This is a single centre non-inferiority adaptive randomised controlled clinical trial. The primary aim of this study will be:
To assess the clinical composite outcome (incidence of complications and percentage of vertical bone gain) of vertical alveolar bone grafting procedures in patients with vertical ridge deficiencies prior to dental implant placement, using a mix of autogenous and xenogenic particulate bone materials in combination with four different barrier membranes (Titanium (Ti)-Reinforced d-Polytetrafluoroethylene (PTFE) membrane \[control group\], Ti-Reinforced e-PTFE Membrane, 3D printed Ti-mesh and Reinforced PTFE Mesh (RPM)).
Secondary aims are:
* To assess and compare soft tissue wound healing and vascularization using Laser Doppler Flowmetry (LDF) between tests and control.
* To assess and compare gingival microvasculature and structure in vivo using Optical Coherence Tomography (OCT) between tests and control.
* To compare prevalence of the need for further bone grafting at the time of implant placement between tests and control.
* To compare prevalence of the need of soft tissue grafting at second stage surgery between tests and controls.
* To assess and compare patient reported outcomes using the EuroQol five-dimension (EQ-5D-5L) scale and the short-form Oral Health Impact Profile (OHIP-14) between tests and control.
* To assess and compare histomorphometry and histochemistry analyses of core biopsies obtained from a sample of 5 participants from each group before implant placement between tests and control.
Patients in need of vertical ridge augmentation prior to dental implant placement will be recruited to take part in this study and will be randomised into one of the following groups receiving different interventions:
1. VRA using a 50/50 particulate bone mix (xenograft+ autograft) + Ti-Reinforced d- PTFE membrane (Positive Control)
2. VRA using a 50/50 particulate bone mix (xenograft+ autograft) + Ti-Reinforced e-PTFE membrane (Test 1).
3. VRA using a 50/50 particulate bone mix (xenograft+ autograft) + 3D printed Titanium mesh (Test 2).
4. VRA using a 50/50 particulate bone mix (xenograft+ autograft) + Reinforced PTFE mesh (Test 3)
One-hundreds and forty-eight (148) participants meeting inclusion/exclusion criteria and who consent to this study will undergo a baseline visit assessment (visit 2) in which they will have a comprehensive oral assessment, radiographic assessment of alveolar defect using Cone Beam CT and supportive periodontal therapy. After randomisation to either Tests (1-3) or Control Groups, each group will undergo a VRA procedure as randomised (visit 3). All patients will be re-examined at 1, 3, 7, 15, 30, 60 and 120 days (visits 4-10, respectively) after the surgical augmentation. At each assessment, clinical examination, soft tissue imaging measures and saliva collections will be performed. Additionally, supportive periodontal therapy will be provided to all participants at the 120 days post augmentations visit. All participants will then undergo dental Implants placement after 180 days (visit 11). Participants will then be followed at 7, 15, 30,90, 120, 180 and 365 days (visits 12-18) after dental implant placement. The 90 days post implantation visit will include supportive periodontal therapy while the 120 days visit will involve the placement of dental implant prosthetic components for all participants.
Statistical methodology and analysis:
Primary and secondary outcomes analysis:
Continuous data are displayed as mean and standard deviation whilst categorical variables will be reported as percentages and prevalence. All participants randomized to test or control will be included in final analyses. Analysis will be performed using last observation carrying forward and as intent to treat population. Secondarily, per protocol analysis will also be performed. Data will be entered in an electronic spreadsheet and checked/proofed for any errors. All data will be loaded in the appropriate software for analysis. The primary outcome assessment will be assessed by analysis of co-variance model. Age, gender, body mass index and ethnicity will be included as principal covariates. Pair-wise comparison and between groups differences will be calculated using Tukey corrections.
All secondary endpoints will be analysed in a similar fashion. Significance will be set to be at p ≤ 0.05. Adverse events analysis will also be performed between study groups at study visits. Serial changes in imaging variables will be analysed with analysis of variance for repeated measures using a conservative F-test (Greenhouse-Geisser correction). If a treatment by time interaction will be found, pair-wise comparisons will be performed (Bonferroni-Holm adjustment).
Sensitivity and other planned analyses:
In this trial, investigators will perform some types of the sensitivity analysis, including non-statistical and statistical analyses. The sensitivity analysis that investigators will be including are impact of non-compliance/protocol deviation, impact of missing data, impact of competing risk in analysis of composites outcomes, impact of baseline imbalance, and finally, related to statistical analysis is impact of different assumptions underlying statistical model. The option plan for the condition related to non-compliance/protocol deviation are intention-to-treat (ITT) analysis; as per protocol analysis; and as-treated analysis.
