.024 
0.024 
0* 
0.076 
0.012 
0.05 
0.80 
63 
*It is expected that the treatment with the novel composite leads to a comparable proportion of patients with
postoperative hypersensitivity in comparison to the control treatment.
6.3 Statistical criteria of termination of the investigation
If 6 or more patients show a postoperative hypersensitivity of FDI grade 4 or 5 in test or control group 
the study will be terminated.  
6.4 Planned Analyses
The IBM SPSS Version 25 software package will be used for data analysis. 
The level of postoperative hypersensitivity between the control and the test group will be analysed. 
6.4.1 Datasets to be analysed, analysis populations
The data collected of all eligible participants that received two final fillings 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 1 month. It will be evaluated if the difference between postoperative 
hypersensitivity rate (FDI criterium B3) in test and control group is lower than the predefined non-
inferiority margin (7.6%). The analysis will be done by the principal investigator within 3 months after 
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the collection of the data. 
6.4.3 Secondary Analyses
Regarding the secondary outcomes, the analyses will be done after the 1, 6, 12, 24, 36 and 60 months 
recalls. Control and test group will be compared for each FDI criterium. The analysis will be done by the 
principal investigator within 3 months after the collection of the data.  
6.4.4 Interim analyses
The interim analysis will be done after the collection of data at each recall. The purpose is to compare 
in regular time intervals the results of the control group with those of the test group.  
6.4.5 Deviation(s) from the original statistical plan
Deviations from the original statistical plan must be reported to the sponsor. 
6.5 Handling of missing data and drop-outs
After baseline drop-outs will not be replaced. In previous clinical trials, there were few drop-outs in the 
internal clinic of Ivoclar Vivadent AG. There had also been a small number of no-shows. 

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Borcic, J.; Anic, I.; Urek, M.M.; Ferreri, S. The prevalence of non-carious cervical lesions in permanent 
dentition. J. Oral Rehabil. 2004, 31, 117–123. 
Canali, G.D.; Ignácio, S.A.; Rached, R.N.; Souza, E.M. One-year clinical evaluation of bulk-fill flowable 
vs. regular nanofilled composite in non-carious cervical lesions. Clin. Oral Investig. 2019, 23, 889–897. 
Estafan D, Schulman A, Calamia J. Clinical effectiveness of a Class V flowable composite resin system. 
Compendium of Continuing Education in Dentistry Journal. 1999, 20, 11-15. 
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: 121-147. 
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 Investig14(4): 349-366. 
Hickel, R.; Mesinger, S.; Opdam, N., Loomans, B.; Frankberger, R.; Cadenaro, M.; Burgess, J.; 
Peschke, A.; Heintze, S.D.; Kühnisch, J. Revised FDI criteria for evaluating direct and indirect dental 
restorations - recommendations for its clinical use, interpretation, and reporting. Clinical Oral 
7. References
Investigations 2022, 27, 2573-2592. 
Kolak, V.; Peši´c, D.; Melih, I.; Lalovi´c, M.; Nikitovi´c, A.; Jakovljevi´c, A. Epidemiological investigation 
of non-carious cervical lesions and possible etiological factors. J. Clin. Exp. Dent. 2018, 10, e648–e656. 
Kubo S, Yokota H, Yokota H, Hayashi Y. Three-year clinical evaluation of a flowable and a hybrid resin 
composite in non-carious cervical lesions. Journal of Dentistry. 2010; 38, 191-200. 
Levitch, L.C.; Bader, J.D.; Shugars, D.A.; Heymann, H.O. Non-carious cervical lesions. J. Dent. 1994, 
22, 195–207. 
McCoy RB. Clinical success of Class V composite resin restorations without mechanical retention. 
Journal of American Dental Association. 1998; 129, 593-99. 
Patano, A.; Malcangi, G. ; De Santis, M. ; Morolla, R. ; Settanni, V. ; Piras, F. ; Inchingolo, A.D. ;  
Mancini, A. ; Inchingolo, F. ;,  Dipalma, G.; Inchingolo, A.M. Conservative Treatment of Dental Non-
Carious Cervical Lesions: A Scoping Review. Biomedicines 2023, 11, 1530. 
Walter, C.; Kress, E.; Götz, H.; Taylor, K.; Willershausen, I.; Zampelis, A. The anatomy of non-carious 
cervical lesions. Clin. Oral Investig. 2014, 18, 139–146. 
Yang, J.; Cai, D.; Wang, F.; He, D.; Ma, L.; Jin, Y.; Que, K. Non-carious cervical lesions (NCCLs) in a 
random sampling community population and the association of NCCLs with occlusive wear. J. Oral 
Rehabil. 2016, 43, 960–966.