Efficacy of Combined Air-abrasive+Ultrasonic (Guided Biofilm Therapy GBT) vs. Standard Root Debridement (Scaling and Root Planing+ Ultrasonic SRP+US) in the Treatment of Severe Generalized Periodontitis: A Randomized Clinical Trial
Phase: NA
Conditions: Periodontitis, Aggressive, Periodontal Diseases, Periodontitis
Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

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Strictly Confidential 
 
Efficacy of combined Air-abrasive + Ultrasonic (FM-
EPAPT) vs. standard root debridement in the treatment 
of severe generalized periodontitis. 
A prospective, single-masked, randomized, split-mouth, 
longitudinal clinical and microbiological trial. 
 
 
 
 

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Contents 
 
 
1.           Study summary 
 
 
1.1.        Introduction 
1.2         Background information  on  Air Polishing and Perio-Flow EMS 
 
1.3         Rationale for clinical study Air-Polishing and Perio-Flow in the treatment of periodontitis 
1.4  
Study design  
1.5  
Study period   
1.6  
Study setting  
1.7  
Patients: 
1.8  
Main Inclusion criteria:   
1.9  
Main Exclusion criteria:  
1.10  
Preoperative evaluation:  
1.11  
Treatment procedure:  
1.12  
Main outcome measures  
1.13  
Adverse event evaluation and reporting:  
 
2. 
Hypothesis and study objectives 
 
2.1   
Null hypothesis and alternate hypothesis 
 
2.1.1  
H0  
 
2.1.2  
HA  
 
2.2 
Primary Objective  
 
2.3 
Secondary Objectives 
 
3  
Intervention 
 
3.1  
Treatment procedure 
 
3.2  
Examinations 
 
4 
STUDY SUBJECTS CRITERIA AND STUDY METHODS 
 
4.1 
Inclusion criteria 
 
 
4.2      
Exclusion criteria 
 
4.3 
Withdrawal criteria 
 
4.4 
Schedule of investigational procedures 
 
4.5 
PREOPERATIVE PROCEDURES –  
 
4.6 
PEROPERATIVE PROCEDURES – 
 
4.7 
CONTROL TREATMENT 

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4.8 
TEST TREATMENT 
 
4.9 
POSTOPERATIVE FOLLOW-UP PROCEDURES -  
 
4.10 
 CASE REPORT FORMS 
 
5. 
ADVERSE EVENTS    
 
6. 
PATIENT INFORMATION AND CONSENT 
 
 
7. 
STATISTICAL ANALYSIS 
 
7.1.     SAMPLE SIZE 
 
7.2.     STATISTICAL EVALUATION 
 
 
 

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1. STUDY SUMMARY 
 
 
1.1.  Introduction 
 
Periodontitis is a widely diffused infectious disease. Over 700 million people worldwide are 
supposed to suffer from it, in different degrees, although only 10-15% of the population is affected 
from severe forms. 
The tooth supporting structures may be lost with different progression rates, depending on 
individual susceptibility, and may lead to edentulism early in life. 
If diagnosed on time, treatment is able to reduce the clinical signs and the microbiological biofilm 
related  to the disease.  
Traditionally the first step of periodontitis treatment aims to disrupt the sub-gingival biofilm and to 
re-establish a healthier microbiological environment. This is commonly done by a combined 
manual and power-driven (ultrasonic or piezo-electric) debridement of the pocket by scaling and 
root-planing (SRP) associated with effective supra-gingival plaque control.  
Periodontal indices that are associated with periodontitis are the increase of probing pocket depth 
(PPD), loss of clinical attachment (CAL) and bleeding on probing (BOP). SRP is able to reduce 
these indices to a certain degree although changes following treatment may be less acceptable by 
the patients, mainly the recession of the gingival margin (REC) and the increase in dentinal 
hypersensitivity (SEN). 
Recently an air-abrasive system for supra- and sub-gingival  debridement has been introduced, for 
the treatment of periodontally affected teeth. 
 
1.2  Background information  on  Air-Polishing and Perio-Flow EMS 

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In the past few years indications for the use of the air polishing technology have been expanded 
from supragingival use (airflow) to subgingival air polishing (perioflow) by the development of 
new low-abrasive glycine-based powders (GPAP) and devices with a subgingival nozzle. Several 
studied on the subgingival use of air polishing have been completed. During the Europerio 7 
Congress in Vienna a consensus conference on mechanical biofilm management took place aiming 
to review the current evidence from the literature on the clinical relevance of the subgingival use of 
air polishing and to make practical recommendations for the clinicians. (Sculean et al. 2013). 
The latest development of a specially designed nozzle for subgingival air-polishing devices led to a 
reduction of the working pressure along with an air jet directed perpendicularly to the root surface. 
Since none of the published studies reported any adverse events related to the use of subgingival 
air- polishing devices, it was suggested that for the removal of supra- and subgingival dental 
biofilms this treatment regime may be superior to hand instrumentation, particularly with respect to 
patient comfort, dental hard tissue loss, and time efficiency. Recently, a new low abrasive erythritol 
powder (EPAP) with comparable physical properties to GPAP was introduced for subgingival air 
polishing. Erythritol, a non-toxic, chemically neutral, and completely water- soluble polyol is 
widely used as an artificial sweetener and as a food additive. Due to its comparable particle size to 
that of glycine and its promising chemical characteristics allowing the binding of antiseptic sub- 
stances, it was recently suggested to be suitable for subgingival biofilm removal. Additionally, 
recently published data demonstrated an inhibitory effect of erythritol to some 
periodontopathogenic bacteria such as Porphyromonas gingivalis. Very recent data indicate that 
subgingival air polishing with EPAP resulted in short-term clinical outcomes comparable to SRP. 
Moreover, the use of EPAP yielded superior outcomes to hand instrumentation in terms of patient 
comfort and time efficiency. 
 
 

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1.3 Rationale for clinical study of Air-Polishing and Perio-Flow for the treatment of 
periodontitis. 
So far the first treatment of severe generalized periodontitis is based on the biofilm removal, 
from the dental roots in the supra- and the sub-gingival environment, with the use of power-
driven and hand instrumentation. This instrumentation, although proven to be successful, 
leads to substantial discomfort to the patients and to unpleasant gingival recessions. It is, 
therefore, of utmost importance to develop methods optimized for therapy with the aim to 
reduce these problems and to maintain the same successful healing as with previously 
described instrumentation. 
 
1.4 Study design  
This will be a prospective, single-masked, randomized clinical trial.   
 
1.5 Study period   
01.01.2017-31.12.2018 
 
1.6 Study setting  
This will be a prospective, single-masked, randomized, split-mouth clinical trial.  
The study will follow the Consort Statement and be registered in the Clinical Trials Registry. 
Study setting will be the clinical periodontal clinic of the University of Brescia. Patient screening, 
inclusions and all clinical examinations will be performed by one specialist in periodontology (MM 
– Principal Investigator), while treatments will be performed by one DDS (ES) other than the 
dedicated examiner. 
 
 

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1.7 Patients: 
32 patients diagnosed with severe generalized periodontitis will be included.  
 
1.8 Main Inclusion criteria:   
Age: 30-75 with diagnosis of severe generalized periodontitis.  
Systemically healthy. 
At least 5 teeth per quadrant and a minimum of 4 sites per quadrant with PPD ≥ 5 mm and loss of 
CAL ≥ 3mm. 
Sites with PPD ≥ 10 mm will be excluded from measurement 
 
1.9 Main Exclusion criteria:  
Severe Smoking more than 10 cigarettes per day 
Pregnancy or nursing. 
Radiotherapy. 
Chemotherapy. 
BPCO, asma 
Systemic long-term corticosteroid treatment. 
AB treatment in the period of 3 months before the start of the study.  
Non surgical therapy in the period of 3 months before the start of the study 
 
1.10 Preoperative evaluation:  
Clinical and radiographic evaluation including periodontal and dental status.  

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The radiographic evaluation includes intra oral radiography.  
Clinical screening includes routine history and physical examination. 
Admission criteria. 
Signed informed consent. 
 
1.11 Treatment procedure:  
Quadrants I&IV and II&III will be randomly treated either by ultrasonic instrumentation followed 
by root-planing with mini curettes or by ultrasonic instrumentation and air-abrasive treatment FM-
EPAPT.  
Follow up every 3 months 
 
 
1.12 Main outcome measures:  
Baseline, 6, 12, 24, 52 weeks after initial treatment: 
Change in tissue inflammation (Bleeding on probing (BoP). 
Pocket probing depth (PPD). 
Recession of the gingival margin (REC). 
Clinical Attachment Level (CAL). 
Plaque Index (PI). 
Tooth Hypersensitivity Test (Schiff Index). 
Changes in composition of the subgingival microbial biofilm. 
 
 
1.13 Adverse event evaluation and reporting:  
Adverse events by open questioning and by completing a written questionnaire. Any serious 
adverse event, injury or negative effect, death or life-threatening event must be reported within 24 
hours to the ethical committee. 
 

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2. 
HYPOTHESIS AND STUDY OBJECTIVES 
 
2.1  Null hypothesis and alternate hypothesis 
2.1.1 H0:  
There will be no significant difference in reduction in parameters of periodontitis after debridement 
with Ultrasonic and Air-abrasive (Test treatment) instrumentation neither 6 weeks, 12 weeks and 24 
weeks  post therapy as compared with baseline. 
There will be a significant difference in reduction in parameters of periodontitis after Test treatment 
at 6 weeks, 12 weeks and 24 weeks post therapy in favour of Control treatment. 
 
2.1.1 HA:  
There will be a significant difference in reduction in parameters of periodontitis after debridement 
with Ultrasonic and Air-abrasive (Test treatment) instrumentation neither 6 weeks, 12 weeks and 24 
weeks  post therapy as compared with baseline. 
There will be no significant difference in reduction in parameters of periodontitis after Test 
treatment Tr 6 weeks, 12 weeks and 24 weeks post therapy as compared with Control treatment. 
 
2.2 
Primary Objective  
To assess the clinical efficacy of Ultrasonic and Air-abrasive (Test treatment) instrumentation used 
as root debridement for treatment of severe generalized periodontitis. Primary end-point is  pocket 
closure (PPD ≤ 4mm). 
 
2.3 
Secondary Objectives 
To assess other clinical indices measured for periodontitis (REC,CAL, BOP, PI; Schiff Index). 
To assess the changes in the sub-gingival microbial biofilm after treatment. 

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To assess the time spent by the therapist in treatment. 
To assess patient subjective appraisal of morbidity (i.e., pain) and preference of both treatments 
used (VAS scale).  
To assess safety of treatment by evaluating the occurrence of adverse events 
 
 
 
3 
Interventions 
 
3.1  
Treatment procedure 
The initial debridement is performed with local anesthesia as needed. Randomly assigned quadrants 
will be treated by FM-EPAPT or SRP. 
Maintenance procedure will be performed at 12, 24 and 36 weeks. Each quadrant in both active 
treatment groups, will be randomly maintained by either a FM-EPAPT procedure or by ultrasonic 
debridement.    
 
3.2 
Examinations 
Clinical examinations are to be made six weeks, at 12, 24, 36 and 52 weeks after initial therapy  
(i.e. the terminal evaluation is performed 12 months after initial (baseline) therapy and 9 months 
after the maintenance therapy). 
PPD, REC, CAL, BOP,  will be recorded at 6 sites (mesio-buccaly, buccaly, disto-buccaly, disto-
palataly, palataly, mesio-palataly) around each  tooth using a UNC- PCP 15 periodontal probe (Hu-
Friedy), rounding up the measure at the nearest millimeter. Bleeding on probing is assessed at all 
teeth (6 sites/tooth) using dichotomous scoring within 30 seconds following probing of the pocket. 
Plaque for the full dentition, will also be assessed using dichotomous scoring. Radiographs will be 
taken at baseline and at 6 months after therapy. 
Microbiological samples will be collected from the 2 deepest pockets in each quadrant with sterile 

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size 40 paper points and pooled in a transferring vial (4 samples/patient/examination). Sites to be 
collected will be isolated with cotton rolls. Supra-gingival plaque from the tooth surface will be 
removed with sterile curettes and thereafter air-dried. A n°40 sterile paper-point will be inserted in 
the depth of the pocket and removed after 10 sec, both from the vestibular and from the palatal side. 
Samples will be transferred into a sterile eppendorf containing suitable transport fluid and then 
transported to the microbiological laboratory for processing. 
 
4 
STUDY METHODS 
 
4.1 
INCLUSION CRITERIA 
 
 
 
In addition to general medical condition and history, patients can be included if they meet the 
following conditions: 
 
1. Age: 30-75 with diagnosis of severe generalized periodontitis.  
2. At least 5 teeth per quadrant and a minimum of 6 sites per quadrant with PPD ≥ 5 mm 
and loss of CAL ≥ 3mm. (Sites with PPD ≥ 10 mm will be excluded from measurement 
but not from treatment). 
3. Eligible for treatment in an outpatient dental clinic (ie, ASA I and II). 
4. Signed Informed Consent obtained prior to start. 
5. Psychological appropriateness. 
6. Consent to complete all follow-up visits. 
 
4.2      EXCLUSION CRITERIA 
 
In addition to general conditions and history, patients should be excluded if they meet any of the 

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following conditions: 
 
1. Was receiving medications known to induce gingival hyperplasia. 
2. Had uncontrolled diabetes (HbA1c > 6.5). 
3. Was receiving systemic antibiotics < 3 months prior to intervention. 
4. Were pregnant or lactating. 
5. Any condition or current treatment for any condition, which in the opinion of the 
investigator and/or consulting physician, may constitute an unwarranted therapeutical 
risk. 
6. Presence of psychological characteristics such as inappropriate attitude or motivation 
which, in the opinion of the investigator, are incompatible with the risks involved with 
the treatment. 
7. Unwillingness to undergo treatment 
8. Ongoing or previous radiotherapy to the head-neck region 
9. Ongoing or previous chemotherapy 
10. Systemic long-term corticosteroid treatment  
11. Patients taking anticoagulants 
12. Heavy smokers more then 10 cigarettes per day 
 
4.3 
WITHDRAWAL CRITERIA 
A patient will be discontinued from the study under the following circumstances: 
 
1. Progression in bone loss at teeth or other complication such as pronounced 
inflammation more than at study start (i.e., puss or abscesses). 
2. Change in status with respect inclusion/ exclusion criteria such as pregnancy or 
psychological illness. 

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3. Intake of antibiotic medications or any local antiseptics during the length of the clinical 
trial. 
 
 
 
4.4 
Schedule of investigational procedures 
 
 
The investigational procedures are given in Table 1.  
 
Table1.  See attached file ERISRP CHART - Investigational procedures before, during and 
after therapy.  
 
 
 
 
 
 
 
4.5 
Clinical study procedures 
PREOPERATIVE PROCEDURES  
Routine history and physical examination will be performed and information recorded on the 
Preoperative Patient History Record. The therapist may use his/her customary history and physical 
procedures; however all data specified on the Preoperative Patient History Record must be recorded 
on the form. Exclusion Criteria are also included on the form. Entries checked YES will exclude 
patients from admission into the study. 
 
4.6 
PREOPERATIVE PROCEDURES 
Treatment approach and technique will be carried out according to a standardized procedure. 

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Collection of clinical indices involved in the study by the principal investigator (MM) who will be 
always unaware of which quadrants  have been treated with the test procedure. 
Clinical operator (ES) opens a sealed envelope containing randomization allocation that assigns 
which of  the group of quadrants I&IV or II&III quadrants to treat with test and control treatments. 
Treatment of the quadrants will always start with the group of quadrants I&IV.  
Treatment of the assigned group of quadrants with the assigned test or control treatment under local 
anesthesia.  
Clinical operator takes note of treatment time/number of teeth 
Patient is instructed again on proper personal oral hygiene procedures. 
Self evaluation questionnaire is given to the patient. 
DAY 2: 
The clinical operator treats the remaining two quadrant with the remaining treatment (test or 
control). 
Clinical operator takes note of treatment time/number of teeth 
Patient is instructed again on proper personal oral hygiene procedures. 
Self evaluation questionnaire is given to the patient. 
 
4.7 
CONTROL TREATMENT 
Under local anesthesia supra- and sub-gingival scaling and root planing, of the two selected 
quadrants (by randomization) will be performed with the use of piezo-electric instrumentation 
(EMS  Piezon Master) and hand instrumentation by using mini curettes. The clinical operator 
annotates the time spent per quadrant/number of teeth and per quadrant/sum of mm of pocket depth, 
but has no limitation of treatment time. 
4.8 
TEST TREATMENT 
The two quadrants treated or remaining to be treated will be covered with a Teflon membrane to 
avoid a cross-over effect of the air-abrasive powder used. Disclosing plaque. Under local anesthesia 

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the gingiva and the oral mucosa are decontaminated with the Air-flow device with an Erythritol 
based powder. The supra-gingival hand-piece is used with a power of 50% and maximum irrigation. 
The supra-gingival biofilm is removed using the same tool and the same setting, directing the hand-
piece with a 45° degree angle towards the coronal part. Each site is decontaminated for 5 seconds. 
The gingival crevices and the most coronal part of the pockets is then decontaminated by directing 
the hand-piece towards the gingival margin with a 45°angle, again for 5 seconds at each site. 
For the pockets deeper than 5 mm, the Perio-flow hand-piece is used with the flexible nozzle 
attached in Perio modality setting with a 50% power and maximum irrigation. The nozzle is 
inserted in the depth of the pocket and then moved coronally and mesio-distally in order to 
decontaminate the root surface as much as possible. This was repeated at each of the 6 sites for 5 
seconds using the same powder as for the supra-gingival part. 
Thereafter, supra- and sub-gingival debridement e calculus removal is performed using a piezo-
electric deviceǁ with a PS-P-PL3-PL4-PL5 tips. The tool is set with a power of 70% and an 
irrigation of 100%, and discontinued when the surface is judged as clean. 
The clinical operator annotates the time spent per quadrant/number of teeth and per quadrant/sum of 
mm of pocket depth, but has no limitation of treatment time. 
 
4.9 
POSTOPERATIVE FOLLOW-UP PROCEDURES  
 
All postoperative evaluations will be recorded on the Postoperative Report Form 6, 12, 24, 36 and 
52 weeks post therapy. Furthermore radiographs will be taken after 12 months to exclude 
progression in bone loss. 
At the 12, weeks recall Each quadrant in both active treatment groups, will be randomly maintained 
by either a FM-EPAPT procedure or by ultrasonic debridement.    
Clinical complications such as infection, pain, etc. will be recorded during all postoperative follow-
up visits, should they occur.  

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4.10     DATA COLLECTION STUDY REPORT FORM – COMPLETION SCHEDULE 
 
The schedule for the completion of the various forms and report forms is provided in Table 2.  
Table 2: Data Collection / Report Form Completion Schedule 
 
Form Name 
Completion Schedule 
Preoperative Patient History 
Record  
Prior to the study procedure 
Informed Consent Form 
Prior to the study procedure 
Baseline report 
Immediately prior to treatment 
Treatment Report 
Immediately following procedure 
Postoperative Report 
Immediately at 6 weeks , 12 and 24 
weeks  
Adverse Event Reporting 
Immediately following event 
 
 
 
 
5.13 
 
Case Report Forms 
 
 
Case Report Forms (CRFs) of a design mutually agreed upon by the Investigators. A CRF is 
required and should be completed for each included patient, and signed. Corrections of data should 
be made using a single line, leaving the corrected data clearly visible. The accurate data should be 
entered next to the inaccurate data. All changes should be initialled and dated by the Investigator. If 

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corrections are performed by another member of the staff, the Investigator has to approve the 
correction.  
 
 
 
6. 
Adverse events    
 
 
An Adverse Event (AE) is any untoward medical occurrence in a patient during a clinical 
study, whether or not considered to be related to the investigational therapy. An AE can therefore 
be any unfavorable or unexpected sign (including abnormal laboratory findings), symptom, or 
disease which develops or worsens in intensity during the course of the study, whether or not 
related to the investigational therapy. 
 
 
 
AE also include accidents, reason for medical consultation, reason for admission to hospital, 
and reason for surgical operation. However, any hospital admission or surgical operation for illness 
or disease that existed before the patient was enrolled in the study, and did not worsen during the 
study, is not to be reported as AE. 
   
 
 
Clinical Investigators must report any serious adverse reaction, injury or effect, death or life-
threatening occurrence that may be reasonably suspected of being associated with the treatment to 
the Ethics Committee. All other complications, device related or otherwise, occurring to any patient 
in the course of this investigation must be recorded. 
 
6. 
PATIENT INFORMATION AND CONSENT 
 
See attached model 
 
 
7. 
STATISTICAL ANALYSIS 
 
Data will be analyzed both at patient level focusing on a within patient difference between two 

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proportions (proportion of PPD ≤ 4mm in the two treatments) as well as considering the response at 
site level fitting a GLMM model with binomial link function and multilevel structure matching the 
design. 
 
  
7.1.      SAMPLE SIZE 
Sample size for primary outcome (proportion of PPD<4mm) was computed through simulation 
assuming a non-inferiority trial with 2x2 crossover design for proportions. Data were simulated 
(B=1000 simulations) assuming  three random intercepts (subject, tooth and site) and a within 
subject random slope (the within subject treatment effect). Variance estimates for the random 
effects were computed from existing data on a similar setting.  Assuming a significance level of 
5%, a tolerance margin of 10% a sample size of N=32 subjects will provide a 80% power. 
Considering  potential drop outs after phase I randomization to treatment phase (phase I) and 
maintenance phase (phase II) will be performed in a two step procedure. Subjects will be 
randomized to a AB scheme with varying sequence of treatment administration to the two split-
mouth areas (or  maintenance therapy). The seed used for randomization is 2640. 
 
 
 
7.2.     STATISTICAL EVALUATION