Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04299386 |
| Other study ID # |
CERC-19-084-P |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2023 |
| Est. completion date |
July 1, 2024 |
Study information
| Verified date |
July 2023 |
| Source |
Université de Montréal |
| Contact |
Robert Durand, DMD, MS |
| Phone |
514-343-7464 |
| Email |
robert.durand[@]umontreal.ca |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Dental implants are a well-accepted treatment for replacing missing teeth, due to excellent
patient satisfaction regarding function, aesthetics, and comfort, as well as their long-term
survival. However, the accumulation of bacterial biofilm on implants changes their surface
biocompatibility and initiates peri-implant diseases, such as peri-implant mucositis and
peri-implantitis. Professional cleaning of the implant surface is necessary to remove the
biofilm and facilitate healing within the surrounding tissue. Prophylaxis pastes can be used
in dental clinics to assist the mechanical removal of biofilm by dental professionals.
However, these pastes can contain abrasives that detrimentally affect the surface stability
and chemical properties of the implant surfaces.
ImplanTreat® and Neophylaxis® are novel nanocrystal gels designed for implants' professional
cleaning, under surgical and non-surgical procedures respectively. These products present
high biocompatibility proprieties that can improve peri-implant bone healing. Moreover, they
don't contain abrasives, or fluoride, which preserves the implant surfaces. The researchers
hypothesize that professional implant cleaning with Neophylaxis® or ImplanTreat® results in a
greater reduction of peri-implant inflammation and dental plaque accumulation in comparison
to cleaning without any product. Accordingly, the purpose of this study is to verify if
Neophylaxis® and ImplanTreat® enhance the efficacy of professional cleaning and preserve
implant surface roughness.
The researchers will randomly divide the recruited participant into two groups depending on
the clinical diagnosis, each patient will be either recruited in peri-implant mucositis group
(Group I), or in peri-implantitis group (Group II). Each patient in the group I will be
assigned randomly to receive either implant cleaning with Neophylaxis® or cleaning without.
Similarly, each patient in group II will be assigned randomly to receive either implant
cleaning with ImplanTreat® or cleaning without. No participant will be aware of his
allocation before the end of data collection. In each evaluation session, The researchers
will examine the participants' implants and evaluate the removal of biofilm as well as the
improvement of the peri-implant tissue health and bone level. The researchers will then
analyze and compare the results obtained from each study group.
Description:
Background:
Oral hygiene and regular maintenance are crucial to sustaining healthy peri-implant tissues.
However, current available prophylaxis products and toothpaste tend to contaminate and abrade
the surface of implants, due to the high affinity of humectants, thickeners and surfactants
to the implant surface and the high abrasiveness of silica microparticles used in these
products. Nanocrystalline magnesium phosphate (NMP) gel, a novel inorganic colloidal
suspension, is the result of 7 years of research in Dr. Faleh Tamimi's laboratory in
collaboration with researchers from McGill University. It is a hydrogel with unique
biocompatibility that can improve peri-implant bone healing. The NMP gel forms highly stable
inorganic colloidal suspensions with interesting rheological properties (i.e. thixotropy)
that are ideal for toothpaste and prophylaxis paste applications and do not require the
addition of organic thickeners. The product contains magnesium phosphate (3.02% w/v) and
sodium phosphate (8.23% w/v) in 3 mL syringe.
Hypotheses (null):
Professional cleaning of implant surfaces with NMP prophylactic gel during maintenance visits
will result in similar reductions of gum redness, bleeding and plaque scores after 4 weeks
than implant surfaces cleaned without gel.
Professional cleaning with NMP treatment gel of implant surfaces diagnosed with
peri-implantitis will result in similar reductions of peri-implant probing depth, bleeding,
plaque scores and suppuration after 4 weeks, as well as improved bone levels after 6 months,
compared to implant surfaces, cleaned without gel.
Objectives:
To assess if professional cleaning of dental implants and abutments with signs of mucositis
using NMP gel, during maintenance visits has better outcomes when compared to the cleaning
without gel.
To assess if professional cleaning of dental implants and abutments with the NMP treatment
gel, is more efficient in controlling the infection around implants with peri-implantitis
than cleaning without gel.
Study design: This study will be conducted as a prospective, randomized controlled trial. The
study is categorized as pivotal study and is intended to collect clinical evidence on the
efficacy and safety of the tested product in a statistically justified number of subjects
based on FDA classification of clinical trials for medical devices; it is equivalent to a
Phase 3 clinical trial in the classification scheme for clinical trials of pharma products.
The intervention group will receive the professional dental implant and abutment cleanings
with NMP gel after flap elevation surgery and irrigation (ImplanTreat®, Invicare, Montreal,
Canada), while the control group will receive also flap elevation surgery with irrigation but
without gel application.
The participants' recruitment will take place at the implantology dental clinic of the 3
participating universities: McGill University (Montreal, QC), Université de Montréal
(Montreal, QC), and Harvard University (Boston, US). Potential study participants will be
identified from populations of implant-supported/retained prosthesis wearers: patients with
removable and/or fixed implant- prosthesis who visit the mentioned clinics during the period
of study recruitment. During their visit to the dental clinic, patients will receive an oral,
periodontal and radiographic examination. Intraoral photographs will be taken at baseline for
all the participants to confirm the diagnoses of peri-implantitis. Patients will be invited
to participate in the trial if the oral examination confirms a diagnosis of peri-implantitis,
defined as bleeding/suppuration after probing on at least one peri-implant site (mesiobuccal,
buccal, distobuccal, mesiolingual, lingual, and distolingual aspects), combined with
peri-implant bone loss ≥ 3 mm and probing depth ≥ 6 mm[46], justifying a surgical treatment.
In the case of patients with two or more implants that show peri-implantitis, only one
implant per patient will be randomly allocated into an intervention or control group. All
patients meeting eligibility criteria will meet with the study coordinator and will have to
sign consent forms if they are interested.
To be considered for inclusion in the study, patients should meet the following criteria:
Male or female patients aged 18 years and older. Patients with upper or lower
implant-supported/retained prostheses. The implant should be in function for 12 months or
more. To be included in group I, peri-implant mucositis should be diagnosed. To be included
in group II, peri-implantitis should be diagnosed.
Patients will be excluded from participating in the study if they meet these exclusion
criteria:
Patients who have undergone radiotherapy in the head and neck region, chemotherapy or
systemic long-term corticosteroid treatment; Patients receiving medications known to induce
gingival hyperplasia; Patients who have taken systemic antibiotics less than 3 months prior
to baseline; Patients with prosthetic factors that prevent clinical measurements Implants
with technical complications, such as poor marginal contour or any type of prosthetic
complication that would be a local contributing factor to chronic inflammation.
Peri-implant bone loss > 50% [47] Presence of any acute oral infection. Presence of
uncontrolled diabetes or other systemic diseases. Intravenous bisphosphonates Oral
bisphosphonate intake for more than 3 years. Both cleaning procedures, with and without NMP
gel, will be provided by the same dental professional. Measurements will be performed at
baseline and at follow up visits by a second blinded dental professional. Data will also be
analyzed by a statistician who will be blinded to the intervention assignment. Participants
will also be blinded during the study intervention and follow-up.
A research assistant will be responsible for the coding process and giving the coded data to
the biostatistician. The coding for the trial arms will be withheld from the examiners until
data analysis is complete.
Remove the screw-retained bridge or removable prosthesis. The intervention group will receive
the professional dental implant and abutment cleanings with NMP gels (NeoPhylaxis® or
ImplanTreat®), while the control group will receive the professional dental implant and
abutment cleanings without gel.
Participants will be classified into 2 groups, based on their peri-implant clinical
condition, to separately answer the two main objectives of the trial. Group, I will include
patients with peri-implant mucositis, and group II will include patients with
peri-implantitis. Participants in group I will then be randomized to either NeoPhylaxis® or
control, and participants in group II will be randomized to either ImplanTreat® or control.
The intervention group will receive the professional dental implant and abutment cleanings
with NMP gels (NeoPhylaxis® or ImplanTreat®), while the control group will receive the
professional dental implant and abutment cleanings without gel. Participants will be
classified into 2 groups, based on their peri-implant clinical condition, to separately
answer the two main objectives of the trial. Group, I will include patients with peri-implant
mucositis, and group II will include patients with peri-implantitis. Participants in group I
will then be randomized to either NeoPhylaxis® or control, and participants in group II will
be randomized to either ImplanTreat® or control.
Group I cleaning procedure: For participants allocated to NMP gel only, apply NeoPhylaxis®
gel on the implant/abutment surface and on the rotary brush. For the control group, cleaning
will be done with the rotary brush alone and no gel will be applied. The rotary brush will be
held perpendicularly while gently touching the contaminated implant surface and moving at a
circular motion speed of ~2,500 rpm for ~20 seconds. The surface will be brushed thoroughly
until all visual contaminants are removed, followed by water irrigation to remove
contaminants and any remaining gel.
Group II cleaning procedure: Proceed with local anesthesia, then supra-crestal incision,
full-thickness mucoperiosteal flap elevation; granulation tissue removal using Teflon
curettes and irrigation with sterile saline (Gracey; Hu-Friedy) [48].For participants
allocated to NMP gel, apply ImplanTreat® gel on the implant/abutment surface and on the
rotary brush that will move at a speed of 2,500 rpm for ~20 seconds. For the control group,
no gel will be applied. The surface will be brushed thoroughly until all visual contaminants
are removed, followed by water irrigation to remove contaminants and any remaining gel.
Postoperative follow-up will take place after 2 weeks. During the first 2 weeks after
surgery, no oral home care should be done by the participants. Thereafter, participants will
be told to resume routine oral hygiene. Data will be collected in a blinded fashion by a
trained and calibrated dental professional (dentist or dental hygienist) using study
questionnaires, a clinical form, and standardized radiographs (using an occlusion jig
material). Follow-up data collection will be performed at 4 weeks and at 6 months by the same
examiner at each research center. Since this is a multicenter clinical trial, and in order to
avoid bias in data collection and measurements, the PI (or Co-PI) will visit each center to
train and calibrate collaborators in the other centers. Standardization will concern all
study procedures, from screening potential participants to data collection and measurements.
In addition, regular meetings (in person or video calls) between the PI (or Co-PI) and the
principal collaborator in each center will be planned to ensure the trial follow-up.
Clinical and radiographic assessment: To assess the potential efficacy of NMP gel, outcomes
include clinical and radiological measurements. Periodontal examination at 6 sites around
each included implant (mesiobuccal, buccal, distobuccal, mesiolingual/ palatal, lingual and
distolingual/palatal) will be performed to record the clinical periodontal indices and for
every clinical index, a mean value will be calculated based on the average of the obtained
values in the 6 examined sites around the implant. The primary outcome will be probing depth
(PD), which will be measured in millimeters around the implant, using a UNC15 periodontal
probe. Other secondary outcomes will be:
Modified Gingival Index (MGI) in which the gingivae are given a score on a five-point scale
from 0 (absence of inflammation) to 4 (severe inflammation) [49].
Modified plaque index (mPI) will be recorded by running the periodontal probe across the
marginal surface of the implant and recording either the absence or the presence of plaque as
follows: A score of 0 represents no plaque, 1 represents separate flecks of plaque at the
cervical margin; 2 represents plaque can be seen by naked eye, 3 represents abundance of soft
matter.
Bleeding on probing (BoP) will be recorded using a 3-graded index 10s after probing as
follows: A score of 0 represents no bleeding, 1 represents isolated minimal bleeding spots, 2
represents blood forming a confluent red line on the margin and 3 represents heavy or profuse
bleeding.
Suppuration (Sup) will be evaluated by assessing the presence or absence of suppuration up to
15 seconds after probing.
Radiographic crestal bone level (CBL) will be measured on the intraoral periapical
radiographs at baseline and at 6 months follow-up to assess the effect of ImplanTreat® on
peri-implant bone remodeling. CBL will be measured by the distance from the implant/abutment
interface to the first bone-to-implant contact on both the mesial and distal implant side.
CBL will be recorded by calculating the average distances between the mesial and distal
sides[48]. In order to avoid any bias, one investigator, blinded to the treatment group, will
use the same X-ray device, with the same settings, for pre- and post-intervention
radiographs, following a standardized procedure.
Descriptive analysis will be performed on the sociodemographic and explanatory variables. The
normality of the distribution of the primary outcomes data will be initially tested. T-test
and a repeated measure analysis of variance (ANOVA) will be used to compare the mean
differences in the continuous variables from baseline to 4 weeks and 6 months
post-intervention, between the group who received the gel cleaning with ImplanTreat® and the
controls. In the case of non-normal data distributions, the Mann-Whitney and Friedman tests
will be used instead of the t-test and ANOVA, respectively. P values will be considered as
statistically significant if less than 0.05.
The primary outcome for the group I is the absence of bleeding on probing (BoP). Considering
a clinically relevant difference of 20% in terms of frequency in BoP-positive sites between
the two study groups at the 4-week follow-up, a sample size of 100 patients per treatment
group has 80% power to detect a significant difference (α = 0.05) based on variability data
from Lerario et al. (2016)[52]. To compensate for possible dropouts, the sample size will be
increased by 10%, requiring 220 patients; including 110 test participants and 110 controls.
The sample size has been calculated for Group II using PD as the primary outcome (Power and
Sample Size Calculations Software, Version 3.0, Vanderbilt University, Nashville, TN, USA).
In order to detect a 40% difference in terms of PD reduction between groups after 6 months
with a p-value of 0.05 and 85% statistical power a sample of 154 participants will be
required (77 participants per group) (Schwarz F et al 2013). The researchers anticipate an
attrition rate of 10%. Consequently, 170 participants including 85 test participants and 85
controls.
