Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03548896 |
| Other study ID # |
PER 2016-02 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 2016 |
| Est. completion date |
July 2019 |
Study information
| Verified date |
July 2018 |
| Source |
Universitat Internacional de Catalunya |
| Contact |
DIZ |
| Phone |
+34 630793155 |
| Email |
PEDRODIZIGLESIAS[@]GMAIL.COM |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
There is limited data regarding socket preservation in three wall defects and no enough
evidence of implant placement in previously regenerated area with allograft.
The aim of this randomized controlled clinical trial is to analyze and compare dimensional
changes in extractions sites with buccal bone defects > 5 mm left untreated (simultaneous
regeneration during implant placement) or treated using a mineralized allograft.
Description:
1. Introduction:
The alveolar process is tooth dependent and once a single tooth is extracted, the
architecture of the socket undergoes dimensional changes hindering the prosthetic
rehabilitation at the edentulous crest which demands a posterior guided bone
regeneration (GBR). Studies in dogs described the main changes happened after tooth
extraction (1,2); the blood forms a clot at the wound site which is replaced by a
connective tissue matrix: after 1 month the woven bone fills the extraction socket;
subsequently the woven bone undergoes osteoclastic resorption which leads to a
maturation of the recently formed bone, gradually replaced with lamellar and bone
marrow. Such events were clinically evaluated in several studies with an average of loss
in width (3.5-4mm) (3). Bone resorption in height is correlated to the plate thickness;
thin-wall phenotypes (<1mm) have a median vertical bone loss of 7.5mm in the central
risk zone (4). Moreover, at the aesthetic zone, this narrow crest makes more difficult
the adequate implant placement (5), then functional and esthetic complications can be
expected.
The fresh socket in the esthetic zone represents a challenge for the clinician and
immediate implant placement (type I) is associated with a high risk of mucosal
recessions. Moreover, the absence of the buccal plate increases the risk (6). Early
implant placement (type II) described by Buser et al. (7) reported long term excellent
esthetic results and this technique is compatible with alveolar ridge preservation.
Alveolar ridge preservation is a widely used technique immediately after tooth
extraction to minimize the alveolar resorption, to accelerate the bone formation and to
improve the prosthetic restoration with an implant placed on a tridimensional way.
Different biomaterials were used: autografts (8), allografts (9), xenografts (10,11),
alloplasts (11,12) with or without barrier membranes. In all of them, less bone
resorption was drawn with respect to natural healing; however, such techniques do not
prevent physiologic bone resorption but limit it, improving the expected results in
absence of preservation (13). Comparing the healing time with different biomaterials,
mineralized bone allograft demonstrated similar results in the amount of new bone growth
at 3 and 6 months after extraction (14) allowing the reentry before.
In many cases, it is reported the absence of the buccal bone plate after tooth
extraction; according to Chappuis et al. 2013 (4), at the anterior maxilla, central wall
thickness has less than 1 mm in approximately 69% of the cases, increasing the risk of a
resorption after healed or even it may disappear after tooth extraction due to the lack
of consistency which affects aesthetics negatively.
The bone remodeling not only happens among the three first millimeters (mm) as
previously reported (2) and a primate model clearly demonstrated that the bone
remodeling was not limited to the crestal 3-mm zone and extended up to 6 mm below the
alveolar crest, where a mean volumetric bone loss of 30% and 45% at 6 and 12 weeks in
intact sockets while more pronounced bone loss with 60 and 86% volumetric bone loss in
the 0-3 mm zone, respectively, in the untreated dehiscence group and the use of
biomaterials in combination with a membrane reduces the volumetric bone loss up to 25%
(15).
There is limited data regarding the effect of ridge preservation in 3 bone wall defects
sockets. Some studies allowed partial bone wall (16-19), while only five studies have
investigated the effect of alveolar ridge preservation on buccal wall defects (20-23).
Alloplastic materials have evidenced adequate outcomes regarding ridge width maintenance
requiring posterior guided bone regeneration at the implant surgery in a
few cases (27,8%) (24) or no regeneration at two months post preservation (22).
2. Background:
Dehiscence-type defect associated with the extraction socket still presents a problem if
an implant is desired in such site. Recently published study has reported the necessity
of posterior guided bone regeneration at the reentry for implant placement in 50%
previously preserved ridges when using xenograft (23). No data regarding the effect on
ridge preservation dehiscences is available using a mineralized allograft and membrane,
and if it has benefits compared to the conventional guided bone regeneration at the
implant placement.
A recent systematic review recommends further research on ridge preservation assessing
the integrity/absence of the buccal plate in the dimensional changes and long term
evaluation of bone levels after implant placed in alveolar sockets previously treated
with alveolar ridge preservation using standardized radiographs taken at specific period
of times (25). Furthermore, the soft tissue volume stability is of great importance in a
esthetic high risk zone (26) which was not reported in any previous study. Therefore,
the aim of this randomized controlled clinical trial is to analyze and compare
dimensional changes in extractions sites with buccal bone defects more than 5 mm left
untreated or treated using a mineralized allograft.
3. Objectives:
3.1 General objective
To compare the dimensional changes in bone and soft tissues happened after tooth
extraction in alveolus with dehiscences when using a mineral allograft and resorbable
membrane (test group) or natural healing (control group) at 3 months.
3.2 Specific objectives
3.2.1 To compare bone changes in width and height from the baseline (immediately after
tooth extraction) to the implant placement stage at 3 months, and at 12 months after
tooth extraction between test and control groups.
3.2.2 To compare marginal bone loss around implants, from the baseline (time of implant
placement) to the second-stage surgery, at the prosthetic loading, and at 12 months
after tooth extraction between test and control groups.
3.2.3 To compare the facial soft tissue level at the baseline (immediately before tooth
extraction) and at 3 months, at the second stage implant surgery, at the prosthetic
loading, and at 12 months after tooth extraction between test and control groups.
3.2.4 To compare volumetric changes at baseline, at 3 months (previous implant
placement), at the second stage implant surgery, at the prosthetic loading, and at 12
months after tooth extraction between test and control groups.
3.2.5 To compare the width of keratinized tissue at the baseline, at 3 months, before
the second implant surgery, at the prosthetic loading, and at 12 months after tooth
extraction between test and control groups.
3.2.6 To compare the pink esthetic score at the end of the evaluation between test and
control group.
4. Hypothesis:
4.1 Null hypothesis
- Ho1. Dimensional changes are greater in the test group than in the control group.
- Ho2. Bone changes in width and height are greater in the test group than in the
control group.
- Ho3. Marginal bone loss around implants are greater in the test group than in the
control group.
- Ho4. The facial soft tissue level is worse maintained in the test group than in the
control group.
- Ho5. There are more volumetric changes in the soft tissues in the test group than
in the control group.
- H06. The width of the keratinized tissue is lower in the test group than in the
control group.
- H07. The pink esthetic score is fewer in the test group than in the control group.
4.2 Alternative hypothesis
- H11. Dimensional changes are lower in the test group than in the control group.
- H12. Bone changes in width and height are lower in the test group than in the
control group.
- H13. Marginal bone loss around implants are greater in the test group than in the
control group.
- H14. The facial soft tissue level is better maintained in the test group than in
the control group.
- H15. There are less volumetric changes in the test group than in the control group.
- H16. The width of the keratinized tissue is greater in the test group than in the
control group.
- H17. The pink esthetic score is higher in the test group than in the control group.
5. Material AND Methods:
5.1 Study design
This is a randomized controlled clinical trial with a 1-year follow-up. The recruitment
of the patients will start on February 2016
5.2 Setting of the study
The study will be performed at the Universitat Internacional de Catalunya (UIC).
Subjects will be recruited consecutively from the Department of Periodontology.
5.3 Study population
Patients referred to Department of Periodontology for treatment of periodontal diseases
and who meet the inclusion criteria will be included in the study. Those with
periodontal disease will be included in the study after periodontal treatment. Patients
will be recruited consecutively. Furthermore, all study subjects will provide written
informed consent before participating in the study. The study will be performed
following the principles outlined in the Declaration of Helsinki (revised, amended, and
clarified in 2013).
5.4 Study procedures
5.4.1 Screening examination
Two calibrated investigators will evaluate and enroll the patients (P.D. and C.V.).
The clinicians will review with the patient the Information and Medication History Forms
and record the information. Patients will also be advised of their role in this study
and asked to sign an informed consent. No patient will be admitted to the study until
the
informed consent form is signed. After giving consent, patients will undergo an oral
pathology examination. After completion of the oral pathology exam, patients will
undergo a full-mouth manual probing using a periodontal probe PCP-UNC 15 (HuFriedy,
Rockwell St, Chicago, IL) to determine their periodontal status and, if needed, a
full-mouth periapical radiographic examination.
To take part in this study, one maxillary anterior tooth (from second premolar to second
premolar) must show an absence of > 5mm of the buccal plate, measured with the
periodontal probe PCP-UNC 15 (HuFriedy, Rockwell St, Chicago, IL) from the theoretical
position of the alveolar crest.
5.4.2 Study groups
Patients will be randomly assigned to Test (n=14) or Control (n=14) groups using opaque
envelopes after obtaining an automatic randomization list (generated with a software).
- Control group (CG): after tooth extraction, a blood clot will be allowed to form in
the alveolar defect. Augmentation of the buccal wall will be performed following
socket healing, at the time of implant placement.
- Test group (TG): after tooth extraction, the alveolar defect will be treated with
mineralized allograft in combination with a resorbable collagen membrane.
5.4.3 Therapeutic stages
5.4.3.1 First part of the treatment protocol (alveolar ridge preservation OR natural
healing of the socket)
A) Hygienic phase
All patients will receive presurgical therapy, which included oral hygiene instructions,
a session of prophylaxis, and any periodontal treatment necessary to provide an oral
environment more favorable to wound healing.
B) Surgical phase
B.1) Tooth extraction (T0)
After initial therapy, the patient will be scheduled for tooth extraction. Surgical
procedure will be carried out by second and third year residents of the Master of
Periodontology and supervised by the same clinical instructor (C.V.). An alginate
impression will be taken before the surgical procedure as baseline to measure the
volumetric changes.
Prior to the tooth extraction, patients will be instructed to rinse with 0.12%
clorhexidine gluconate for 1 minute before induction of local anaesthesia (40 mgr.
articaine, 0,01ml epinephrine). Pre-surgical medications will not be provided.
Regarding the tooth extraction, all patients will be treated with the same surgical
technique. The teeth will be extracted using a flapless, minimally invasive technique. A
periodontal probe PCP-UNC 15 (HuFriedy, Rockwell St, Chicago, IL) will be used to
measure the vertical distance (VD) between the buccal gingival margin and the bone wall.
Periotomes will be used around each single tooth in order to prevent damage or full
fracture of the facial bone wall. The extraction socket will be thoroughly curetted and
irrigated with sterile saline solution.
After extraction, all patients will undergo CT imaging (cone-beam computed tomography,
CBCT). This will be used as baseline to measure the bone profile. All CT examinations
will be carried out using the same cone-beam instrument. Afterwards, the randomization
envelope will be opened and the sites will be allocated to test (regenerative procedure)
or control (natural healing) groups.
Subsequently, in the test group, extraction sockets will be filled with a mineralized
allograft (OSTEOpureTM) placed, layer-by-layer, gently pressed to the extraction socket.
A trimmed collagen membrane (Ossix Plus, Datum Dental) will be
used to completely cover the socket; thus, extending 2-3 mm onto the alveolar defect
without any further fixation. The soft tissues will be only undermined, and no
releasing incisions will be performed. The collagen membrane will be left intentionally
exposed to the oral cavity. On the contrary, in the control group, the post extraction
alveolus will be filled with a collagen sponge (Octocolagen). Single interrupted
non-resorbable polytetrafluoroethylene (PTFE) monofilament sutures (4-0 Cytoplast;
Osteogenics Biomedical INC., Lubbock, TX, USA) will be used in both groups. Finally, a
custom-
made provisional fixed partial denture without tooth preparation of the adjacent teeth
(FPD) included an ovate pontic to stabilize the graft material (in the test group) and
support buccal soft tissues.
Due to the nature of the study design, neither the patient nor the surgeon will be
blinded.
B.1.1) Post-surgical instructions
Post-surgical instructions will be given to patients. A normal oral hygiene will be
performed except in the surgical area, which will not be brushed until the suture is
removed. After surgery, in the test group, amoxicillin 500 mg every 8 hours will be
prescribed for the following 7 days (clindamycin 300 mg every 6 hours will be prescribed
to penicillin-allergic patients). In order to control discomfort and swelling,
non-steroidal anti-inflammatory treatment (600 mg ibuprofen every 8 hours for 4 days)
will be administered to both groups. Ice packs will be used for 24 h and all subjects
will be prescribed 0.12% chlorhexidine mouthrinse twice daily for 14 days for chemical
plaque control.
B.1.2) Evaluation visits
After a healing period of 14 days, sutures will be removed. Patients will be observed
monthly to control adequate tissue healing and after a 3-month healing period will be
scheduled for re-entry and implant placement. A second alginate impression will be taken
before implant placement for the volumetric analysis. A CBCT scan will be obtained
before implant installation for treatment planning.
5.4.3.2 Second part of the treatment protocol (implant placement and prosthetic
rehabilitation)
A) Implant placement (T1)
Following the application of local anaesthesia (40 mgr. articaine, 0,01ml epinephrine),
a crestal incision will be performed. Implant placement will be performed by second and
third year residents and supervised by the same clinical instructor (J.N.). Buccal and
lingual mucoperiosteal flaps will be carefully reflected and any soft tissue will be
removed. Osteotomies will be prepared and dental implants will be placed according to
manufacturer's recommendations in a prosthetically ideal position. After implant
placement, the presence of a peri-implant bone defect will be evaluated; augmentation
procedures will be considered necessary to treat the residual peri-implant bone defect.
The regenerative procedure will be performed with the use of mineralized allograft
(OSTEOpureTM) covered by a collagen membrane (Ossix Plus, Datum
Dental). Periosteal releasing incisions will be made to the surgical sites to allow for
tension-free coronal advancement of the flaps with complete closure of the sites. After
closure screw insertion, the incisions will be carefully closed with horizontal mattress
sutures as well as single interrupted non-resorbable polytetrafluoroethylene (PTFE)
monofilament sutures (4-0 Cytoplast; Osteogenics Biomedical INC., Lubbock, TX, USA).
Patients will receive the same drug regime as prescribed after the first surgical phase
(i.e. regenerative procedure after tooth extraction). An intra-oral periapical
radiograph will be taken with a long cone paralleling technique (7mA-60kV/20ms). A
radiographic bite block will be used in order to provide reproducible measurements at
each examination time point. The temporary prosthetic restoration used at the first
surgical step will be applied.
B) Second-stage surgery and subepithelial connective tissue graft (T2)
Four months after implant placement, a second-stage implant surgery will be performed.
An alginate impression will be taken before the surgical procedure for the volumetric
analysis. Under infiltrative local anesthesia, a midcrestal incision will be made to the
dental implant region and the mucosa will be raised with a tunneling instrument until
the cover screw is reached. After removing the cover screws, healing abutments will be
placed. A subepithelial connective tissue graft (SCTG)
from the tuberosity will be obtained. A double incision using double-bladed knife
separated by 1.5 mm will be made from the distal of the terminal tooth. A second
incision joining the first one will be made perpendicular at a distal part. The donor
area will be
sutured and the SCTG will be de-epithelized and the required dimensions (10mm height,
12mm length, and 1.5mm thick) checked. Finally, the SCTG will be placed under the flap
and stabilized with resorbable sutures. The buccal flap will be mobilized and wound
closure will be achieved with a non-resorbable suture. The postoperative regimen and
medication will be the same as after the implantation but no antibiotics will be
administered. An intra-oral periapical radiograph will be taken and two weeks later the
sutures will be removed.
C) Prosthetic loading (T3)
After 6 weeks of second-stage surgery, a fourth alginate impression will be taken before
starting the prosthetic restoration. At the end of this stage (T3), a periapical
radiograph will be taken. Patients will be subsequently enrolled onto an oral hygiene
program with a recall visit every 3 months.
D) Follow-up (T4)
The patients will be followed up for 1 year after tooth extraction and a CBCT and a
periapical radiograph will be performed to assess the buccolingual width changes and the
interproximal marginal bone loss, respectively, in each group. Furthermore, the pink
esthetic score (PES) according to Fürhauser et al. (26) will be assessed by the same
calibrated examiner (C.V.). Finally, a fifth alginate impression and a CBCT scan will be
taken at the end of the follow-up period.
5.5 Data collection
A guidebook will be prepared to standardize procedures throughout the protocol, step by
step, for all questionnaires and evidence collection. The data will be transferred to a
computerized database.
5.5.1 Anthropometric and sociodemographic data
An interview will be conducted to obtain information regarding age, race, gender,
medical history, medication, and health behaviour (smoking habits). Smoking behaviour
will be specified as 3 categories: never smoker, former smoker,
or current smoker (light smokers: < 10 cigarettes/day). Patients will be asked about
their tobacco smoke exposure in terms of consumption (i.e. the number of cigarettes
consumed per day); duration (i.e. the number of years of smoking); and life-time
exposure (i.e. the accumulated exposure as formed by the product of consumption and
duration: cigarette-years). In case of former smokers, patients will be asked about the
smoke-free time following cessation.
5.5.2 Clinical parameters
The following clinical parameters will be evaluated by one examiner (P.D.) using a
manual periodontal probe PCP-UNC 15 (HuFriedy, Rockwell St, Chicago, IL) rounded to the
nearest 0.5 mm.
- Visible plaque index (VPI) (28) will be recorded at six sites per tooth (excluding
third molars) at baseline (T0) and at T1, T2, T3, and T4 using a 0-1 measure, where
0 indicates no visible plaque and 1 the presence of dental plaque. The number of
positive sites will be recorded and then expressed as a percentage of the numbers
of sites examined (full-mouth plaque score).
- Modified Plaque Index (mPlI) (29) will be recorded at four aspects (mesial, distal,
buccal, and lingual) around each implant at T3 and T4:
- Score 0: No detection of plaque
- Score 1: Plaque only recognized by running a probe across the smooth marginal
surface of the implant. Implants covered by titanium spray in this area always
score 1.
- Score 2: Plaque can be seen by the naked eye.
- Score 3: Abundance of soft matter.
- Modified Bleeding Index (mBI) (29)will be recorded at four aspects (mesial, distal,
buccal, and lingual) around each implant at T3 and T4:
- Score 0: No bleeding when a periodontal probe is passed along the mucosal
margin adjacent to the implant.
- Score 1: Isolated bleeding sport visible.
- Score 2: Blood forms a confluent red line on mucosal margin.
- Score 3: Heavy or profuse bleeding.
- Width of keratinized tissue (KT) measured mid-facially from the gingival margin to
the mucogingival junction of the intended extracted tooth (T0) or the
implant-supported restoration (T3 and T4); or, from the top of edentulous crest to
the mucogingival junction of the edentulous area (T1 and T2).
- Facial soft tissue levels (STL) will be evaluated (at baseline (T0), and at T1, T2,
T3, and T4) measuring the distance between level of soft tissues at mid-
facial gingival level and a reference line, which connected the facial soft tissue level
of the adjacent teeth.
- Pink esthetic score (PES) will be evaluated at the end of the evaluation period. The
PES is based in 7 variables: mesial papilla, distal papilla, soft tissue level, soft
tissue contour, alveolar process deficiency, soft tissue color and soft tissue texture.
Each variable will be assessed with a 2-1-0 score with 2 being the best and 0 being the
worst score. The highest possible score reflecting a perfect match of the peri-implant
soft tissue with that of the reference tooth is 14 and the lowest score reflecting a bad
match of the peri-implant soft tissue is 0 (26).
5.5.3 Intra-surgical parameters
After tooth extraction, a periodontal probe PCP-UNC 15 (HuFriedy, Rockwell St, Chicago,
IL) will be used to measure the vertical distance (VD) between the buccal gingival
margin and the bone wall.
5.5.4 Radiographic parameters
A calibrated examiner (P.D.) will evaluate the following radiographic parameters:
Horizontal measurements
CBCT scans will be obtained at the time of tooth extraction (T0) and after 3 months (T1)
(approximately 2 weeks before implant installation for treatment planning) and 12 months
(T4). Width measurements will be performed to compare differences between groups after a
healing period of 3 and 12 months. For each socket, a longitudinal (parallel to the root
cross section) view will be obtained.
According to Sisti et al. (22), the total width (TW) of the buccolingual bone will be
measured at three horizontal lines perpendicular to the long axis of the post-extraction
socket: 1 mm (total coronal width, TW1), 4 mm (total median width, TW4), and 7 mm apical
to the palatal bone crest (total apical width, TW7). On the same lines, palatal bone
wall (PW) will be also measured: coronal palatal width (PW1), median palatal width
(PW4), and apical palatal width (PW7).
Vertical measurements
According to Araújo et al. (2), the VD between the palatal and buccal wall peaks will be
measured in CBCT scans.
Intra-oral periapical radiographs with a bite block will be taken with the long cone
paralleling technique (7mA-60kV/20ms) at T1, T2, T3, and T4 (6 months after implant
placement). A paralleling device and individualized bite blocks (Optosil) will be used
for the standardisation of the X-ray geometry. The marginal bone height (MBL) will be
set as the distance between the reference point and the most apical point of the
marginal bone level. The reference point will be the fixture- abutment interface.
Calibration will be performed using the known thread-pitch distance of the implants.
Previously known values, such as mixture diameter and length, will be used for
calibration when the threads will not be clearly visible on the radiographs. The
digitally obtained X-rays will be transferred into a software program (Image J; NIH,
Bethesda, MD, USA).
CBCT analysis Along the 1 year protocol duration of the present investigation, three
CBCT scan will be needed; At baseline, the first CBCT will be taken immediately
following extraction in order to get accurate images of the ridge status. At 3 months,
and before implant placement, a second CBCT scan will be taken, included in the implant
study and it will be useful to compare with the initial CBCT analysis in both groups.
Last of all, at 1 year follow-up a third CBCT scan will be taken in both groups; In the
control group, it will be useful to make comparisons before and after bone graft over
the implant, and in the test group it will allow to make comparisons with the control
group about the buccal plate status.
5.5.5 Volumetric analysis
Alginate impressions will be taken at the baseline examination (T0), and at T1, T2, T3,
and T4. Dental stone casts will be fabricated immediately after the impressions will be
obtained. Models will be evaluated for the presence of irregularities such as porous
areas, undefined gingival margins, broken cusps, or undefined vestibulum.
The cast models will be optically scanned with a desktop 3D scanner. Baseline and
follow-up STL files of the models will be uploaded to an image analysis software
(Swissmeda Software; Swissmeda AG, Zurich, Switzerland). To match the STL files, three
clear and visible common reference points will be selected. After the selection of these
references, the software automatically superimposed the models using a series of
mathematical algorithms. Linear and volumetric measurements will be performed by a
calibrated evaluator.
Stages of the volumetric analysis
- Test group
- Volume preservation: from T0 to T1
- Volume stability: from T1 to T2
- Volume gain (after SCTG): from T2 to T3
- Volume stability: from T3 to T4
- Control group:
- Volume loss: from T0 to T1
- Volume gain (after regenerative procedure): from T1 to T2
- Volume gain (after SCTG): from T2 to T3
- Volume stability: from T3 to T4
5.5.6 Intra-examiner reproducibility
The intra-examiner reliability will be estimated. The degree of intraobserver agreement
of total width (TW) of the buccolingual bone (mm), measured in CBCT scans, will be
determined with the Interclass Correlation Coefficient (ICC). All measurements will be
taken by one examiner (P.D.).
The examiner will be calibrated as follows, five patients not involved in the study with
a CBCT scan will be recruited and used for calibration. The examiner will record the
total width (TW) of the buccolingual bone (measured at three horizontal lines
perpendicular to the long axis of the ridge: 1 mm, 4 mm, and 7 mm apical to the palatal
bone crest) on two separate occasions 48 hours apart. Cali¬bration will be accepted if
90% of the recordings could be reproduced within a difference ≤ 0.1 mm.
5.6 Outcomes
- Primary outcome: Total width (TW) of the buccolingual bone measured in CBCT scans.
- Secondary outcomes: KT, STL, PES, volumetric soft tissue changes, and radiographic
bone loss.
5.7 Withdrawal of consent
The Patient Information Sheet will clearly state that the patient can withdraw from the
study at any time without prejudice or explanation. Such withdrawal will be documented
in the medical record file. Losses to follow-up are taken into account in the sample
size calculations (12%).
5.8 Sample size calculation
Using the total width (W) of the buccolingual bone as the primary outcome variable, the
sample size was calculated. Power calculation based on the detection of a clinically
significant difference ≥ 3 mm in mean crest-dimension difference between treatment
groups, assuming a standard deviation of 2.5 mm (Schropp et al. 2003), with an alpha
error defined to 0.05 and beta error to 0.20 (power 80%), revealed that 12 subjects in
each treatment group were required. In addition, an estimation that 20% of subjects will
be lost to follow-up has been taken into account.
6. Result analysis:
6.9 Statistical analysis
The study variables will be recorded in a case report form (CRF) specially designed for the
study. Each study patient will be assigned a numerical code comprising a 3-digit patient code
(assigned correlatively as they are included in the study). Only the study investigator will
be able to identify the patient by their code.
At the end of the fieldwork, the data contained in the CRFs will be entered into a database
for data analysis and preparation of the final report.
The socio-demographic and clinical characteristics and other variables of interest of the
patients included in the study will be described. Data will be presented as mean ± SD;
categorical data will be shown as percentage of positive patients.
An analysis will be carried out to determine differences in study outcomes between groups.
Analysis will be based on the ITT (intention to treat) population using the last observation
carried forward (LOCF) approach. The relationship between two qualitative variables will be
calculated using the chi-squared test or Fisher's exact test (if in a given case the
frequency observed is < 5). For ordinal variables, linear regression will be calculated using
Kendall's tau coefficient.
Quantitative variables will be compared using the Student's t-test (< 2 categories), analysis
of variance [ANOVA] (for variables > 2 categories), linear regression test and Scheffé's
multiple comparisons test or U Mann Whitney non-parametric test. The linear relationship
between the quantitative variables will be calculated using Pearson's correlation coefficient
or Spearman's rank correlation test (if the variable is not normally distributed). Changes
vs. baseline will be analyzed using the Wilcoxon non-parametric test or Mc Nemar test.
Level of significance will be set at 0.05. The SPSS version 19.00 software (SPSS Inc.,
Chicago, IL, USA) will be used for all analyses.
