Clinical trial NCT04286334: Three-dimensional Bone Regeneration Using Custom-made Meshes With and Without Collagen Membrane
Official title: Three-dimensional Bone Regeneration Using Custom-made Meshes With and Without Collagen Membrane: Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Surgical Procedure, Unspecified
Soft Tissue Infections
Surgical Wound Dehiscence
Bone Density
Bone Loss in Jaw
Lead sponsor: GBR Academy
Sponsor class: NETWORK
First posted: 2020-02-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The presence of alveolar ridge deficiencies is considered major limitation to achieve an implant-prosthetic restoration with high aesthetics and stability over time. Guided Bone Regeneration (GBR) can be considered an effective solution for bone augmentation. The most advanced technology of GBR is the customized titanium mesh, which is developed with a fully digital work flow system. The aim of this study is to evaluate complications and bone augmentation rates after GBR, based on customized meshes with or without collagen membranes.

After ethical committee approval, 30 patients with horizontal and/or vertical bone defects were enrolled and treated according to the study protocol. During reconstructive surgery (T0), patients were randomly divided into two study groups: 15 patients were treated by means of a custom-made mesh without collagen membrane (Group A - Control Group), while 15 patients were treated by means of a custom-made titanium mesh with a collagen membrane (Group B - Test Group). All sites were grafted with a mixture 50:50 of autogenous bone and xenograft and primary closures of surgical sites were obtained to ensure a submerged healing of the meshes. After 6 months (T1), re-entry surgery was completed to remove the meshes, evaluate the augmented volume and to place implants in the augmented sites. After 3 months (T2), soft tissue management was accomplished with implant exposure and a connective tissue graft, before prosthetic restoration (T3). Data collection included surgical and healing complications, planned bone volume (PBV) and reconstructed bone volume (RBV), pseudo-periosteum type, bone density, implant success, and crestal bone loss. A statistical analysis of recorded data was performed to investigate any statistically significant differences between the study group and statistical significance was set at a=0.05.

Detailed description: The rationale of the study is based on the fact that manual and intraoperative modeling of an osteosynthesis mesh is an employee operator and even in the case of very experienced operators it is always difficult, inaccurate and slow. The use of this pre-modeled and pre-fabricated custom-made mesh with bevel margins and three-dimensionally morphology adapted to the bone defect, would allow for a congruous bone regeneration reducing the operating times, the risks linked to the mesh trauma, and the discomfort for the patient. The collagen membrane in association with titanium, based on the principles of guided bone regeneration (GBR), would make it possible to increase bone gain and reduce the percentage of early and late exposure of the mesh.

This study aims to evaluate, in cases of maxillary and mandibular atrophies characterized by a vertical and / or horizontal resorption of the alveolar bone, the percentage of complications (intra- and post-operative) after bone regeneration using custom-made mesh with or without collagen membrane.

The primary objective of this study is to evaluate the non-inferiority of technique B (custom-made mesh - without membrane) compared to technique A (custom-made mesh - with membrane) in the incidence of complications.

Secondary objectives include evaluation of the missing bone volume (lacking bone volume or LBV), reconstructed bone volume (reconstructed bone volume or RBV) with respect to planned bone volume (planned bone volume or PBV), histological and histomorphometric analysis at the time removal of the mesh and peri-implant bone resorption, due to the functional loading of the implants, at 12 months of follow-up.

Other objectives include the qualitative evaluation of bone regeneration by histological and histomorphometric analysis upon removal of the mesh; and the evaluation of peri-implant bone resorption, due to the functional loading of the implants, at 12 months of follow-up.

This is a clinical trial which is promoted by Prof. Claudio Marchetti and the University Hospital of Bologna - Policlinico Sant'Orsola Malpighi. The study is designed as a pilot, randomized, monocentric, independent, parallel-group clinical trial, in which the variables will be analyzed prospectively.

The study will have a selection and enrollment period of approximately 12 months; a treatment period of about 12 months. As a result, the overall duration of the study will be around 24 months.

In the two-year period 2017/2019 the study will include the treatment of 30 patients, in good general health, suffering from partial edentulism of the maxilla and / or jaw with vertical and / or horizontal resorption of the alveolar bone, which require prosthetic rehabilitation supported by implants to improve function and aesthetics of edentulous areas.

Patients will be divided into 2 study groups and assigned to each study group based on the previously computer-generated randomization sequence: 15 patients (group A, control) will be treated by bone regeneration with custom-made mesh without a collagen membrane. 15 patients (group B, test) will be treated by bone regeneration with custom-made mesh with collagen membrane.

In the following table, the 3 treatment phases: The first phase (T0) involved bone regeneration with a custom-made mesh (group A) and with collagen membrane (group B); the second one (T1), subsequently, after 6 months: will forsee the removal of the regeneration device and the insertion of the implants; the thirt (T2), 3 months after the aforementioned, will forsee the final functional loading of the implants, with a consequent follow-up of the regenerated bone.

All the materials and tools that will be used in the study are CE certified (with the exception of the custom-made mesh which, as a custom-made device, does not require CE certification) and have already been used in the normal care path for patients who have undergone bone regeneration. Moreover, the control visits and the radiological investigations of the data foreseen by the aforementioned protocol will be collected; They will be summarized in the case report form (CRF), and are those that characterize the normal care path of patients undergoing necessary bone regeneration for prosthetic implant rehabilitation when the bone quantity is insufficient.

The primary objective of this study is to evaluate the non-inferiority of technique B (digital technique) compared to technique A (traditional technique) in the incidence of complications.

The Secondary objectives include: assessment of patient and operator benefits, reconstructed bone volume (RBV) compared to planned bone volume (PBV), histological and histomorphometric analysis of bone quality obtained and peri-implant bone resorption after 12 months of follow-up.

The sample size necessary to support the null hypothesis is 17 subjects for each group. In order to compensate for any protocol deviations or possible drop-outs, the number of patients was increased to 15 per group.

The results obtained in the two study groups will be subjected to descriptive statistical analysis and the differences between groups will be tested by means of appropriate statistical tests for purely exploratory and non-demonstrative purposes.

The patient will be considered as the statistical unit of the analysis, and the statistical significance will be set at α = 0.05.

The collected data will be grouped and summarized with respect to the demographic, anamnestic, and clinical variables of each patient.

Exploratory analyses will be performed using descriptive statistics. The data will be presented both for the intent-to-treat population and for the per-protocol population.

The sample size necessary to support the null hypothesis is 17 subjects for each group. In order to compensate for any protocol deviations or possible drop-outs, the number of patients was increased to 15 per group. The sample size was calculated using dedicated statistical software (STATA, StataCorp LLC) through Pearson's chi-squared test, guaranteeing a level of significance of 95% and a power of 80%.

Eligibility criteria: Adult patients, over the age of 18, in good general health.

* Patients with partial edentulism of the maxilla or mandible, with a 2mm minimum to a 12mm maximum vertical bone defect, which requires a three-dimensional bone regeneration intervention in order to have a fixed implant supported rehabilitation.
* Obtaining informed consent for experimental treatment and processing the personal data.

Exclusion Criteria:

* Poor oral hygiene,
* Untreated periodontal disease
* Smoking habit\> 10 cigarettes / day;
* Abuse of alcohol or drugs
* Pregnancy
* Patients with odontostomatological infections and / or systemic infections in progress;
* Patient with uncontrolled diabetes mellitus or other metabolic diseases;
* Patients with severe changes in liver and kidney function.
* Patients with confirmed uncontrolled autoimmune disorders.
* Patients subjected radiation therapy in the head or neck region in the last 5 years.
* Patients undergoing immunosuppressive and / or immunocompromised therapy

Primary outcomes:
measure: The rate of healing complications after reconstructive surgery
timeFrame: 6 months
Secondary outcomes:
measure: Level of anxiety of the patient measured with a Visual Analogue Scale (VAS)
timeFrame: Immediately before/after surgery
measure: Pain level of the patient measured on a Visual Analogue Scale (VAS)
timeFrame: Post operative from immediately after surgery to the 14th day after the surgery
measure: Total Number of painkillers taken post-operative
timeFrame: Post operative from immediately after surgery to the 14th day after the surgery
measure: Dosage of painkillers
timeFrame: Post operative from immediately after surgery to the 14th day after the surgery
measure: Limitation in daily functions measured on a Visual Analogue Scale (VAS)
timeFrame: Post operative from immediately after surgery to the 14th day after the surgery
measure: Number of patients' post-operative signs and symptoms
timeFrame: From the 1st day to the 14th day after the surgery.
measure: Discomfort level of the patient using a Post-operative Symptom Severity (PoSSe)
timeFrame: Post operative, measured on 14th day after the surgery]
measure: Level of satisfaction of the patient using a Health-Related Quality of Life (HrQoL)
timeFrame: 6 months and 12 months after the dental prosthesis dental prosthesis has been placed.
measure: Willingness of the patient to undergo the intervention recorded on a Visual Analogue Scale (VAS)
timeFrame: Post operative measured on the 7th day and on the 14th day
measure: Time required for the CBCT analysis and design of the medical device
timeFrame: Pre-operative, 2 weeks before the day of the surgery
measure: Total operative time required for the surgery, measured from immediately before to immediately after the surgery.
timeFrame: During procedure
measure: Total chair time measured from immediately before the surgery to immediately after the surgery.
timeFrame: During procedure
measure: Level of operator satisfaction Measured on a 5 point scale
timeFrame: Immediately after the surgery
measure: Level of operator confidence with the technique
timeFrame: During procedure
measure: Costs related to the technique
timeFrame: Immediately after the surgery
measure: Operator anxiety level recorded on a Visual Analogue Scale (VAS)
timeFrame: From 3 days before the surgery to immediately before the surgery, during the intervention and at the 14th day after the surgery.
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: School of Dentistry - University of Bologna
Study officials:
affiliation: school of dentistry - University of Bologna
name: Giuseppe Corinaldesi, MD, DDS, MS
role: STUDY_DIRECTOR
References: