Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04749953 |
| Other study ID # |
Thomas Starch-Jensen1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2020 |
| Est. completion date |
January 20, 2021 |
Study information
| Verified date |
February 2021 |
| Source |
Aalborg University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Implant placement in the posterior maxilla is compromised due to atrophy of the alveolar
process and maxillary sinus pneumatisation. Bone augmentation is frequently necessary before
or in conjunction with implant placement. The most commonly used method to augment the
posterior maxillary involves maxillary sinus floor augmentation (MSFA) with autogenous bone
graft or bone substitute. Autogenous bone graft harvesting is associated with risk of donor
site morbidity and unpredictable resorption of graft. Thus, bone substitutes alone or in
combination with autogenous bone are used increasingly to simplify the surgical procedure.
Symbios biphasic biomaterial is a resorbable inorganic bone forming material derived from red
algae consisting of 20% hydroxylapatite and 80% β-tricalciumphosphate with osteoconductive
properties. Histologic and radiographic examinations indicate that β-tricalciumphosphate is
slowly resorbed and replaced with bone. MSFA with β-tricalciumphosphate alone or in
combination with autogenous bone or other bone substitutes have demonstrated high implant
survival and new bone.
Symbios xenograft granules is a porcine bone mineral with osteoconductive properties.
Histologic and radiographic examinations indicate that xenograft is a non-resorbable graft
material. MSFA with xenograft alone or in combination with autogenous bone have shown high
implant survival and new bone.
The objective is to test the H0-hypothesis of no difference in implant outcome after MSFA
with autogenous bone graft or in combination with Symbios biphasic biomaterial or Symbios
xenograft. 60 consecutively healthy patients with a missing posterior maxillary tooth/teeth
will be randomly allocated to: 1) MSFA with autogenous bone graft, 2) MSFA with mixture of
50% autogenous bone graft and 50% Symbios biphasic biomaterial 3) MSFA with mixture of 50%
autogenous bone graft and 50% Symbios xenograft. Implants will be inserted simultaneously
with MSFA. Clinical and/or radiographical evaluation using periapical radiographs and Cone
Beam Computer Tomography will be performed preoperatively, immediate postoperatively, before
abutment connection, after prosthetic rehabilitation, and after one year to assess the
treatment outcome and volumetric changes of the augmented area. Outcome include survival of
suprastructures and implants, volumetric stability of graft, peri-implant marginal bone
level, oral health related quality of life, and complications.
Description:
Maxillary sinus floor augmentation (MSFA) is the most frequently used method to enhance the
alveolar bone of the posterior maxilla before or in conjunction with implant placement.
Autogenous bone is considered as the preferred graft material due to its osteoinductive,
osteogenic and osteoconductive characteristics. However, autogenous bone grafts is associated
with risk of donor site morbidity and unpredictable graft resorption. Hence, various bone
substitutes are used increasingly to simplify the surgical procedure by diminishing the need
for bone harvesting. From a clinical and patient perspective, it would be an advantage, if
autogenous bone grafts could partially or totally be replaced with bone substitutes.
Symbios xenograft is a new porcine bone mineral characterized as an anorganic bone matrix
with an interconnecting macro- and microscopic pore structure that supports formation and
in-growth of new bone. Porcine xenograft have previously been used for various augmentation
procedures disclosing new bone formation. Studies comparing autogenous bone graft with
porcine bone alone or a mixture of autogenous bone and porcine bone have demonstrated high
implant survival and new bone.
Synthetic biomaterials including calcium phosphate, calcium sulphate, polymers and bioactive
glass represent a large group of inorganic diverse biomaterials with variating structures,
chemical composition and physical properties. Symbios biphasic biomaterials is a resorbable
inorganic bone forming material derived from red algae consisting of 20% hydroxylapatite and
80% β-tricalciumphosphate. Studies assessing MSFA with β-tricalciumphosphate have
demonstrated that it is a safe grafting material with osteoconductive properties. Histologic
and radiographic examinations indicate that β-tricalciumphosphate is slowly resorbed and
replaced with bone. MSFA with β-tricalciumphosphate alone or in combination with autogenous
bone or other bone substitutes have demonstrated high implant survival and new bone.
The study purpose is to increase our knowledge about MSFA with autogenous bone alone or in
combination with Symbios biphasic biomaterials or Symbios xenograft granules and to
simplified the procedure. Evaluation will include survival of suprastructures and implants,
peri-implant marginal bone level, volumetrical stability of the graft and complications after
an observation period of one year. Furthermore, oral health related quality of life, using
OHIP-14 self-administrated and patient satisfaction using visual analogue scales (VAS), will
be evaluated.
The objective is to test the H0 hypothesis of no differences in 1) Survival of
suprastructures and implants, 2) Volumetrical stability of the graft, 3)Peri-implant marginal
bone level, 4) Implantat stability quotient, 5) Patient-reported outcome measures, and 6)
Biologic and technical complications.
Materials and methods Study population 60 consecutively healthy patients with a missing
posterior maxillary tooth will be included and randomly allocated to: 1) MSFA with autogenous
bone graft alone (control group), 2) mixture of 50% autogenous bone graft and 50% Symbios
biphasic biomaterial (test group I), and 3) mixture of 50% autogenous bone and 50% Symbios
xenograft (test group II). The study will be conducted at the Departments of Oral and
Maxillofacial Surgery, Aalborg University Hospital, Denmark and Oral and Maxillofacial
Surgery and Oral Medicine, Malmö University, Malmö, Sweden.
Patients will be included to the study by using a Facebook posting through the University's
Facebook page, the local dental association website or patients that are referred to the
Departments for treatment of one or more missing teeth in the posterior maxilla. All patients
will be offered participation in the study, if they meet the inclusion criteria. Prior to
patients' first visit, they will receive a notice informing about their rights and informed
consent form will be signed.
Inclusion criteria involves 1) >20 years, 2) Missing one or more posterior maxillary teeth,
3) Residual bone height of the maxillary alveolar process between 3 to 7 mm, 4) Width of the
alveolar process ≥6.5 mm and, 5) Mandibular occluding teeth. Exclusion criteria involves 1)
Contraindications to implant therapy, 2) Full mouth plaque score >25%, 3) Progressive
marginal periodontitis, 4) Acute infection in the area intended for implant placement,
5)Parafunction, bruxism, or clenching, 6) Psychiatric problems or unrealistic expectations,
7) Heavy tobacco use, define as >10 cigarettes per day, and 8)Pregnancy.
The study is approved by the local ethical Committee on Health Research and the Danish Data
Protection Agency and The Ethical Review Board in Lund, Sweden' and will be performed
according to the Declaration of Helsinki on clinical research. All patients will be given
verbal and written information about the study at a clinical visit prior to surgery. Written
informed consent is mandatory for inclusion in the study and will be obtained by the
investigators.
The initial examination of the patient will include 1) Clinical examination and screening of
the parodontal health, 2) Radiographical examination of the residual alveolar bone height
based on CBCT and Orthopantomography, and 3) Patient will fill out the OHIP-14 questionnaire.
The surgical procedure will be performed in local anesthesia. Implant installation and
fabrication of the subsequently prosthetic solution will be performed according to
manufacturer's recommendations. The maxillary sinus wall is exposed by an intraoral marginal
incision from tuber maxillae to the first premolar with a vertical releasing incision. A 1 x
1 cm window to the maxillary sinus is created with metal and diamond burrs maintaining an
intact Schneiderian membrane. The Schneiderian membrane is elevated from the sinus floor as
well as the lateral sinus wall and displaced dorsocranially with blunt dissector. An implant
bed is successively prepared on the top of the alveolar crest following manufactory's
recommendations at 1500 rpm. A straight implant (ASTRA TECH Implant System EV 3.6, 4.2 or
4.8, 13 mm) is inserted with a cover screw. The implant stability quotient is measured for
all inserted implants. A sealed randomization envelope is opened in order to allocate the
patient to: 1) MSFA with particulated autogenous bone graft alone (control group), 2) a
mixture of 50% particulated autogenous bone graft and 50% Symbios biphasic bone graft
material (1.0 mm to 2.0 mm) (test group I), 3) a mixture of 50% particulated autogenous bone
graft and 50% Symbios xenograft granules (1.0 mm to 2.0 mm) (test group II). The autogenous
bone graft is harvested with a curved SafeScraper from the zygomatic buttress area. Specially
prepared stainless steel cups (0.5 cm3 and 1 cm3) are used to estimate 1 cm3 of graft
material for each inserted implant. The graft material will be soaked in autogenous blood
from the surgical site until use. The sinus around the implant is packed with 1 cm3 graft
material. The created window to the maxillary sinus is covered by a Symbios Collagen Membrane
15 x 20 mm. Periosteum and mucosa are sutured with Vicryl 4-0. Minor perforations of sinus
membrane will be covered with a Symbios Collagen Membrane. If the sinus membrane is largely
perforated the procedure will be cancelled, and the patient will be withdrawn from the study.
No provisional restoration is inserted during the healing period. After six months of
healing, the inserted implants in the three treatment groups are exposed via a crestal
incision. Mucosa and periosteum are elevated and the cover screw is removed. The implant
stability quotient is measured for all inserted implants. The implant is rinsed with saline
and a prefabricated healing abutment is placed. The implants are manually tested for mobility
and osseointegration by percussion. Mucosa is adapted and sutured with Vicryl 4-0. The
prosthetic restoration will be initiated three weeks after the healing abutment has been
placed.
Prosthetic restoration will include an individualized abutment and a fixed restoration
performed by experienced prosthodontists with extensive clinical experience with
implant-based prosthetics.
Patients will be scheduled for a postoperative clinical examination at baseline, and one year
after loading. The following parameters will be recorded at each visit 1) Plaque and gingival
index, probing pocket depth, and probing attachment level, 2) Oral health related quality of
life - OHIP-14 and 3) Patient satisfaction (VAS).
Radiographical evaluation will include seven sets of periapical radiographs and CBCT obtained
preoperatively, immediately postoperatively, after abutment connection, at baseline and one
year after loading. To provide blinding of the radiographical evaluation, the CBCT-scans are
coded. Volumetrical changes of the grafts are estimated by point counting and the method
described originally by Cavalieri. To obtain an equivalent starting point for the systematic
uniform random sampling of the CBCT-scans images involving the maxillary sinus, all images
from the neighboring teeth to the implant bed are selected. The first CBCT images after the
distal surface of the anterior neighboring tooth is sampled randomly using a random number
table for each maxillary sinus. Every second CBCT image is selected to ensure an equal mutual
distance between the selected 5-10 images. The original outline of the maxillary sinus before
implant installation is recorded and superimposed on the corresponding images. A point grid
test system is superimposed at random on all images, allowing 100-200 points to hit the graft
of each maxillary sinus. The numbers of intersections over the graft are counted on each
selected image. Cavalieri volume estimation principle is used to estimate the total volume of
the graft.
V = t x a(p) x ΣP
Where V is volume, t is the distance between the sampled images, a(p) is the area associated
with each test point corrected for magnification and ΣP is the total number of points hitting
the graft.
Peri-implant marginal bone changes are evaluated by linear measurements on digital periapical
radiographs and will be done on radiographs obtained at implant placement, baseline, and one
year after loading. The distance from the implant-abutment connection to the marginal bone
level will be measured mesially and distally parallel with the long-axis of the implant.
Data management and analysis including calculation of descriptive statistics are done using
STATA. A power calculation are based on differences in marginal bone level changes preformed
in a previous study involving replacement of a single tooth with 2 different protocols of
implant treatment. The calculation is based on the observed changes in marginal bone level
from insertion of the implant to abutment connection (a change of 0.65 mm and a standard
deviation of 0.65), 17 patients in each group reaches a power of 97% at the 5%-level. With
15% to cover drop-outs, each treatment group should include 20 patients. The statistical
evaluation is performed by analysis of variance. Scheffe´s multiple comparison test is used
post hoc to determine the relative effect of the various graft types. Level of significance
is 0.05.
