Primary stability of dental implants stabilized by Tetranite adhesive
Research type
Research Study
Full title
A prospective human clinical study to assess primary stability and change in stability by resonance frequency analysis of immediately inserted and restored dental implants using Tetranite Stabilization Material
IRAS ID
272223
Contact name
Michael Norton
Contact email
Sponsor organisation
LaunchPad Medical Inc
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary
To date dental implants have relied on mechanical fixation of a threaded or press fit implants in bone to achieve primary stability. The degree of primary stability is claimed to influence implant success, especially in the circumstance of immediate placement of the implant in an extraction socket when immediate functional restoration of the implant is planned. However with limited bone volume and often compromised bone quality it can be difficult to achieve the desired primary stability considered an essential prerequisite for implant success under these circumstances. This study is established to evaluate the immediate and subsequent stability of implants placed in patients requiring extraction of one or more teeth, inserted directly into the extraction sockets and restored with temporary acrylic crowns, but which benefit from a new class of bone adhesive, Tetranite® Stabilization Material (TN-SM). Stability will be assessed at time of implant placement and immediately after final set of the TN-SM as well as one week, one month, 3 months, 6 months and one year post-insertion of the implant, by means of RFA to record the change in ISQ. In addition baseline cone beam CT scans will be taken to plan the case, according to normal practice, and specifically to measure the width of the alveolar socket and to compare that with the width of the alveolar bone 1 year after implantation, to evaluate the ability of TN-SM to support bone maintenance, as has been demonstrated in the canine model. All implants will continue to be followed-up to include a 1-year review from time of implant placement, in order to determine implant survival at that time point, and then annually thereafter as part of the clinic's routine follow-up program.
Summary of Results
Study Overview
The purpose of this report is to summarize the final results of the clinical study: A prospective human clinical study to assess primary stability and change in stability by resonance frequency analysis of immediately inserted and restored dental implants using Tetranite® Stabilization Material.
This clinical trial (CI/2019/0057) was approved on March 9, 2020. This report includes data collected on 14 dental implants stabilised with Tetranite® Stabilization Material (TN-SM) in 11 subjects. Data for this report includes all study data collected.
Tetranite® Stabilization Material bonds dental implants to bone in applications where additional mechanical stabilisation is required at the time of placement. Its purpose is to augment primary stability of dental endosseous implants inserted into sites that lack adequate primary stability. Tetranite is resorbed over several months while being replaced with new bone without compromising implant stabilisation.The aim of this clinical investigation is to demonstrate the safety and efficacy of the use of TN-SM to allow clinical study of the TN-SM device in a greater number of patients. It is also an aim of this study to test performance characteristics and capabilities of study designs, measures, procedures, recruitment criteria, and operational strategies that are under consideration for use in a larger subsequent study. This is the first time this product has been used in human subjects in the UK. This study is intended to provide an understanding of technique and the product refinements that may be necessary.
The primary endpoint of this study is sufficient bone-to-implant interfacial stiffness of the implant stabilised by TN-SM. Interfacial stiffness is measured by resonance frequency analysis (RFA), expressed as mean implant stability quotient (ISQ) at 1-year post TN-SM device and implant placement. For the study to be considered successful, the lower bound of the one-sided 97.5% confidence interval for the mean ISQ should exceed the clinical threshold of 60.
Based on the results from this study as discussed below, a formulation modification of TN-SM has been in development at RevBio. The learnings from the current pilot study have indicated that a modified formulation could help improve soft tissue healing and the long-term outcomes for implant stabilisation. RevBio has started an additional pilot study to test the clinical performance of the modified formulation (DVAL 22004).
Subject Enrollment
A total of 11 subjects, with 14 study-related dental implants were enrolled in this study. The investigator enrolled patients requiring tooth extraction who desire a replacement with a dental implant. In addition to giving voluntary informed consent and being a minimum of 20 years of age, subjects must have also met the following inclusion criteria:
• Subjects who require a single anterior maxillary tooth extraction and desire a replacement with a dental implant and immediate temporary crown. Candidate subjects may require more than one extraction, and all sites will be considered for inclusion in the study;
• Subjects must have opposing dentition (natural teeth, fixed or removable restorations);
• Subjects must be committed to the study and the required follow-up visits;
• Subjects must be ASA I or ASA II;
• Subjects who present with a sound bony housing with a visible buccal plate evident at the crest and fenestrations or dehiscences limited to <5.0mm diameter on a cone beam CT;
• There must be sufficient bone height crestal to critical anatomical structures, i.e., the piriform foramen, and maxillary sinus, to safely place a dental implant within the bone contours. Extraction sockets should be able to accommodate an implant > 9.0mm in length;
• Anatomical conditions must be present to allow an implant crown restoration to be placed at the candidate site, e.g., sufficient interocclusal space, incisal Class1 or Class 2 Div 1 relation, appropriate angulation of the ridge, etc.Patients with multiple tooth extractions were considered for the study, and study inclusion of all sites was based on which sites meet the Extraction Site Enrollment Criteria. If multiple sites met the criteria, they all received the test device. Patients were excluded from the study for issues that could affect intraoral or bone healing such as periodontal disease or fibrous dysplasia. A full list of exclusion criteria can be found in the protocol.
Medical and dental history was obtained for each patient during screening and updated as needed during subsequent study visits.
Upon extraction of the tooth, subjects were only enrolled if the extraction site met the following criteria:
• There is at least 2mm of apical bone below the apex of the extraction socket for positive seating of the implant;
• Any implant site in which placement of the selected implant leaves an HDD > 2mm in the buccal direction between the implant surface and the labial plate at the most coronal aspect of the extraction socket.Extraction sites were excluded for any of the following reasons:
• Any site into which the implant is not or cannot be placed during the same visit as the extraction.
• Any implant site where there is a dehiscence or fenestration of buccal or lingual plates of bone greater than 5mm in any direction;
• Any implant site in which placement of the selected implant leaves an HDD greater than 5mm in any direction between the implant surface and the most coronal aspect of the osteotomy;
• Any site which provides primary implant stability after seating as demonstrated by insertion torque of greater than or equal to 15Ncm;
• Any implant site where, during the osteotomy preparation, a submarginal perforation developsSubjects were considered enrolled after the extraction site-specific inclusion and exclusion criteria were met.
The protocol planned for a total of 15 enrollments in this study. However, due to the preliminary study results with 4 implant failures in the enrolled subjects, a new study was started with a modified formulation of Tetranite. At that time, the enrollment in this study ceased. 11 of the expected subjects were enrolled.
Study Results
The first of the 11 subjects was enrolled on July 15, 2020. Since then, eight of the 11 subjects have gone through the enrollment, qualification, surgical, post-operation follow-up, stability monitoring. Definitive crown placement and 3-, 7-, and 12- month follow-up visits.The remaining three subjects not in the follow-up stage have exited the study due to implant failures. In most cases of implant failure, the subjects presented with localised infection associated with exposed adhesive at the site of the implant. Upon investigation, the implants were found to have some mobility and were typically removed and categorized as an implant failure. A total of four implant failures occurred prior to definitive crown placement. Three of those four occurred in patients with only one study-related implant. One implant failure occurred in a subject with two total study-related implants. Only one of the implants failed and the remaining implant is still stable. Therefore, the subject is still enrolled in the study. All implant failures and associated events were documented as adverse events.
RFA measurements expressed as mean ISQ were taken immediately before and after TN-SM device placement and at the 3-, 7-, and 12-month follow-ups. The mean ISQ was 59.1 (58.3 buccolingually (BL) and 59.9 mesiodistally (MD)) before TN-SM device placement. Immediately after TN-SM device placement, the mean ISQ was 71.9 (71.3 BL and 72.5 MD). The mean ISQ at 3-, 7-, and 12- months post-device placement was 71.0 (69.8 BL and 72.2 MD), 78.9 (77.8 BL and 79.9 MD), and 80.3 (79.4 BL and 81.2 MD), respectively.
The primary endpoint of this study is sufficient bone-to-implant interfacial stiffness of the implant stabilised by TN-SM. For the study to be considered successful, the lower bound of the one-sided 97.5% confidence interval for the mean ISQ should exceed the clinical threshold of 60 at 1-year post TN-SM device and implant placement. The ISQ at 1-year post TN-SM device and implant placement had a lower bound of the one-sided 97.5% confidence interval for the mean of 77.6 (lower bound of 76.2 for buccolingual measurements and 78.8 for mesiodistal measurements). This exceeds the clinical threshold of 60. Therefore, the primary endpoint of this study has been met.
Further, the data shows an increase in the ISQ before and after TN-SM device placement. The mean ISQ was also shown to remain above the clinical threshold of 60 for at least 12-months post-device placement. This indicates that the TN-SM device may provide sufficient bone-to-implant interfacial stiffness of the implant when stabilised by TN-SM.
Future Plans
RevBio is continuing the additional pilot study in the UK of the modified Tetranite formulation, known as TN-ISM. To date, there has been one implant failure with 5 enrollments in that study (minimum of one month follow-up). The sponsor plans to pursue a pivotal study of TN-ISM pending the results of the TN-ISM pilot study.
REC name
London - Stanmore Research Ethics Committee
REC reference
20/LO/0079
Date of REC Opinion
9 Mar 2020
REC opinion
Further Information Favourable Opinion