Treatment of Multiple Gingival Recession Defects With a Coronally Advanced Flap or a Modified Tunnel Technique and a Volume Stable Three-dimensional Xenogeneic Collagen Matrix: a Monocentric Randomized Clinical Trial
Phase: NA
Conditions: Gingival Recession
Sponsor: Università Vita-Salute San Raffaele

 
CLINICAL TRIAL PROTOCOL 
 
 
 
STUDY NUMBER: Fibro-Gide 
 
STUDY TITLE: Treatment of multiple gingival recession defects with a coronally advanced flap or a 
modified tunnel technique and a volume stable three-dimensional xenogenic collagen matrix: a monocentric 
randomized clinical trial. 
 
VERSION NUMBER: 3 
 
DATE: 21/02/2020 
 
N° CLINICALTRIAL.GOV: NCT04225351 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Promoter: Prof. Enrico Felice Gherlone 
 
 
 
Principal Investigator: Prof. Massimo de Sanctis       
 
 
 Date __/__/_____                                                                        ______________________________                     
 
 
 
 
 
 

 
2 
 
 
NAMES AND ADDRESSES OF  
 
Promoter 
 
Name: Prof. Enrico Felice Gherlone 
Address: gherlone.enrico@hsr.it 
 
 
Principal Investigator 
 
Name: Prof. Massimo de Sanctis 
Address: desanctis.massimo@hsr.it 
 
 
Co-Investigator 
 
Name: Giovanna Laura Di Domenico 
Address: giovannalauradd@gmail.com 
 
 
Clinical Monitor 
 
Name: Giovanna Bombelli 
Address: bombelli.giovanna@hsr.it 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
3 
 
 
TABLE OF CONTENTS 
 
 
 
1.         SYNOPSIS 
 
4 
2.         FLOW CHART 
 
5 
3.         INTRODUCTION AND RATIONALE 
 
6 
4.         STUDY OBJECTIVES 
     7 
4.1       Primary 
 7 
4.2       Secondary 
7 
 
5.         
 
STUDY DESIGN 
 
7 
5.1       Description of the protocol 
7 
5.2       Duration of study 
 
8 
6.         SELECTION OF PATIENTS 
8 
6.1       Inclusion criteria 
8 
6.2       Exclusion criteria 
 
8 
7.         STUDY PROCEDURES 
8 
7.1       Pre-treatment procedures 
8 
7.2       Surgical procedures 
9 
7.3       Study device 
10 
7.4       Post-operative procedures 
10 
7.5       Follow-up 
10 
7.6       Investigator training 
 
 
8.       STATISTICAL CONSIDERATIONS 
10 
8.1     Determination of sample size 
10 
8.2 
Null hypothesis 
10 
8.3     Statistical Methods 
 
11 
9.       ETHICAL AND REGULATORY CONSIDERATIONS 
11 
9.1     Informed Consent 
11 
9.2     Independent Ethics Committee Approval 
11 
9.3     Responsibilities of the investigator(s) 
12 
9.4     Responsibilities of the promoter 
 
12 
10.       DATA MANAGEMENT 
12 
10.1     Source Documents 
12 
10.2     Case Report Form (CRFs) 
 
12 
11.       DATA PROTECTION 
 
12 
12.  
 
13. 
 
14.      
DATA PROPERTY AND PUBLICATION POLICY 
 
GLOSSARY 
 
BIBLIOGRAPHIC REFERENCES 
13 
 
13 
 
14 

 
1. SYNOPSIS 
 
TITLE 
Treatment of multiple gingival recession defects with a coronally 
advanced flap or a modified tunnel technique and a volume stable 
three-dimensional xenogenic collagen matrix: a monocentric 
randomized clinical trial. 
TRIAL LOCATION 
PI: Prof. Massimo de Sanctis 
Dipartimento di Odontoiatria – Ospedale San Raffaele 
Direttore: Prof. Enrico Felice Gherlone 
STUDY OBJECTIVES 
To compare the outcomes of two muco-gingival surgery 
techniques, the modified coronally advanced flap (MCAF) for 
multiple recession defects (Zucchelli & de Sanctis 2000) and the 
modified coronally advanced tunnel technique (MCAT) (Aroca 
2013), performed in the Department of Periodontology of San 
Raffaele Hospital with the results reported in the literature. 
Secondarily, the study will evaluate whether patients report a 
preference in terms of discomfort and perception of aesthetics 
between the two surgical techniques. 
STUDY DESIGN 
Single center, National study, Comparative, Randomized, Open 
label 
STUDY POPULATION 
Main selection criteria: patients requiring root coverage 
procedures from the Dental Clinic of San Raffaele Vita-Salute 
University will be enrolled in the study. 
Inclusion criteria: multiple (i.e., at least 2) Miller Class I and/or II 
gingival recessions located in the maxillae,  good general health, 
healthy periodontal conditions (FMPS and FMBS <25%). 
Exclusion criteria: smoking >10 cigarettes/day,  nursing and 
pregnant 
female, 
contraindication 
against 
oral 
surgical 
interventions and against use of Fibro-Gide 
Total expected number of patients: 36 (18 for each group) 
STUDY PROCEDURES 
Recessions will be randomly treated by means of  MCAF + CM or 
MCAT technique + CM. The following measurements will be 
recorded at baseline (prior to surgery), at 90, 180 and 360 days: 
Gingival recession depth (REC in mm), Keratinized tissue width 
(KTW in mm), Gingival thickness (GT in mm), Pocket probing 
depth (PPD in mm), BoP (Bleeding on Probing, PI (Plaque Index). 
STUDY DEVICE 
Fibro-Gide 
STATISTICAL CONSIDERATIONS 
Hypothesis tested: no statistically significant differences are 
observed with respect to the clinical parameters CRC, at 12 
months between the two treatment modalities (i.e., MCAF + CM or 
MCAT technique with CM). 
Sample size calculation:  the needed number of patients to be 
enrolled in this study is 17 for the test group MCAF + Fibro-Gide 
and 17 for the MCAT + Fibro-Gide. However, the number of 
patients will be increased of 1 patient for each arm considering the 
possibility of dropout, so the required number will be 18 for each 
group. 
Primary method of analysis:   the significance of the difference 
within each group and between groups before and after treatment 
will be evaluated with the paired samples t-test or two independent 
samples t-test, as appropriated, regarding all numerical data 
(REC, KTW, GT, PPD, percentage of root coverage and VAS 
scale).  Fisher’s exact test will be applied for categorical data 
(frequency of complete root coverage). Differences will be 
considered statistically significant when the p-value was <0.05. 
DURATION OF STUDY PERIOD 
Global: 2 years 
Per patient: 1 years 

 
 
5 
 
 
2. FLOW-CHART 
 
 
Screening 
phase 
Study phase 
End  
of study 
Evaluation 
Screening 
Surgery 
Post treatment follow-up 
 
 
 
Day 0 
Day 
7±2 
Day 
14±4 
Day 
30±7 
Day 
90±15 
Day 
180±30 
Day 
360±60 
Demographic data 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria 
X 
 
 
 
 
 
 
 
Previous medical history 
X 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
Clinical examination 
X 
 
 
 
 
 
 
 
PPD, BoP, PI 
X 
 
 
 
 
X 
X 
X 
REC, KTW, GT 
X 
 
 
 
 
X 
X 
X 
Oral hygiene instructions 
X 
X 
 
X 
 
 
 
 
Treatment 
Randomization 
 
X 
 
 
 
 
 
 
Mucogingival surgery 
 
X 
 
 
 
 
 
 
Use of Fibro-Gide 
 
X 
 
 
 
 
 
 
Compliance 
 
 
X 
X 
X 
X 
X 
X 
Suture removal 
 
 
 
X 
 
 
 
 
Photography 
 
X 
X 
X 
X 
X 
X 
X 
Pain assessment (VAS) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
6 
3. INTRODUCTION AND RATIONALE 
Gingival recession is defined as the exposure of the root surface due to the displacement of the 
gingival margin apical to the cement-enamel junction (CEJ) (Armitage 1999; Wennstrom 1996). It 
was estimated that >20% of the population presents one or more tooth surfaces exhibiting recessions 
(Albandar and Kingman,1999). The development of gingival recessions can often be associated with 
mechanical factors (trauma caused by excessive tooth brushing, orthodontic therapy or piercing), or 
inflammatory periodontal disease (Graziani 2014). The exposed root surfaces are frequently 
associated with esthetic complaints, root hypersensitivity and difficulties in achieving optimal plaque 
control (Cairo 2017). 
The progression of gingival recessions should be evaluated in individuals with a high level of plaque 
control (Matas 2011). 
Furthermore, a recent systematic review assessed the prognosis of untreated gingival recessions and 
found that only 21.9% of sites with gingival recession at baseline did not increase in recession severity 
during a 2-year follow-up period, and that 79.3% of patients showed an increase in the number of 
recession defects (Cairo 2017; Chambrone 2016).  
Results from systematic reviews indicate that at single Miller (Miller, 1985) Class I and II gingival 
recessions complete root coverage (CRC) can predictably be obtained when using the modified 
coronally advanced flap (MCAF) technique, with and without soft tissue grafting and/or biologic 
agents, such as an enamel matrix derivative (Cairo 2014; Chambrone 2010). 
On the other hand, the treatment of multiple gingival recessions appears to be more challenging for 
the clinician and due to limited evidence, no recommendation can be made to support the selection 
of one technique over another (Tonetti 2014); but modified CAF and tunnel approaches show higher 
level of complete root coverage (CRC) (Graziani 2014). 
During the discussion of a recent meta-analysis, Graziani reported that despite the “ideal” treatment 
is not yet identified, there are some indirect suggestions from the analyzed data that, in comparison 
to the traditional CAF approach, the use of additional grafting, modifications of the flap technique or 
tunnel variation with connective tissue graft (CTG) may improve clinical results (Graziani 2014). 
Findings from a long-term study, suggest that, in patients with a high standard of oral hygiene, 
enrolled in a regular maintenance care program, shallow recessions may further deteriorate over a 
period of 10 to 27 years. On the other hand, treatment of contra-laterally located recessions by means 
of gingival-augmentation techniques showed long-term stability and a tendency for coronal 
displacement of the gingival margin with a reduction in recession depth (Agudio 2009). These results 
are in line with those from a 5-year follow-up split mouth study comparing the clinical outcomes of 
the modified coronally advanced flap (MCAF) alone, versus the coronally advanced flap plus 
connective tissue graft (CAF + CTG) in the treatment of multiple gingival recessions (Pini-Prato 
2010). Over a short period (e.g., up to 6 months), both treatments resulted in comparable outcomes 
in terms of root coverage. However, at the 5-year follow-up, the sites treated with CAF alone 
demonstrated an apical relapse of the gingival margin, whereas the sites grafted with CTG showed 
not only stability, but even a coronal improvement of the gingival margin, as compared to the 6-
month results (Agudio 2009; Pini-Prato 2010). 
CTG harvesting is often associated with increased patient morbidity, prolonged surgical time and the 
possibility of postoperative complications such as bleeding, numbness and sensibility changes at the 
donor area (Aroca 2013; Buff 2009; Reiser 1996). Various allografts or replacement biomaterials 
have been developed instead of a connective tissue graft in order to reduce patient morbidity (Aroca 
2013; Thombre 2013 Cordaro 2012; Aroca 2009). A newly developed porcine-derived bio-resorbable 

 
 
7 
collagen matrix (CM) (Fibro-Gide) has been recently introduced as an alternative to CTG in 
periodontal plastic surgery. 
These mucogingival surgical techniques are routinely used to treat recessions by clinicians of 
Department of Periodontology of Dental Clinic of San Raffaele Hospital and they are present in the 
list of dental services provided with code “ODCMCM”. 
 
4. STUDY OBJECTIVES 
The aim of this study will be to compare the outcomes of two muco-gingival surgery techniques, the 
modified coronally advanced flap (MCAF) for multiple recession defects (Zucchelli & de Sanctis 
2000) and the modified coronally advanced tunnel technique (MCAT) (Aroca 2013), performed in 
the Department of Periodontology of San Raffaele Hospital with the results reported in the literature. 
Secondarily, the study will evaluate whether patients report a preference in terms of discomfort and 
perception of aesthetics between the two surgical techniques. 
 
4.1. Primary outcome 
- percentage (%) of complete root coverage (CRC) at 12 months 
 
4.2. Secondary outcomes 
- percentage of root coverage (RC %) at 3, 6 and 12 months 
- keratinized tissue width (KTW) at 3, 6 and 12 months 
- gingival thickness (GT) at 3, 6 and 12 months 
- post-surgical pain (PP), 
- amount of drug intake after surgery 
- patient perception of aesthetics at 6 and 12 months 
- color match (blending), contour (correct outline of the gingival margin at adjacent teeth), 
contiguity (evaluated based on the visible confluence between the treated area and the adjacent 
soft tissues), degree of keloid formation scored at the 1-year post-surgical evaluation will be 
measured by an expert periodontist. 
- duration of surgery (from anesthesia to last suture). 
 
 
5. STUDY DESIGN 
5.1. Description of the protocol 
The present research is a monocentric prospective parallel randomized controlled clinical trial. 
Patients presenting multiple gingival recessions in the maxillae will be enrolled in the study after 
having signed an informed consent. Recessions will be treated by means of two mucogingival surgery 
techniques: modified coronally advanced flap (MCAF) and  modified coronally advanced tunnel 
technique (MCAT), in association with the use of a collagen matrix (CM). 
An allocation sequence by means of a computer-generated random list will be created and a sealed 
opaque envelope will contain the type of treatment assigned to each patient. The opaque envelope 
will be opened immediately after performing anesthesia. 
 

 
 
8 
5.2. Duration of study 
Each patients will be followed for 12 months after surgery. 
6. SELECTION OF PATIENTS 
The present study will be reported according to the CONSORT statement for improving the quality 
of reports of parallel-group randomized trials (http://www.consort-statement.org/). This will be a 
parallel monocentric prospective randomized controlled clinical trial. 
Patients requiring root coverage procedures from the Department of Periodontology of San Raffaele 
Hospital will be enrolled in the study. 
 
6.1. Inclusion criteria 
Subjects must be males and females of at least 18 years of age with: 
- multiple (i.e., at least 2) Miller Class I and/or II gingival recessions located in the maxillae, with 
an apico-coronal extension (i.e., defect depth > 1 mm with at least one defect > 2 mm) and with at 
least 1 mm of residual keratinized tissue, 
- good general health, with no systemic diseases that could influence the outcome of the therapy, 
- healthy periodontal conditions (i.e., no presence of sites ≥ 4 mm and/or presence of intra-bony 
defects in the selected sites), 
- adequate oral hygiene (full mouth plaque score (FMPS) of <25% at baseline (following initial oral 
hygiene instructions and prophylaxis), 
- an adequate control of inflammation (full mouth bleeding score [FMBS]) of <25% at baseline 
(following initial oral hygiene instructions and prophylaxis). 
 
Subjects must have voluntarily signed the informed consent before any study related action and must 
be committed to the study and the required follow-up visits. 
 
6.2. Exclusion criteria 
- subjects who currently smoke >10 cigarettes/day, 
- female subjects who are nursing, pregnant, or plan to become pregnant, 
- contraindication against oral surgical interventions, 
- contraindication against use of Fibro-Gide (acute infection in the area of surgery and patient with 
collagen allergy) 
 
7. STUDY PROCEDURE 
7.1. Pre-treatment procedures 
Cause-related therapy will be completed on all patients prior to surgery. In particular, patients will 
receive oral hygiene instructions (roll technique) to eliminate the wrong habits related to the etiology 
of the recession at least 2 months before surgery. 
 
7.2. Surgical procedures 
Two experienced practitioners (M.d.S. and S.A.) will perform the surgical session according to the 
technique as presented by Zucchelli & de Sanctis 2000 and Aroca et al. 2013. 
- Modified coronally advanced flap (MCAF) 

 
 
9 
After local anesthesia, a horizontal incision is made to include one tooth on each side of the teeth to 
be treated. The horizontal incision of the envelope flap consists of oblique sub-marginal incisions in 
the interdental areas, incisions which continue with the intra-sulcular incision at the recession defects.  
Each surgical papilla (SP) is dislocated with respect to the anatomic papilla by the oblique sub-
marginal interdental incisions; in particular, the surgical papilla mesial to the flap midline are 
dislocated more apically and distally, while the papilla distal to the mid-line are shifted in a more 
apical and mesial position. 
The envelope flap is raised with a split-full-split approach in the coronal-apical direction: the surgical 
papilla is dissected in a split-thickness manner, while gingival tissue apical to the root exposures is 
raised in a full-thickness manner (to provide that portion of the flap critical for root coverage with 
more thickness).  Finally, the most apical portion of the flap is elevated in a split-thickness manner 
to facilitate the coronal displacement of the flap. 
The portion of the root exposure with loss of clinical attachment (gingival recession plus probeable 
gingival sulcus/pocket) are mechanically treated with the use of curettes and EDTA is applied for 2 
minutes. 
The remaining tissue of the anatomic interdental papilla is de-epithelialized to create connective tissue 
beds to which the surgical papilla are sutured. 
A sharp dissection into the vestibular lining mucosa is then carried out to eliminate muscle tension. 
Flap mobilization is considered “adequate” when the marginal portion of the flap is able to passively 
reach a level coronal to the CEJ at each single tooth in the surgical site. The flap, in fact, should be 
stable in its final position even without the sutures. 
The porcine-derived bio-resorbable collagen matrix (CM) (Fibro-Gide) is now prepared for 
placement on the interested areas: the width of the matrix must be reduced to 3-4 mm  and the matrix 
has to adapt to the receiving tissues, when placed, a suture (6/00) must be used to hold it in position.  
Sling sutures (6/00) are performed to accomplish a precise adaptation of the buccal flap on the 
exposed root surfaces and to stabilize every single surgical papilla over the interdental connective 
tissue bed.   
- Modified coronally advanced tunnel technique (MCAT) 
Immediately before surgery, composite stops are placed at the contact points to prevent collapse of 
the future suspended sutures into the inter-proximal spaces.  
After local anaesthesia, root planing of the exposed root surface is performed by means of hand 
instruments. Ethylenediaminetetraacetic (EDTA) is applied on the sites.  
Subsequently, intra-sulcular incisions were placed and muco-periosteal flap separation are raised 
using sharp tunnel elevators. The muco-periosteal dissection is extended beyond the muco-gingival 
junction (MGJ) and under each papilla, to allow passive, tension-free mobilization in coronal 
direction. Muscle fibres and any remaining collagen bundles on the inner aspect of the flap alveolar 
mucosa are cut using Gracey curettes with extreme care in order to obtain a passive coronal 
positioning of the flap and the papilla and to avoid perforation of the flap.  
The porcine-derived bio-resorbable collagen matrix (Fibro-Gide) is now prepared for placement on 
the interested areas: the width of the matrix must be reduced to 3-4 mm, then it can be inserted under 
the CAMT by starting at the deepest recession. Then, the site is rinsed with saline solution to remove 
any clot. The matrix has to be held in position using a suture (6/00).   
Finally, the flap is positioned coronally to CEJ by means of suspended sutures (6/00) around the 
contact points.  
At surgery, the duration of the full procedure will be evaluated (from anesthesia to suture). 
 

 
 
10 
7.3. Study device 
Fibro-Gide, a porcine, porous, resorbable and volume-stable collagen matrix, will be used for this 
investigation.  It is a class III medical device according to the Medical Device Directive 93/42 EEC’s 
definition: 1.1. long term implant, 1.2. implantable and rules 8 (resorbable) and 17 (animal origin). 
The material is weakly cross linked using EDC ((1-ethyl-3-3-dimethylaminopropyl) carbodiimide). 
CE certificate G7 1607 39446 073 for Geistlich Fibro-Gide® was issued on 12.08.2016 for the 
intended use of soft tissue augmentation in the oral cavity. 
All matrices will be provided by Geistlich as a contribute to the project. 
  
7.4. Post-operative procedures 
Post-surgically, all patients will be given antibiotics for 6 days and were instructed to rinse their 
mouth with a 0.2% chlorhexidine solution, three times a day for 1 min. for 1 months.  
Patients will be instructed to avoid brushing in the operated area until 2 weeks after surgery and 
instructed in mechanical tooth cleaning using a soft toothbrush. 
All patients will be recall after 1, 2 and 4 weeks. They will be further recalled 3, 6 and 12 months 
after surgery for professional oral hygiene procedures and measurements. 
 
7.5. Follow-up 
Patients will be followed for 12 months after surgery. 
At 7 ± 2 days post-surgery – general examination, photographic picture of the treated site 
questionnaire about post-operative pain. 
At 14 ± 4 days post-surgery – suture removal, photographic pictures of the treated site  
At 1 month ± 7 days post-surgery – general examination, photographic picture of the treated site  
At 3 months ± 15 days post-surgery - general examination, photographic picture of the treated site, 
measurements of the following parameters: Gingival recession depth (REC in mm), Keratinized tissue 
width (KTW in mm), Gingival thickness (GT in mm), Pocket probing depth (PPD in mm), BoP, PI. 
At 6 ± 1 months post-surgery - general examination, photographic picture of the treated site, 
evaluation of the aesthetic outcome, measurements of the following parameters: Gingival recession 
depth (REC in mm), Keratinized tissue width (KTW in mm), Gingival thickness (GT in mm), Pocket 
probing depth (PPD in mm), BoP, PI. 
At 12 ± 2 months post-surgery - general examination, photographic picture of the treated site, 
evaluation of the aesthetic outcome, measurements of the following parameters: Gingival recession 
depth (REC in mm), Keratinized tissue width (KTW in mm), Gingival thickness (GT in mm), Pocket 
probing depth (PPD in mm), BoP, PI. 
 
7.6. Investigator training 
Five subjects not involved in the study, each showing a pair of single-rooted contra-lateral teeth with 
recessions > of 2 mm on the mid-buccal aspect of each tooth, will be used to calibrate the examiner. 
The examiner will evaluate the subjects on two occasions 24 h apart. Calibration will be accepted if 
90% of the recordings could be reproduced within a difference ≤ 0.5 mm (Aroca 2010).  
 
 
 
8. STATISTICAL CONSIDERATIONS 
8.1. Sample size calculation 

 
 
11 
The range of mean root coverage percentage of the two mucogingival techniques which can be found 
in literature varies between 85% and 95%. While the value of variability (SD) obtained in previous 
articles is 10%. On the basis of these settings, the sample dimension has been calculated using a = 
0.05 and the power (1-b) of 80%. The minimal significant value considered is 10%.  
So, the needed number of patients to be enrolled in this study is 17 for the test group MCAF + Fibro-
Gide and 17 for the MCAT + Fibro-Gide. However, the number of patients will be increased of 1 
patient for each arm considering the possibility of dropout, so the required number will be 18 for each 
group. 
 
8.2. Null hypothesis  
H0: No statistically significant differences are observed with respect to the clinical parameters CRC, 
at 12 months between the two treatment modalities (i.e., MCAF + CM or MCAT technique with CM). 
 
8.3. Statistical Methods 
Statistical analysis will be performed using commercially available software (STATA) or R 
environment (www.r-project.org). Both patient- and tooth-level analysis will be performed for each 
parameter. Therefore, mean values and standard deviations (SD), as well other descriptive statistics, 
for the clinical variables will be calculated for each patient per treatment.  
A mixed model will be built to take into account the variability due to patient and tooth factors 
differentially. 
Accordingly, the significance of the difference within each group and between groups before and 
after treatment will be evaluated with the paired samples t-test or two independent samples t-test, as 
appropriated, regarding all numerical data (REC, KTW, GT, PPD, percentage of root coverage and 
VAS scale). 
Fisher’s exact test will be applied for categorical data (frequency of complete root coverage). 
P-values will be computed by means of permutation methods to avoid any distributional assumptions 
or asymptotical approximation. Differences will be considered statistically significant when the p-
value was <0.05. 
9. ETHICAL AND REGULATORY CONSIDERATIONS 
This clinical trial will be conducted in accordance with the principles laid down by the 18th World 
Medical Assembly (Helsinki, 1964) and all applicable amendments laid down by the World Medical 
Assemblies, and the ICH guidelines for Good Clinical Practice. 
This clinical trial will be conducted in compliance with all international laws and regulations, and 
national laws and regulations of the country in which the clinical trial is performed, as well as any 
applicable guidelines. 
 
9.1. Informed consent 
The investigator (according to applicable regulatory requirements), or a person designated by the 
investigator, and under the investigator's responsibility, should fully inform the Patient/Subject of all 
pertinent aspects of the clinical trial. All participants should be informed to the fullest extent possible 
about the study, in language and terms they are able to understand. 
Prior to a patient’s/subject’s participation in the clinical trial, he/she MUST signed the written 
Informed Consent Form. 
It must also be made clear to the patient/subject that he/she can withdraw from the study at any time 
without giving reasons and that he/she will not be in any way disadvantaged by this. 

 
 
12 
The Informed Consent Form must be approved by Independent Ethics Committee. 
Any Informed Consent will be part of Investigator’s file and retained with it. A copy of the signed 
and dated written Informed Consent Form must be provided to the patient/subject. 
 
9.2. Independent Ethics Committee Approval (IRB/IEC) 
This clinical trial protocol as well as the Informed Consent are to be submitted to the appropriate 
Ethics Committee, and it is mandatory to obtain the written and dated approval/ favorable opinion, 
signed by the chairman with ethics committee(s) composition. 
The clinical trial (study number, clinical trial protocol title and version number), the documents 
reviewed (clinical trial protocol, Informed Consent Form, Investigator’s Brochure, investigator’s CV, 
etc.), the list of voting members and their qualifications and the date of the review should be clearly 
stated on the written ethics committee approval/favorable opinion. 
 
9.3. Responsibilities of the investigator(s) 
The investigator(s) undertake(s) to perform the clinical trial in accordance with this clinical trial 
protocol, ICH /Good Clinical Practice and the applicable regulatory requirements. 
The investigator is required to ensure compliance with all procedures required by the clinical trial 
protocol and with all study required procedures. The investigator agrees to provide  all information 
requested in the Case Report Form (CRF) in an accurate and legible manner. 
Furthermore, the investigator commits to give immediate notice of any Adverse Event and/or Serious 
Adverse Event (AE/SAE). 
 
10. DATA MANAGEMENT 
10.1. 
Source Documents 
According to the ICH /Good Clinical Practice, the monitoring team must check the Case Report Form 
entries against the source documents. 
 
10.2. 
Case Report Forms (CRFs) 
It is the responsibility of the investigator to maintain adequate and accurate CRFs (according to the 
technology used). All CRFs should be completed in their entirety in a neat, legible manner to ensure 
accurate interpretation of data. 
Should  a  correction  be  made,  the  information  to  be  modified  must  not  be  overwritten.  The 
corrected information should be transcribed by the authorized person next to the previous value, 
initialed and dated. 
11. DATA PROTECTION 
The investigators ensure that all safeguards are in place to minimize any eventual risk of breaches 
and comply otherwise with requirements of GDPR as implemented in its policy on data protection. 
Patient data collected will be anonymized (a number will be assigned at each patient) and all 
documents will be stored in locked security cabinets in controlled areas. 
The investigators regularly check all their procedures relevant to the processing of personal data, so 
that it ensures privacy by design and compliance with GDPR. 
12. DATA PROPERTY AND PUBLICATION POLICY 
Clinical study data are property of Department of Periodontology of San Raffaele Hospital.  

 
 
13 
The results of this study will be submitted for publication primarily in peer-reviewed journals, or as 
abstracts, posters, or other presentations at scientific meetings. 
 
13. GLOSSARY 
• AE/SAE - adverse event/serious adverse event 
• BoP - Bleeding on probing  
• CAF - coronally advanced flap  
• CEJ - cement-enamel junction 
• CRC - complete root coverage  
• CRF – case report form 
• CTG - connective tissue graft  
• CM - collagen matrix  
• EDTA - Ethylenediaminetetraacetic  
• FMBS - full mouth bleeding score 
• FMPS - full mouth plaque score  
• GT - gingival thickness  
• KTW - keratinized tissue width  
• MCAF - modified coronally advanced flap 
• MCAT - modified coronally advanced tunnel technique 
• MGJ - muco-gingival junction   
• RC % - percentage of root coverage  
• REC - gingival recession depths 
• PI - plaque index 
• PP - post-surgical pain  
• PPD - pocket probing depth  
 
14. BIBLIOGRAPHIC REFERENCES 
- Agudio G, Nieri M, Rotundo R, Franceschi D, Cortellini P, Pini Prato GP. Periodontal conditions 
of sites treated with gingival-augmentation surgery compared to untreated contralateral 
homologous sites: a 10- to 27-year long- term study. J Periodontol 2009; 80:1399–1405. 
- Albandar JM, Kingman A. Gingival recession, gingival bleeding, and dental calculus in adults 30 
years of age and older in the United States, 1988–1994. J Periodontol 1999; 70:30–43.  
- Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann 
Periodontol 1999; 4:1–6. 
- Aroca S, Keglevich T, Barbieri B, Gera I, Etienne D. Clinical evaluation of a modified coronally 
advanced flap alone or in combination with a platelet-rich fibrin membrane for the treatment of 
adjacent multiple gingival recessions: a 6-month study. J Periodontol 2009; 80:244–252. 
- Aroca S, Molnar B, Windisch P, et al. Treatment of multiple adjacent Miller class I and II gingival 
recessions with a Modifed Coronally Advanced Tunnel (MCAT) technique and a collagen matrix 
or palatal connective tissue graft: a randomized, controlled clinical trial. J Clin Periodontol 2013; 
40:713–720. 

 
 
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- Cairo F, Nieri M, Pagliaro U. Efficacy of periodontal plastic surgery procedures in the treatment 
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