Clinical trial NCT04741607: Immediate Versus Late Placement
Official title: Alveolar Ridge Preservation With Immediate or Late Implant Placement: a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Esthetics
Keywords: connective tissue graft
dental implant, single tooth
immediate
ridge preservation
Lead sponsor: University Ghent
Sponsor class: OTHER
First posted: 2021-02-05
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: delayed implant placement; test: immediate implant placement) and 6 centers
Primary purpose: TREATMENT

Brief summary: Patients in need of a single implant in the premaxilla will be invited to participate in this multicenter randomized controlled trial (RCT). Prior to surgery, a small-field low-dose cone beam computed tomography (CBCT) is taken to verify the integrity of the facial bone wall and an adequate amount of apical and palatal bone dimensions. 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 'delayed implant placement' and 5 with 'immediate implant placement').

For each patient a digital planning is performed in implant planning software and a tooth-supported surgical guide is fabricated prior to tooth extraction.

In the control group, alveolar ridge preservation is performed following tooth extraction. After a healing period of 4 months, a single implant is installed.

In the test group, a single implant is installed immediately after tooth extraction and ridge preservation is performed by filling the gap between the facial bone wall and the implant surface.

A provisional crown is placed at the day of implant surgery, which is replaced by a permanent one 3m later.

Six months after tooth extraction and subsequent ridge preservation, the need for soft tissue grafting is assessed on the base of predetermined criteria (primary outcome measure). Soft tissue augmentation is performed by inserting a palatal connective tissue graft (CTG) into the buccal mucosa at the implant site.

Secondary outcome measures include 3D hard and soft tissue changes as well as clinical, aesthetic, patient-reported and clinician-reported outcomes.

Detailed description: Patient selection Patients in need of a single implant in the premaxilla (15-25) will be included in this multicenter RCT following screening and after having received written consent.

Sample size calculation A sample size calculation using the Pearson Chi-square test was performed in SAS Power and Sample Size based on a comparison of the proportion on the need for soft tissue augmentation at 5 months following alveolar ridge preservation (ARP) between the control group (ARP + delayed implant placement 'DIP') and test group (ARP + immediate implant placement 'IIP'). The calculation was based on finding a 30% difference between these groups. With alpha set at 0.05 and a power of 0.80, the sample size calculation indicated 28 patients to be included per group. To compensate for drop-outs, 30 patients would be treated with ARP+DIP and 30 would be treated with ARP+IIP.

Clinicians and centers, randomization, allocation concealment and blinding Six experienced clinicians will treat at least 10 patients each. Five 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 final clinician is a professor at the Saint-Luc University Hospital (UCL). The digital workflow, the implant placement protocol, the application of a connective tissue graft (CTG) at 6 months following ARP 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 'Delayed implant placement' and another 5 as 'immediate implant placement'. 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 for fabrication of surgical guide A digital workflow will be adopted for every patient for fabrication of a surgical guide prior to tooth extraction. This requires 3D digital implant planning in designated software on the basis of a pre-op low-dose small-field Cone-Beam CT and intra-oral scan. Note that surgical guides for patients in the ARP+DIP group will also be fabricated following patient selection, even though they are only to be used 4 months later.

Control group: ARP+DIP 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), the failing tooth is extracted without raising a flap. Following socket debridement and rinsing, collagen-enriched DBBM (Bio-Oss Collagen 250 mg, Geistlich Pharma AG, Wolhusen, Switserland) is applied up to the level of the palatal bone crest and slightly condensed. The occlusal aspect is closed with a collagen matrix (Mucograft Seal, Geistlich Pharma AG, Wolhusen, Switserland), which is fixed with single sutures (Seralon 6/0, Serag Weissner, Naila, Germany) to the soft tissues. 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. A removable partial denture as used as provisional tooth replacement when considered needed.

At 4 months, a mucoperiosteal flap is raised, the surgical guide is applied, and the implant is installed according to manufacturer's prescriptions. Then, an implant impression is taken for fabrication of a provisional crown. Prior to wound closure with vertical mattrass sutures (Seralon 6/0, Serag Weissner, Naila, Germany), an appropriate healing abutment is installed. This healing abutment is replaced by the provisional crown two days later.

At 6 months, the need for soft tissue augmentation is assessed by the 5 clinicians who have not been clinically involved. The treating clinician is excluded since he/she cannot be blinded for the treatment group. The need for soft tissue augmentation is assessed on the basis of screenshots from the pre-op CBCT with lip retractors enabling to evaluate buccal bone and soft tissue thickness. Pre-op clinical pictures, clinical pictures at 6 months with the provisional crown in situ and the STL file at 6 months are also offered to the panel in order to assess the loss of buccal convexity.

Soft tissue augmentation is required necessary when at least one of the following criteria are met: thin gingival biotype as defined as \< 1mm midfacial soft tissue thickness as assessed on pre-op CBCT with lip retractors, thin buccal bone wall as defined as \< 0.5mm as assessed on pre-op CBCT, loss of ideal buccal convexity at 6 months following ARP as assessed on the basis of clinical pictures and STL. Each clinician makes a decision on the need for soft tissue augmentation for 50 out of 60 cases independent from the other clinicians. Soft tissue augmentation is offered to the patient when the majority of the panel is in favor of it.

Soft tissue augmentation is performed using a CTG harvested from the lateral palate using the single incision technique. At the recipient site, a pouch is made in the buccal mucosa and an appropriately sized CTG is pulled in. The CTG is secured into the buccal mucosa with multiple single sutures (Seralon 6/0, Serag Weissner, Naila, Germany) and the provisional crown is re-installed. Sutures are removed after 1 week. The provisional crown is replaced by a permanent crown 3 months later.

Test group: ARP+IIP 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), the failing tooth is extracted without raising a flap. Following socket debridement and rinsing, the surgical guide is applied, and the implant is installed according to manufacturer's prescriptions. Then, an implant impression is taken for fabrication of a provisional crown. Finally, the gap is filled with collagen-enriched DBBM (Bio-Oss Collagen 250 mg, Geistlich Pharma AG, Wolhusen, Switserland), which is applied up to the level of the free mucosal margin, and an appropriate healing abutment is installed. This healing abutment is replaced by the provisional crown two days later.

At 6 months, the need for soft tissue augmentation is assessed by the 5 clinicians who have not been clinically involved. The treating clinician is excluded since he/she cannot be blinded for the treatment group. The need for soft tissue augmentation is assessed on the basis of screenshots from the pre-op CBCT with lip retractors enabling to evaluate buccal bone and soft tissue thickness. Pre-op clinical pictures, clinical pictures at 6 months with the provisional crown in situ and the STL file at 6 months are also offered to the panel in order to assess the loss of buccal convexity. Each clinician makes a decision on the need for soft tissue augmentation for 50 out of 60 cases independent from the other clinicians. Soft tissue augmentation is offered to the patient when the majority of the panel is in favor of it.

Soft tissue augmentation is performed using a CTG harvested from the lateral palate using the single incision technique. At the recipient site, a pouch is made in the buccal mucosa and an appropriately sized CTG is pulled in. The CTG is secured into the buccal mucosa with multiple single sutures (Seralon 6/0, Serag Weissner, Naila, Germany) and the provisional crown is re-installed. Sutures are removed after 1 week. The provisional crown is replaced by a permanent crown 3 months later.

Eligibility criteria: Inclusion Criteria:

* at least 18 years old
* good oral hygiene defined as full-mouth plaque score ≤ 25% (O'Leary et al. 1972)
* presence of a single-rooted tooth in the anterior maxilla (15-25) 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 to ensure primary implant stability
* intact or nearly intact buccal bone wall at the time of extraction (max 3 mm bone missing = max 6 mm distance from free gingival margin to buccal bone crest)

Exclusion Criteria:

* systemic diseases
* smoking
* untreated periodontal disease
* untreated caries lesions

Primary outcomes:
measure: Need for soft tissue augmentation (true or false) as judged by a panel of clinicians
timeFrame: 6 months
Secondary outcomes:
measure: Clinician-reported outcome measures
timeFrame: per-op
measure: Changes in buccal soft tissue profile
timeFrame: pre-op, 6 months, 1 year, 3 years, 5 years
measure: Vertical change in midfacial soft tissue level
timeFrame: pre-op, 6 months, 1 year, 3 years, 5 years
measure: Change in width of the alveolar process
timeFrame: pre-op, 1 year, 5 year
measure: Change in height of the alveolar process
timeFrame: pre-op, 1 year, 5 year
measure: Change in buccal bone thickness
timeFrame: pre-op, 1 year, 5 year
measure: Implant survival
timeFrame: 6 months, 9 months, 1 year, 3 years, 5 years
measure: Complication
timeFrame: Up to 5 years
measure: Changes in radiographic outcomes
timeFrame: implant placement, 1 year, 3 years, 5 years
measure: Aesthetic outcome as assessed by care providers
timeFrame: pre-op, 1 year, 3 years, 5 years
measure: Aesthetic outcome as assessed by patients
timeFrame: pre-op, 1 year, 3 years, 5 years
measure: Keratinized mucosa width
timeFrame: pre-op, 1 year, 3 years, 5 years
measure: Probing pocket depth
timeFrame: pre-op, 1 year, 3 years, 5 years
measure: Bleeding on probing
timeFrame: pre-op, 1 year, 3 years, 5 years
measure: Plaque
timeFrame: pre-op, 1 year, 3 years, 5 years
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University
state: Oost-Vlaanderen
city: Liège
country: Belgium
facility: UCL St Luc
Study officials:
References:
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