Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000125123
Ethics application status
Approved
Date submitted
11/01/2019
Date registered
29/01/2019
Date last updated
29/01/2019
Date data sharing statement initially provided
29/01/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Ridge preservation in prevention of sinus augmentation
Scientific title
Ridge preservation in prevention of sinus augmentation: comparison between extraction alone and extraction with ridge preservation in individuals undergoing extraction of maxillary second premolars, first molars and/or second molars
Secondary ID [1] 296995 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
sinus pneumatisation 310966 0
alveolar ridge resorption 310967 0
Condition category
Condition code
Oral and Gastrointestinal 309627 309627 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Musculoskeletal 309872 309872 0 0
Other muscular and skeletal disorders
Respiratory 309873 309873 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following enrolment, ridge preservation treatments are assigned randomly via computer-generated numbers. Group allocation is concealed in an opaqued envelope which is opened immediately after extraction. Participants are randomly allocated into two ridge preservation groups:
1/ Grafting group - tooth extraction with ridge preservation with large particles (1 to 2mm) of Bio-Oss or Bio-Oss Collagen and Bio-Gide® determined by clinical preference
2/ Control group consists of participants that underwent extraction without a ridge preservation procedure.

After a pre-procedural rinse with 0.2% chlorhexidine mouth rinse and administration of local anaesthesia with 4% articaine plus epinephrine (1:100,000), tooth extraction is performed by a single clinician with great care to preserve the buccal bone plate and the surrounding soft and hard tissues. For multi-rooted teeth, roots are sectioned and removed separately to minimise damage to the bony cortex and inter-radicular bone. In all cases, extraction is performed without elevating a mucoperiosteal flap.

After tooth extraction, the socket is carefully debrided and irrigated with sterile saline. The integrity of the buccal cortex is inspected visually under magnification with a probe and is recorded as ‘intact’, ‘completely absent’ or ‘presence of dehiscence or fenestrations’. Participants are excluded if more than 50% of the buccal bone height is absent. The participants are then randomly assigned to grafting or control group according to an opaque, concealed, continuously numbered randomisation envelope.

Sockets in grafting group are grafted with large Bio-Oss® granules (particle size 1-2mm) or Bio-Oss collagen blocks. To ensure the sockets are filled to the apical region, each root-alveolus of multi-rooted teeth is filled individually. Sufficient material is placed until the graft materials are about 1mm above the alveolar crest. In all test sites, no attempt to obtain primary closure is made. The graft materials are completely covered by a double layer of Bio-Gide® membrane with the marginal soft tissue of the sockets slightly undermined to receive the membrane without mobilisation of the soft tissue to achieve primary closure. Using a 4/0 non-resorbable, monofilament polypropylene suture (Prolene®, Ethicon), a ‘hidden-X’ suture technique is used. In control sites, sockets are left open for spontaneous healing. Intra-operative complications and adverse events during extraction and ridge preservation procedures, such as buccal bone fracture, need for surgical extractions, oro-antral communication and intra-operative bleeding requiring intervention, are recorded.

A postoperative regimen of oral tablets amoxicillin 500 mg three times daily for seven days (or 150 mg clindamycin oral tablets four times daily for seven days if the patient is allergic to penicillin) is prescribed, paracetamol 500mg and ibuprofen 150mg is taken as required, for seven days. Participants are instructed to avoid rinsing and spitting for the first 24 hours. After that, participants are advised to use 0.2% chlorhexidine mouthwash for rinsing twice daily and to avoid brushing directly on the surgical site until complete gingival closure occurred. Participants are also advised to avoid chewing on the operated side and to maintain a soft diet for two weeks. Both oral and written postoperative care instructions are given. No removable appliances are used, and the sockets are left to heal undisturbed.

All participants are reviewed on a weekly basis during the first month of healing. At the two-week review, participants will be interviewed to assess adherence to the post-operative care and any postoperative complications are recorded including wound dehiscence, loose graft material, wound infection (tenderness on palpation, swelling and suppuration), extra-oral bruising, oedema and other signs of morbidity. In the test groups, sutures are removed after two weeks. All participants are reviewed at four months clinically and a post-operative CT scan is taken to analyse alveolar ridge height at the site of tooth extraction and sinus volume.


All clinical measurements are performed by a single examiner blinded to the group assignment. The following clinical parameters are recorded:
1. Patient’s age and gender
2. Number and location of the teeth present in posterior maxilla: first and second premolars, first, second and third molars

3. Number and location of the tooth or teeth extracted in the posterior maxilla: first and second premolars, first, second and third molars

4. Reason for the extraction: periodontal, endodontic, prosthodontic, restorative (caries, cracked tooth), orthodontic etc.
5. Presence of associated pathologies

Participants had CT scans before and four months after extraction/ridge preservation. The image acquisition settings are developed in consultation with a specialist Dento-Maxillofacial Radiologist, with the aim of using a low radiation dose protocol to minimise dose exposure while achieving clear imaging quality for measurements. All scanning is performed at a single radiology centre with the same machine by dental radiologists (Somatom Perspectives CT Scanner, Siemens Healthineers Australia, manufactured in China, 130KV, 35mAs dose-modulated exposure, 0.6mm slice thickness, 512x512 image resolution, 150mm FOV). The imaging protocol is standardised to include the occlusal plane of the maxilla teeth and the whole maxillary sinus. The mid-sagittal plane is to be perpendicular to the horizontal plane using vertical and horizontal alignment beams as recommended by the manufacturer. All CT scans are performed with the occlusal plane approximately parallel with the primary X-ray beam during acquisition and with no gantry tilt. The occlusal plane is used as the reference plane for subsequent image reconstruction.

All Digital Imaging and Communications in Medicine (DICOM) CT scans data are imported into a 3D dental implant planning software (Simplant Pro 18.0 Dentsply Implants NV, Research Campus 10 3500 Hasslet Belgium). All data sets are allocated a code number so the identity of the participants is masked to the operator. The same operator performed all data set reconstruction and measurements.

Patient-related outcome measures for pain, bleeding, swelling, bruising and interference with activities of daily living are evaluated using a Visual Analog Scale (VAS). These are assessed on the day of the extraction, at two weeks and four months reviews.

For radiographic assessment, it is not possible to mask the treatment group from the control group on the post-extraction scans due to the presence of the grafting material, however the examiner is blinded to the nature of the treatment group. The protocol for reconstruction of the scans to ensure accurate and reproducible orientation and spatial alignment of the three planes are developed in consultation with an experienced oral and maxillofacial radiologist. A panoramic curve is drawn to bisect the maxillary alveolar ridge, at mid-level between the sinus floor and bony crest on the axial plane. The coronal and sagittal planes are then positioned to place the tooth/extraction site in the middle of the ridge. Specifically, axial slices are assessed to identify the slice which displays the mid-ridge parallel to the long axis of the tooth in the mesio-distal and transverse dimensions. The mid-sagittal and the mid-coronal bisecting lines are then identified on this axial slice. To perform the measurements, each extraction site is considered separately and evaluated in the coronal section corresponding to the centre of the extraction/edentulous site.

Bone heights (measured in mm) before and after extraction/ridge preservation are measured at the mid-section of the alveolar ridge where both the coronal and sagittal planes intersect using the linear measurement tool:
1. Pre-extraction mid-ridge height
2. Post-extraction mid-ridge height
3. Pre-extraction buccal-bone height
4. Post-extraction buccal-bone height
5. Pre-extraction palatal-bone height
6. Post-extraction palatal-bone height

The difference between the post- and pre-extraction ridge height measurements determined the change in ridge heights over four months.
Sinus volume determination is performed via a segmentation technique using the Simplant software. Data sets are excluded if significant sinus opacification or mucosal thickening prevented the ability to perform the masking or segmentation function in Simplant. A mask is initially created to highlight the air-filled cavities, followed by the use of a segmentation tool to manually define the entire volume of the maxillary sinus cavity. This allowed the software to automatically calculate the sinus volume in cubic centimetres. The difference between post- and pre-extraction sinus volume determined the change in sinus volume over four months. The need for sinus augmentation is determined based on the mid-ridge height on the post-extraction CT scan. Lateral sinus augmentation would be required when the residual mid-ridge height is <5mm.
Intervention code [1] 313271 0
Treatment: Surgery
Comparator / control treatment
Extraction without a ridge preservation procedure.
Control group
Active

Outcomes
Primary outcome [1] 318584 0
Vertical ridge height in the posterior maxilla after extraction will be measured by CT scans and compared between control and treatment group
Timepoint [1] 318584 0
4 months (before vs 4 months after extraction)
Primary outcome [2] 318585 0
change in maxillary sinus volume after extraction will be measured by CT scans and compared between control and treatment group

Timepoint [2] 318585 0
4 months (before vs 4 months after extraction)
Primary outcome [3] 318586 0
Evaluate the need for sinus augmentation in sites following extraction with or without ridge preservation.
The need for sinus augmentation is determined based on the mid-ridge height on the post-extraction CT scan. Lateral sinus augmentation would be required when the residual mid-ridge height is <5mm.
Timepoint [3] 318586 0
4 months (before vs 4 months after extraction)
Secondary outcome [1] 365444 0
histological and histomorphometric analysis of core sample from extraction sites. at 4 months: one histologic sample will be harvested from the extraction site during implant placement. A bone core will be retrieved from the center of each grafted socket by means of a trephine bur and process for histological and histomorphometric analysis. The sections will be analyzed by a single examiner blinded to the type of treatment. The following parameters are measured as percentages of the total sample area: proportion of new bone, proportion of residual graft material, mineralized fraction, and proportion of connective tissue plus bone marrow.
Timepoint [1] 365444 0
4 months after extraction
Secondary outcome [2] 365445 0
patient related outcome measure (pain) assessed using the Visual analog scale of 1 to 10.
Timepoint [2] 365445 0
immediately after extraction, 2 weeks and 4 months after extraction
Secondary outcome [3] 366184 0
patient related outcome measure (bleeding) assessed using the Visual analog scale of 1 to 10.
Timepoint [3] 366184 0
immediately after extraction, 2 weeks and 4 months after extraction
Secondary outcome [4] 366185 0
patient related outcome measure (swelling) assessed using the Visual analog scale of 1 to 10.
Timepoint [4] 366185 0
immediately after extraction, 2 weeks and 4 months after extraction
Secondary outcome [5] 366186 0
patient related outcome measure (bruising) assessed using the Visual analog scale of 1 to 10.
Timepoint [5] 366186 0
immediately after extraction, 2 weeks and 4 months after extraction

Eligibility
Key inclusion criteria
• 20 years of age or over

• Extraction of maxillary second premolars, first molars and/or second molars

• Vertical bone height from alveolar bone crest to maxillary sinus floor of 6 - 8mm as measured on a CT scan
• All indications for extraction (periodontal, orthodontic, endodontic and restorative)
Individuals with chronic periodontitis were initially treated and subsequently enrolled in a supportive maintenance program prior to recruitment into the study.
Minimum age
20 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Pre-extraction alveolar bone height <5mm or >8mm or if more than 50% of the buccal bone wall is missing or damaged after extraction
• Uncontrolled or untreated periodontal disease
• Any systemic medical condition which is a contraindication for dentoalveolar surgery or interferes with normal wound healing
• Currently pregnancy or lactation at the time of recruitment

• History of smoking, alcoholism or chronic drug abuse
• History of malignancy, radiotherapy, or chemotherapy for a malignancy in the past five years
• Taking long-term steroids, bisphosphonates, chemotherapeutic or require antibiotic prophylaxis
• Significant soft tissue thickening, sinus opacification or pathology in the sinus of interest
• Extraction of upper third molars only
• Inability to consent to participation in the study and/or to accept the proposed treatment plan

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Group allocation is concealed in an opaqued envelope which is opened immediately after extraction.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Following enrollment, ridge preservation treatments are assigned randomly via computer-generated numbers.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis
Descriptive statistics (means, percentage change and standard deviations) are performed for each group to summarise the following outcome variables before and four months after extraction/ridge preservation for each treatment group: mid-ridge, buccal and palatal bone heights, sinus volume and visual analog scale scores for patient related outcome measures. The intragroup differences for changes in vertical ridge dimensions before and four months after extraction/ridge preservation are determined by paired t test. For intergroup analysis, the mean changes in vertical ridge dimensions and sinus volume over four months are compared between the ridge preservation groups and the control group using paired t test. The significance level is set at 0.05. Statistical analysis was conducted using IBM SPSS Statistics, Version 25.0.0 (IBM Corporation 2012(c), Aarmonk, NY, USA). 

The need for sinus augmentation procedures for placement of a standard-length implant based on the residual mid-ridge height four months after extraction is determined at site level based on the criteria in Table 1 and descriptively presented for each case.

Intra-examiner reliability for measurement of mid-ridge height and sinus volume pre- and post-operative measurements for both control and treatment groups was calculated by repeating the measurement procedures over a twoweek interval. Intra-rater class correlation coefficient (ICC) was used to determine intra-rater reliability for the following variables. ICC for pre-extraction mid-ridge height was 0.987 (0.960, 0.996); post-extraction mid-ridge height was 0.998 (0.995, 0.999); and sinus volume was 0.996 (0.984, 0.999).

To evaluate the sample size required for a future clinical trial, two sample size calculations were performed using PS Power and Sample Size Calculations (Version 3.0, 2009) based on the results for changes in sinus volume and mid-ridge height.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
17/03/2017
Date of last participant enrolment
Anticipated
1/01/2021
Actual
Date of last data collection
Anticipated
31/05/2021
Actual
Sample size
Target
50
Accrual to date
13
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 301571 0
Commercial sector/Industry
Name [1] 301571 0
Geistlich Pharma Australia
Country [1] 301571 0
Australia
Primary sponsor type
University
Name
University of Queensland School of Dentistry
Address
288 Herston Rd, Herston QLD 4006
Country
Australia
Secondary sponsor category [1] 301266 0
University
Name [1] 301266 0
Griffith University School of Dentistry and Oral Health
Address [1] 301266 0
Griffith University School of Dentistry and Oral Health
Gold Coast campus
Griffith University QLD 4222
Australia
Country [1] 301266 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302298 0
University of Queensland Human Ethics Research Office
Ethics committee address [1] 302298 0
Ethics committee country [1] 302298 0
Australia
Date submitted for ethics approval [1] 302298 0
Approval date [1] 302298 0
24/04/2018
Ethics approval number [1] 302298 0
2018000825
Ethics committee name [2] 302302 0
Griffith University Human Research Ethics Committee
Ethics committee address [2] 302302 0
Ethics committee country [2] 302302 0
Australia
Date submitted for ethics approval [2] 302302 0
Approval date [2] 302302 0
16/03/2017
Ethics approval number [2] 302302 0
2016/923

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89742 0
Dr Lisetta Lam
Address 89742 0
Brisbane City Periodontics and Implants
11/141 Queen St, Brisbane City QLD 4000
Country 89742 0
Australia
Phone 89742 0
+61 403945451
Fax 89742 0
Email 89742 0
[email protected]
Contact person for public queries
Name 89743 0
Lisetta Lam
Address 89743 0
Brisbane City Periodontics and Implants
11/141 Queen St, Brisbane City QLD 4000
Country 89743 0
Australia
Phone 89743 0
+61 403945451
Fax 89743 0
Email 89743 0
[email protected]
Contact person for scientific queries
Name 89744 0
Lisetta Lam
Address 89744 0
Brisbane City Periodontics and Implants
11/141 Queen St, Brisbane City QLD 4000
Country 89744 0
Australia
Phone 89744 0
+61 403945451
Fax 89744 0
Email 89744 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.