NCT06820489 | NOT YET RECRUITING | Bone Resorption

Detailed Description:

Aim The primary study objective is to compare the gold standard augmentation technique (conventional CTG = C-CTG) to two alternatives, being scarf CTG (S-CTG) and dual zone concept (DZ) in a superiority RCT, in terms of the proportion of cases with successful regeneration at 1 mm below the implant shoulder using the following PICO elements: P Patients undergoing single IIP in the anterior maxilla (tooth 15-25) I S-CTG or DZ C C-CTG O Proportion of cases with successful regeneration at 1 mm below the implant shoulder Secondary study outcomes relate to the same comparison, yet focus on clinical and patient-reported outcomes, soft tissue changes and aesthetic outcomes. Methodology Inclusion and exclusion criteria Inclusion criteria are as follows: at least 20 years old; good oral hygiene defined as full-mouth plaque score ≤ 25% (O'Leary et al. 1972); presence of an incisor, cuspid or premolar in the maxilla that needs to be extracted for any reason with at least one neighboring tooth present; at least 3 mm bone available at the apical or palatal aspect of the alveolus as assessed on CBCT to ensure primary implant stability; intact buccal bone wall (type I) or limited buccal bone dehiscence (type IIa or IIb) at the time of extraction; written informed consent. Exclusion criteria are as follows: pregnancy; systemic diseases; smoking; suppuration; \> 1 mm gingival asymmetry between the failing and contralateral tooth; untreated periodontal disease; untreated caries lesions. Sample size calculation A recent RCT indicated successful regeneration at 1 mm below the implant shoulder in 82% of the cases treated with C-CTG (Cosyn et al., 2024). Since none of the alternative options augment hard and soft tissues at this level, it is expected that S-CTG as well as DZ achieve 50% less success. Using a two-sided Chi-square test, a sample size of 45 patients (15 in each group) would be needed to achieve such absolute risk difference between the control group and either test group (C-CTG versus S-CTG; C-CTG versus DZ) with at least 80% power at the 5% significance level. The sample size would be increased to 18 patients per group to compensate for possible drop-outs. The sample size calculation was performed using SPSS Statistics 28 (IBM, New York, USA). Randomization, allocation concealment and blinding Patients will be randomly assigned to either C-CTG, S-CTG or DZ. Fifty-four sealed envelopes are prepared for that purpose, of which 18 are internally labeled as C-CTG, 18 as S-CTG and 18 as DZ. Following IIP, a sealed envelope will be opened to reveal the treatment concept. Group allocation will be revealed following implant installation and will remain concealed for the evaluating examiner and statistician to allow for unbiased registrations and analyses, respectively. Surgical procedures All surgeries will be performed by two implant surgeons (JC, TDB) at Ghent University Hospital. Patients will be prescribed amoxicillin for 4 days (2 times 1 g per day started 1h before surgery), analgesics (ibuprofen 600 mg) as deemed necessary and oral disinfection (chlorhexidine rinse 2 times per day during one week). Irrespective of the group, a cutting implant (BLX, Straumann, Basel, Switzerland) is installed in an optimal 3D position using a surgical guide. Socket grafting is performed with DBBM (Bio-Oss® 0.25 - 1 mm, Geistlich Pharma AG, Wolhusen, Switzerland) to limit buccal bone resorption and to optimize soft tissue stability (Seyssens et al., 2022). For patients allocated to C-CTG, a pouch is made in the buccal mucosa extending 3 mm below the buccal bone crest using microsurgical instruments. Thereupon, a free gingival graft with a height of 6 mm and thickness between 1 mm and 2 mm is harvested from the palatal mucosa and de-epithelialized. The length depends on the mesiodistal size of the tooth gap, which varies between 6 mm and 9 mm. Then, the CTG is brought into the pouch and fixed with two single sutures (Seralon 6/0, Serag Wiessner, Naila, Germany) onto the buccal mucosa. Finally, a healing abutment is installed, which is replaced by a provisional implant crown 2 days later. Sutures are removed 1 week after the surgery. For patients allocated to S-CTG, no pouch is made at the recipient site and a CTG with a height of only 3 mm is harvested from the palate in the way as described above for C-CTG. The small CTG is fixed at the transmucosal aspect (Seralon 6/0, Serag Wiessner, Naila, Germany) onto the buccal mucosa. Again, a healing abutment is installed, which is replaced by a provisional implant crown 2 days later. Sutures are removed 1 week after the surgery. For patients allocated to DZ, DBBM is applied and condensed up to the level of the buccal soft tissue margin. A healing abutment is installed, which is replaced by a provisional implant crown 2 days later. Usually, sutures are not needed in this group, unless minimal papilla opening was required to extract the tooth. In that case, sutures will be removed after 1 week. CBCT analysis A CBCT is taken pre-operatively and at one-year follow-up. CBCT images are obtained using a ProMax 3D Max device (Planmeca, Helsinki, Finland) with the same standardized settings (90 kV, 6.3 mA, 9 s, voxel size 200 μm) with a same field of view (50 x 80 mm2) for each patient. Lip retractors are used to clearly visualize the external soft tissue profile, and patients are instructed to fold the tongue backwards for the same reason. Using specialized software (Invivo6, Osteoid Inc., Santa Clara, CA, USA) CBCT images from the different timepoints are superimposed (figure 1). A reference line is constructed through the long axis of the implant on the 1-year CBCT. A second reference line perpendicular to the long axis is drawn at the level of the implant-abutment interface. Another line is constructed parallel to the second reference line at 1 mm apical to the implant-abutment interface (so-called level -1 mm). Horizontal buccal bone loss Horizontal buccal bone level is measured as the distance from the long axis of the implant to the buccal bone surface at level -1 mm. Then, the software switches to the superimposed pre-operative CBCT image to do the same measurement while keeping all reference lines. Horizontal buccal bone loss at level -1 mm is calculated by subtracting the pre-operative horizontal buccal bone level from the 1-year horizontal buccal bone level, both at level -1 mm. Hence, negative values represent bone loss. The same methodology is applied to determine horizontal buccal bone loss at level -3 and -5 mm. Vertical buccal bone loss Vertical buccal bone level is measured as the vertical distance from the buccal bone peak to the reference line at the level of the implant-abutment interface to the nearest 0.1 mm (figure 1). This is registered on the pre-operative CBCT and on the 1-year CBCT. Vertical buccal bone loss is calculated by subtracting the pre-operative vertical bone level from the 1-year vertical bone level. Hence, negative values represent bone loss. Increase in buccal soft tissue thickness Buccal soft tissue thickness is measured as the distance from the buccal bone surface to the buccal soft tissue profile at level -1 mm to the nearest 0.1 mm. This is registered on the pre-operative CBCT and on the 1-year CBCT. Increase in buccal soft tissue thickness is calculated by subtracting its pre-operative value from the 1-year value. Hence, positive values represent tissue gain. Succesful regeneration Successful regeneration (primary outcome) is achieved when the combination of socket grafting and transmucosal augmentation (C-CTG or S-CTG or DZ) would be able to counteract any buccal soft tissue loss at level -1 mm. It is assessed on the basis of superimposed CBCTs taken pre-operatively and at one-year follow-up. Patient-reported outcomes One week after surgery, patients will be asked how many analgesics have been taken. In addition, they will be asked to rate postoperative pain on a numeric rating scale (0-10). Clinical outcome Plaque, bleeding on probing and probing depth. At 1-year and 5-year follow-up the treating surgeon evaluates plaque, bleeding on probing and probing depth at four sites around the implant (mesial, buccal, distal, palatal). Each area receives a score of 0 or 1, representing the absence or presence of plaque or bleeding on probing. Probing depth is registered with a manual probe (University North Carolina Probe PCPUNC 156, Hu-Friedy, Frankfurt, Germany) and measurements are rounded up to the nearest 0.5 mm. A mean value is calculated per implant. Marginal bone loss. Peri-apical radiographs are taken with the long-cone paralleling technique at implant placement, 1-year and 5-year follow-up. Measurements are performed by a blinded examiner in designated software (DBSWIN Imaging Software, Dürr Dental SE, Bietigheim-Bissingen, Germany). Radiographs are calibrated on the basis of implant length. The distance from the implant-abutment interface to the initial bone-to-implant contact - called bone level - is assessed at the mesial and distal aspects of each implant. Marginal bone loss is calculated by subtracting the 1-year bone level and 5-year bone level from the pre-operative bone level. Hence, negative values represent bone loss. Per implant a mean value is calculated. Soft tissue changes Change in buccal soft tissue profile. An intra-oral scan (Trios, 3shape, Copenhagen, Denmark) is taken prior to surgery and at 1-year and 5-year follow-up. The obtained digital surface models in STL (Surface Tessellation Language) format are imported into the designated software (SMOP, Swissmeda AG, Zurich, Switzerland) to analyze profilometric changes. A study-relevant area of interest (AOI) at the buccal aspect is selected for each site. The AOI extends from the soft tissue margin to 3 mm more apical. In mesio-distal dimension, the AOI reaches from the mesial to the distal line angle. The AOI may vary between sites because of individual anatomic differences but must be kept constant in each site across time points. Digital surface models are superimposed using the best-fit algorithm at unchanged adjacent tooth surfaces. A mean volumetric change (mm3) within the AOI for each site from prior to surgery to 1-year and 5-year follow-up is calculated by the software and divided by the AOI, resulting in the mean change in buccal soft tissue profile. Change in buccal soft tissue profile is assessed by a blinded examiner. Change in midfacial soft tissue level Change in midfacial soft tissue level from surgery to 1-year and 5-year follow-up is calculated on digital surface models from in the same software (SMOP, Swissmeda AG, Zurich, Switzerland). First, a reference line is drawn connecting the middle of the incisal edge on both adjacent teeth at both timepoints. Then, the distance from this line to the buccal mucosal margin (so-called midfacial soft tissue level) is determined at the centre of each implant to the nearest 0.01 mm. Change in midfacial soft tissue level Calculated by subtracting midfacial soft tissue level from the preoperative situation from the one at 1-year and 5-year follow-up. Negative values indicate recession; positive values indicate vertical regrowth. Change in midfacial soft tissue level is assessed by a blinded examiner. Change in mesial and distal papilla level Calculated at the mesial and distal aspect from surgery to 1-year and 5-year follow-up. The methodology is the same as described for the change in midfacial soft tissue level. Aesthetic outcome Pink Esthetic Score (PES) (Fürhauser et al., 2005) is registered by a trained and blinded examiner using frontal and occlusal clinical pictures taken at 1 year and 5-year follow-up. The PES results in a score from 0 (worst esthetic outcome) to 14 (perfect esthetic outcome). Statistical analysis SPSS Statistics (SPSS inc., Chicago, IL, USA) is used for data analysis. Inter-rater reliability of hard and soft tissue registrations is assessed on the basis of duplicate measurements of 10 cases and calculation of the intra-class correlation coefficient (ICC). Duplicate measurements are performed by a blinded experienced examiner. For buccal hard and soft tissue changes a linear mixed model with random intercept for patient is fitted including treatment group, time and their two-way interaction as fixed effects. For horizontal buccal bone loss at the different levels, pre-operative buccal bone thickness (assessed to the nearest 0.1 mm on the pre-operative CBCT) and the horizontal dimension of the buccal bone gap (intra-operatively assessed with a periodontal probe to the nearest 0.5 mm immediately following IIP and prior to socket grafting) are included as covariates to increase precision of the estimates. For vertical buccal bone loss, pre-operative vertical buccal bone level is included as covariate and for increase in buccal soft tissue thickness, pre-operative buccal soft tissue thickness is included as covariate. Estimated marginal means with 95 % confidence intervals (CIs) are computed per treatment group (FDA, 2023). The number of patients with successful regeneration are compared between the control group and the test groups (C-CTG versus S-CTG and C-CTG versus DZ) using the Fisher's exact test. The number of sites with plaque or bleeding on probing is compared between the control group and the test groups using negative binomial regression. Medians and interquartile ranges are calculated for probing depth, marginal bone loss, change in buccal soft tissue profile, change in mesial and distal papilla level, and PES. The control group is compared to the test groups using the Mann-Whitney U-test at 1-year and 5-year follow-up. Independent samples Hodges-Lehmann median differences and 95% CIs are calculated. All hypothesis testing is performed at the two-sided 5% significance level.