Clinical trial NCT04210596: Connective Tissue Graft Versus Collagen Matrix
Official title: A Multicenter Randomized Controlled Study Comparing Connective Tissue Graft with Collagen Matrix to Re-establish Convexity At the Buccal Aspect of Single Dental Implants
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Buccal Soft Tissue Profile (BSP)
Keywords: connective tissue graft
collagen matrix
dental implant, single tooth
volumetric analysis
Lead sponsor: University Ghent
Sponsor class: OTHER
Collaborators: name: Osteology Foundation
First posted: 2019-12-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter randomized controlled study with 2 treatment arms (control: connective tissue graft; test: collagen matrix) and 6 centers
Primary purpose: TREATMENT

Brief summary: Patients in need of a single implant in the premaxilla and presenting with a horizontal buccal soft tissue defect at the single tooth gap will be invited to participate in a multicenter RCT. Prior to surgery, a small-field low-dose CBCT is taken since a buccopalatal bone dimension of at least 6 mm at the central and crestal aspect of the single tooth gap is required to ensure complete embedding of an implant by bone. Sixty patients will be randomly allocated to the test group or control group in 6 centers. Each center receives 10 sealed envelopes (5 are internally labelled with 'test group' and 5 with 'control group').

For each patient a digital planning is performed in implant planning software and a tooth-supported surgical guide is fabricated. In the control group, a single implant is placed following flap elevation and surgical guide installation. Then, a CTG from the palate is positioned under the buccal mucosa to thicken the tissues. A provisional restoration is placed at the day of surgery, which is replaced by a permanent one 3m later. Patients in the test group are treated in the same way, yet a CM (Fibro-Gide®) is used instead of a CTG.

Changes in the buccal soft tissue profile are registered over time by superimposing intra-oral scans in SMOP® software.

Secondary outcomes included clinical, aesthetic and patient-reported outcomes.

Detailed description: Patients will be included in a multicenter RCT following screening and after having received written consent.

A sample size calculation using the Satterthwaite t-test was performed in SAS Power and Sample Size based on a comparison of mean change in BSP (primary outcome variable) from baseline to 1 year between the control group and test group. The calculation was based on finding a mean difference of at least 0.5 mm between these groups with a standard deviation of 0.5 mm for CTG and 0.7 mm for CM (as adopted from Zeltner et al. 2017). With alpha set at 0.05 and a power of 0.80, the sample size calculation indicated 25 patients to be included per group. To compensate for drop-outs, 30 patients would be treated with CTG and 30 would be treated with CM.

Clinicians and centers, randomization, allocation concealment and blinding Six experienced clinicians will treat 10 patients each. All clinicians are staff members of the Department of Periodontology and Oral Implantology at UGent - UZ Gent, who also work part-time in different private practices. The digital workflow, the implant placement protocol, the application of CTG and CM and the restorative protocol will be thoroughly discussed among the 6 clinicians in a training session before the start of the trial.

During the training session each clinician will receive 5 sealed envelopes internally coded as 'CTG' and another 5 as 'CM'. Just prior to surgery, a sealed envelope will be randomly selected and opened to reveal the treatment to be conducted. The measuring investigator will not be involved in the treatment of any of the patients and will be blinded to allow unbiased registrations.

Pre-operative digital planning A full digital workflow will be adopted for every patient. This implies the fabrication of a stereolythographic surgical guide on the basis of a 3D digital implant planning in designated software (NobelClinician, Nobel Biocare, Zürich, Switserland). A low-dose small-field Cone-Beam CT and intra-oral scan are required for this purpose. The same software will also be used to design a provisional acrylic crown, which will be adapted chairside immediately following surgery (Tempshell, Nobel Biocare, Zürich, Switserland).

Surgery Control group: soft tissue augmentation with CTG Patients start to take systemic antibiotics (Amoxicilline 1g) and anti-inflammatory medication (ibuprofen 600 mg) 1h pre-operatively. Following local anesthesia (Septanest special, Septodont, Saint Maur des Fossés, France) and oral disinfection (Corsodyl mouth rinse, GSK, Wavre, Belgium), a conventional mucoperiosteal flap will be raised. Thereupon, the surgical guide is positioned and a dental implant (NobelReplace CC PMC, Nobel Biocare, Zürich, Switserland) is installed. A CTG is harvested from the palatal mucosa in the premolar area by means of the single-incision technique as described by De Bruyckere et al. (2015) (fig. 1). The CTG is pulled into the envelope and fixed with two sutures (Seralon 6/0, Serag Weissner, Naila, Germany). Tension-free primary wound closure with the same suture material is pursued around a provisional acrylic crown. Post-op instructions include the intake of systemic antibiotics during 4 days (Amoxicilline 1g, two times a day), anti-inflammatory medication as deemed necessary by the patient and oral disinfection twice a day during 1 week. Then, sutures are removed. After 3 months, the provisional crown will be replaced by a permanent crown by the general dentist.

Test group: soft tissue augmentation with CM In the test group, no CTG is harvested as it will be replaced by CM (Fibro-Gide, Geistlich Biomaterials, Wolhusen, Switserland). Apart from that, all pre-op, surgical and post-op procedures are identical in the control group and test group.

Prior to surgery (baseline = t0), at 3 months (t1), 1 year (t2) and 5 years (t3) an intra-oral optical scan of the implant site and neighboring teeth will be taken (Trios, 3shape, Copenhagen, Denmark). The region of interest (ROI) will be defined on STL files with a trapezoid shape encompassing the following borders: 1 mm apical to the midbuccal soft tissue level (coronal), the mucogingival junction (apical) and 1 mm distance from the neighbouring tooth at both sides (mesial, distal). This ROI may vary between patients due to anatomical variation but will be kept constant in each patient and site over time. The STL images of baseline and follow-up will be superimposed and matched using the best-fit algorithm at the adjacent tooth surfaces. The linear changes in BSP will be measured in the middle of the ROI, calculated by the software and expressed in mm corresponding to the mean distance between the surfaces representing the evaluated time points (t0, t1, t2, t3).

All patients are scheduled for suture removal and oral hygiene instructions after 1 week with registration of:

Postoperative bleeding, Pain and amount of anti-inflammatory medication taken, Oedema and Hematoma.

After 3 months, 1 year and 2 years, all patients are scheduled for a clinical and radiographic follow-up visit, including registration of mesial and distal marginal bone level. Intra-oral radiographs will be taken using the long-cone parallel technique. Bone levels will be assessed and defined as the distance from the implant-abutment interface to the first bone-to-implant contact to the nearest 0.1 mm. Clinical parameters ,such as probing pockets depths (mm), plaque (presence or absence) and bleeding on probing (presence or absence) are registered as well as vertical soft tissue levels at the midbuccal aspect to the nearest 0.5 mm. White and Pink esthetics are assessed according to Furhauser.

Eligibility criteria: Inclusion Criteria:

* at least 18 years old
* good oral hygiene defined as full-mouth plaque score ≤ 25%
* presence of a single tooth gap in the anterior maxilla (15-25) with both neighboring teeth present
* failing tooth at least 3 months earlier removed
* class I defect at the single tooth gap as clinically assessed (buccopalatal loss of tissue with a normal apicocoronal ridge height)
* buccopalatal bone dimension of at least 6 mm at the central and crestal aspect of the single tooth gap to ensure complete embedding of an implant by bone.

Exclusion Criteria:

* systemic diseases
* smoking
* (history of) periodontal disease;
* untreated caries lesions
* need for horizontal bone augmentation at the time of implant placement

Primary outcomes:
measure: Changes in buccal soft tissue profile (BSP)
timeFrame: Pre-op, 3 months, 1 year, 2 years
Secondary outcomes:
measure: Changes in Probing pocket depth
timeFrame: 3 months, 1 year, 2 years
measure: Changes in Bleeding on probing
timeFrame: 3 months, 1 year, 2 years
measure: Changes in Plaque Index
timeFrame: 3 months, 1 year, 2 years
measure: Changes in radiographic outcomes
timeFrame: 3 months, 1 year, 2 years
measure: Patient-reported outcome measures
timeFrame: 1 week
measure: Patient-reported outcome measures
timeFrame: 1week
measure: Patient-reported outcome measures
timeFrame: 1 week
measure: Patient-reported outcome measures
timeFrame: 1 week
measure: Patient-reported outcome measures
timeFrame: 1 week
measure: Patient-reported outcome measures
timeFrame: 3 months
measure: Patient-reported outcome measures
timeFrame: 1 year
measure: Patient-reported outcome measures
timeFrame: 2 years
measure: Patient-reported outcome measures
timeFrame: 1 week
measure: Patient-reported outcome measures
timeFrame: 3 months
measure: Patient-reported outcome measures
timeFrame: 1 year
measure: Patient-reported outcome measures
timeFrame: 2 years
measure: Aesthetic outcome as assessed by care providers
timeFrame: 1 year
measure: Aesthetic outcome as assessed by care providers
timeFrame: 2 year
measure: Aesthetic outcome as assessed by care providers
timeFrame: 1 year
measure: Aesthetic outcome as assessed by care providers
timeFrame: 2 years
measure: Surgery time
timeFrame: At Surgery
measure: Primary stability
timeFrame: At Surgery
measure: Incremental cost-effectiveness ratio
timeFrame: baseline - 2 years
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University
state: Oost-Vlaanderen
Study officials:
References:
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