Clinical trial NCT05211115: Autogenous vs. Xenogeneic Peri-implant Soft Tissue Grafts Placed in Full vs. Split Thickness Flaps
Official title: Randomised Clinical Trial Comparing Autogenous vs. Xenogeneic Peri-implant Soft Tissue Grafts Placed in Full vs. Split Thickness Flaps: a Clinical, Histological and Vascular Analysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Thin Gingiva
Keywords: Soft tissue management
Dental implant
Collagen matrix
Connective tissue graft
Split thickness flap
Full thickness flap
Lead sponsor: Universidad Complutense de Madrid
Sponsor class: OTHER
Collaborators: name: Osteology Foundation
First posted: 2022-01-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized, outcome assessor and data analyst blinded, single center trial with four parallel arms and a 1:1:1:1 allocation ratio, with the aim of comparing which combination of bilaminar technique (split vs. full thickness flap) and graft type (autogenous or xenogeneic) provides better clinical, aesthetic, morphological, vascular and patients related outcomes, when augmenting the buccal peri-implant mucosa at the reopening of submerged implant fixtures

Detailed description: This randomized four parallel arms controlled clinical trial with blinded outcome assessment and data analysis aims to establish which combination of bilaminar technique (split vs. full thickness flap) and graft type (autogenous subepithelial connective tissue graft vs. volume stable collagen matrix) provides better clinical, aesthetic, morphological, vascular and patients related outcomes, when augmenting the buccal peri-implant mucosa at the reopening of submerged implant fixtures. The primary outcome is the gain in soft tissue thickness (standardised measurement at baseline, after surgery, at 1m and 6m). Secondary outcomes include changes in tissue volume (intraoral scans at baseline, post-op, 14d, 1m, 6m), RAL and KTW (clinical measurements at baseline, 1m, 6m), tissue color integration (∆E at 1m and 6m), and PROMS (7d, 14d, 30d). Exploratory outcomes include tissue morphology (histology at 1m,2m,4m,6m), microcirculation (Doppler flowmetry at pre-op, 7d, 14d, 1m) and revascularization (IHC at 1m,2m,4m,6m). A figure of 10 subjects per group was obtained for a 0,3mm difference in tissue thickness increase (SD 0,23mm), using 80% power, alpha 0.05, and a 10% drop-out rate. Patients will be randomly allocated to four groups: test (STF+VCM), control 1 (FTF+VCM), control 2 (SFT+CTG), control 3 (FTF+CTG). Patients will be the unit of analysis and ANOVA (normality) or Kruskall-Wallis (no normality) tests will be performed setting the significance level at p \< 0.05.

Eligibility criteria: Inclusion Criteria:

Any male or female adult (≥ 18 year old) patient from the University Complutense of Madrid, being able to sign an informed consent form, presenting a submerged dental implant scheduled to undergo a second stage surgery, which is bounded mesially or distally by a remaining natural tooth, and exhibits a lack of buccal soft tissue volume, will be potentially eligible for this trial.

The case definition for a lack of buccal soft tissue volume will be the presence of a thin buccal mucosa (\< 2mm) or a minor volumetric contraction of the alveolar process (flat or concave buccal mucosal profile at the edentulous area).

Exclusion Criteria:

Patients fitting to all the above inclusion criteria will be not included in the study if unable to attend to the study-related procedures (including the follow-up visits) or if one or more of the following systemic or local exclusion criteria will be found during enrolment or through the study:

Systemic primary exclusion criteria:

* Compromised general health status contraindicating the study procedures (≥ASA IV);
* Drug abuse, alcohol abuse, or smoking \> 10 cigarettes a day;
* Chronic use of corticosteroids, NSAIDs, or immune-modulators (any type, any dose);
* Assumption of bisphosphonates (any type, any dose, past or present);
* Pregnant or nursing women;
* Hypersensitivity to paracetamol;

Local primary exclusion criteria

* History of previous mucogingival surgeries in the area of interest;
* Lack of adequate vestibule depth to perform a bilaminar procedure;
* Lack of osseointegration at the time of implant reopening;
* Need for additional bone grafting at the time of implant reopening;
* Intraoperative evidence of a flap thickness \< 0,5mm or \> 2mm.

Secondary exclusion criteria:

- Non compliant patients: poor oral hygiene at 2 consecutive visits.

Primary outcomes:
measure: Buccal soft tissue thickness
timeFrame: before surgery, after surgery, 1 month after surgery, 6 months after surgery
Secondary outcomes:
measure: Volume changes
timeFrame: before surgery, after surgery, 14 days after surgery, 1 month after surgery, 6 months after surgery
measure: Attachment level
timeFrame: baseline, after surgery, 1 month after surgery, 6 months after surgery
measure: Colorimetric integration
timeFrame: 1 month after surgery, 6 months after surgery
measure: Patients related outcome measures
timeFrame: 7 days after surgery, 14 days after surgery, 1 month after surgery, 6 months after surgery
measure: Microcirculation of the grafted area
timeFrame: before surgery, after surgery, 7 days after surgery, 14 days after surgery, 1 month after surgery, 6 months after surgery
measure: Morphology of the grafted area
timeFrame: 1 month after surgery or 2 months after surgery or 4 months after surgery or 6 months after surgery
measure: Revascularization and reinnervation of the grafted area
timeFrame: 1 month after surgery or 2 months after surgery or 4 months after surgery or 6 months after surgery
measure: Full mouth Plaque score
timeFrame: baseline, after surgery, 1 month after surgery, 6 months after surgery
measure: Full mouth Bleeding score
timeFrame: baseline, after surgery, 1 month after surgery, 6 months after surgery
measure: Keratinised tissue width
timeFrame: baseline, after surgery, 1 month after surgery, 6 months after surgery
measure: Bleeding on probing
timeFrame: baseline, after surgery, 1 month after surgery, 6 months after surgery
measure: Modified Plaque index
timeFrame: baseline, after surgery, 1 month after surgery, 6 months after surgery
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Department of Periodontology, University Complutense Madrid, Spain
Study officials:
affiliation: Faculty of Odontology, University Complutense, Madrid, Spain
name: Mariano Sanz Alonso
role: STUDY_CHAIR
affiliation: Faculty of Odontology, University Complutense, Madrid, Spain
name: David Palombo
role: STUDY_DIRECTOR
References:
citation: Chappuis V, Araujo MG, Buser D. Clinical relevance of dimensional bone and soft tissue alterations post-extraction in esthetic sites. Periodontol 2000. 2017 Feb;73(1):73-83. doi: 10.1111/prd.12167.
citation: Johnston WM, Kao EC. Assessment of appearance match by visual observation and clinical colorimetry. J Dent Res. 1989 May;68(5):819-22. doi: 10.1177/00220345890680051301.
citation: McLean TN, Smith BA, Morrison EC, Nasjleti CE, Caffesse RG. Vascular changes following mucoperiosteal flap surgery: a fluorescein angiography study in dogs. J Periodontol. 1995 Mar;66(3):205-10. doi: 10.1902/jop.1995.66.3.205.
citation: Melzack R. The short-form McGill Pain Questionnaire. Pain. 1987 Aug;30(2):191-197. doi: 10.1016/0304-3959(87)91074-8.
citation: Perotto S, Romano F, Cricenti L, Gotti S, Aimetti M. Vascularization and Innervation of Connective Tissue Grafts in the Treatment of Gingival Recessions: A Histologic and Immunohistochemical Study. Int J Periodontics Restorative Dent. 2017 Jul/Aug;37(4):551-558. doi: 10.11607/prd.3020.
citation: Rojo E, Stroppa G, Sanz-Martin I, Gonzalez-Martin O, Alemany AS, Nart J. Soft tissue volume gain around dental implants using autogenous subepithelial connective tissue grafts harvested from the lateral palate or tuberosity area. A randomized controlled clinical study. J Clin Periodontol. 2018 Apr;45(4):495-503. doi: 10.1111/jcpe.12869. Epub 2018 Feb 23.
citation: Sanz-Martin I, Encalada C, Sanz-Sanchez I, Aracil J, Sanz M. Soft tissue augmentation at immediate implants using a novel xenogeneic collagen matrix in conjunction with immediate provisional restorations: A prospective case series. Clin Implant Dent Relat Res. 2019 Feb;21(1):145-153. doi: 10.1111/cid.12696. Epub 2018 Dec 3.
citation: Tatarakis N, Gkranias N, Darbar U, Donos N. Blood flow changes using a 3D xenogeneic collagen matrix or a subepithelial connective tissue graft for root coverage procedures: a pilot study. Clin Oral Investig. 2018 May;22(4):1697-1705. doi: 10.1007/s00784-017-2261-5. Epub 2017 Oct 27.
citation: Thoma DS, Zeltner M, Hilbe M, Hammerle CH, Husler J, Jung RE. Randomized controlled clinical study evaluating effectiveness and safety of a volume-stable collagen matrix compared to autogenous connective tissue grafts for soft tissue augmentation at implant sites. J Clin Periodontol. 2016 Oct;43(10):874-85. doi: 10.1111/jcpe.12588. Epub 2016 Aug 12.
citation: Thoma DS, Naenni N, Figuero E, Hammerle CHF, Schwarz F, Jung RE, Sanz-Sanchez I. Effects of soft tissue augmentation procedures on peri-implant health or disease: A systematic review and meta-analysis. Clin Oral Implants Res. 2018 Mar;29 Suppl 15:32-49. doi: 10.1111/clr.13114.