Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02337166 |
| Other study ID # |
CEP-HUAM/CCM 21/03 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1/Phase 2
|
| First received |
January 8, 2015 |
| Last updated |
January 12, 2015 |
| Start date |
December 2002 |
| Est. completion date |
August 2013 |
Study information
| Verified date |
January 2015 |
| Source |
Universidade Federal Fluminense |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Brazil: Ministry of Health |
| Study type |
Interventional
|
Clinical Trial Summary
BACKGROUND: Periodontal disease is an infection that results in progressive loss of dental
support, which may lead to tooth loss.. The goal of the present study was to evaluate if
recombinant human Fibroblast Growth Factor type 2 (rhFGF-2) applied in periodontal intrabony
defects in a hyaluronic acid (HA) carrier would enhance the clinical paramenters of
regeneration of the periodontal attachment apparatus and the long-term maintenance of the
results obtained. METHODS: Thirty adult patients were evaluated. Initial treatment consisted
in plaque control measures executed previously to the experimental phase. Two intra-bony
defects in each patient were ramdomly allocated for each of the treatment methods employed.
Control group (n=30) were treated by open debridement with the papilla preservation flaps,
while the text group (n=30) also received a topical application of rhFGF-2/HA in the
intrabony defect. The parameters evaluated were, probing depth (PD), gingival recession
(REC), probing attachment level (PAL) and probing bone level (PBL). Clinical measurements
obtained at baseline and 1, 5 and 10 years after the surgical procedure were compared.
Description:
Study Population and Experimental Design The study was designed as a randomized,
prospective, split-mouth, controlled clinical trial. It was conducted in accordance with the
guidelines of the World Medical Association Declaration of Helsinki (version VI, 2002),
after approval of the study design and consent by the Faculty of Medicine, Ethical Committee
of Medical Research, Federal Fluminense University (Approval protocol CEP-HUAM/CCM 21/03).
Written informed consent was obtained from all subjects. Systemically healthy patients with
moderate to advanced chronic periodontitis referred to the Department of Periodontology,
Faculty of Dentistry, Federal Fluminense University for periodontal treatment of advanced
periodontitis were recruited for and treated in the study.
Inclusion criteria of the study were: (a) adult subjects with chronic periodontitis
presenting (b) radiographic evidence alveolar bone loss at the proximal aspect of the tooth,
(c) intrabony defect deeper than 4mm, (d) probing pocket depth >6 mm at the site, (e)
unremarkable general health according to medical history and clinical judgment, (f) no
medications taken for at least six months and no antibiotics taken for twelve months before
the beginning of the study. Subjects who have quit the habit of smoking for at least one
year before the beginning of the study were considered as non-smokers and, if the other
included criteria were met, were included in the present sample. Exclusion criteria for the
study were: (a) subjects with "early onset" or aggressive forms of periodontitis, (b)
current smokers, (c) presence of significant systemic diseases (i.e., cancer, AIDS,
diabetes), (d) clinical evidence of furcation defects, (e) presence of apical radioleucency
and (f) previous lack of cooperation with the maintenance program.
Two defects were selected from each patient, and were randomly assigned, immediately before
each surgical appointment, by computer generated random sequence allocation to one of the
two treatment modalities employed: (a) Control: open instrumentation of the root surfaces
and bone defects via flap modified papilla preservation flap; (b) Test: open instrumentation
of the root surfaces and bone defects via flap modified papilla preservation flap and
application of a rhFGF-2/HA in the intrabony defect. Treatment allocation was registered in
an allocation table sheet that was unavailable to the clinical examiner throughout the
study. Both the control and test sites were treated at the same surgical appointment and no
information on treatment allocation was provided to the patient. All surgical procedures
were performed by a single operator, which became aware of the site allocation only after
completed root planning and conditioning, and immediately before the application of the
growth factor in the test sites. A strict surgical protocol emphasizing careful hard- and
soft-tissue management, root debridement, wound stability and infection control was employed
(Santana et al 2009; Miranda et al 2013). Nonsurgical infection control was performed in the
context of cause- related periodontal therapy and consisted of oral hygiene instructions,
scaling and root planing, tooth polishing and plaque control measures performed six months
prior to regenerative surgery. Patients were re-evaluated three and six months after the
completion of the non-surgical cause-related periodontal therapy and enrolled following the
later evaluation appointment.
Clinical Recordings Clinical parameters were assessed using the cemento-enamel junction
(CEJ) or, when applicable, another defined landmark, as a fixed reference point. All
measurements were recorded using an UNC #15 periodontal probe (PCP-UNC 15, Hu-Friedy,
Chicago, IL, USA) by a blinded, trained and calibrated examiner (CMMS), unaware of the
treatment provided at baseline and one year after treatment. Measurements were recorded to
the nearest mm. Full mouth plaque score (FMPS) was recorded dichotomously as the percentage
of total surfaces (four sites per tooth) (O'Leary et al. 1972). BOP was also assessed
dichotomously at the same sites, and a full mouth bleeding score was calculated. Recession
(REC) was measured as the distance from the CEJ to the gingival margin (GM). Probing depth
(PD) was measured as the distance from the GM to the bottom of the gingival sulcus. PD and
REC were used to calculate the vertical clinical attachment level (PAL). Under local
anesthesia, transgingival probing was performed and the distance between the CEJ and the
bottom of the defect (distance CEJ-BD) was also recorded. Clinical measurements obtained at
baseline (immediately before surgery) and at twelve months are reported. After debridement
of the surgical site, the bottom of the defect (BD) was defined as the distance between
cemento-enamel junction and base of the defect. Bone crest level (BC) was measured as the
distance between the cementoenamel junction and crest of the defect and the intra-bony
defect depth (INTRA) was measured as the subtraction of BC from BD measurements (BD-BC).
Moreover, the depth of the three, two and one-wall sub-components of the bony defect were
also measured. The primary and secondary outcome variables of the present study were,
respectively, change in PAL and bone gain (change in distance CEJ-BD).
In order to ensure the reproducibility and consistency of pre- and post-intervention
measurements, examiner calibration was performed before the beginning of the study. Fourteen
sites, in seven patients, with probing depths >6 mm were evaluated by the examiner on two
separate occasions, 48h apart.
Flap Design Intracrevicular incisions were made and buccal and lingual mucoperiosteal flaps,
including at least one tooth mesial and another distal the tooth being treated, were
elevated by blunt dissection. Extreme care was taken to preserve the marginal gingiva and
inter-dental tissue to achieve better closure of the treated sites. Thus, the
defect-associated inter-dental papilla was accessed with papilla preservation flap techniques
(Takey 1985, Cortellini et al. 1995, Cortellini et al. 1999) according to indications. A
vertical releasing incision was performed at the mesial aspect of the flap whenever
necessary to obtain optimized, tensionless, access to the surgical area.
Root and bone defect debridement The bone defect was meticulously debrided with surgical
curettes and ultrasonic instruments with special effort to remove all the inflammatory
granulation tissue, but with no intention to perforate the cortical bone walls. Thorough
root planing was performed with hand (Hu-Friedy, IL, USA), rotary (Intensiv, Grancia,
Switzerland) and ultrasonic instruments (Cavitron, Dentisply, USA), to remove subgingival
plaque and calculus until all root surfaces attained a hard glassy surface. During the
instrumentation, the flaps were slightly elevated, carefully protected with periosteal
elevators, and frequently irrigated with saline.
Root conditioning and rhFGF-2 application After instrumentation, the root surfaces were
washed with saline solution to remove any remaining detached fragments from the defect and
surgical field. Then, a freshly prepared tetracycline hydrochloride paste in saline was
applied with gentle circular movements on the instrumented and dried root surfaces of both
test and control groups for three minutes. After that, the defect area was carefully rinsed
with saline. Finally, on the experimental sites, 0.2ml of a gel containing 4mg/ml rhFGF-2 in
sodium hyaluronate MW 1.3 x 106 was applied on the dried root surfaces and bone defect. The
flaps were then repositioned and tension-free primary flap closure was obtained using
internal mattress, and single interrupted sutures (5.0 Ethicon Sutures, Johnson & Johnson,
NJ, USA or Gore-tex Sutures, W.L Gore, AZ, USA).
Post-Operative Treatment The patients were prescribed systemic antibiotic therapy consisting
of 200mg of doxycycline***** the day before surgery, followed by 100 mg daily continued
until the 20th day after surgery. No surgical dressing was used. The patients were
instructed to continue their regular home hygiene care, except in the operated area, which
was cleaned by means of gentle topical applications of 0.2% chlorhexidine gluconate
(Perioxidin®, Lacer, Barcelona, Spain) in saturated cotton swabs. Patients were instructed
not to brush or floss the surgical area for 4 weeks, when mechanical plaque control was
re-instituted. The sutures were removed two weeks after surgery. Hyper-mobile teeth were
splinted either before or immediately after the surgical procedure.
Maintenance Schedule Patients were enrolled in a stringent post-operative supportive care
programme following surgery (Santana et al 2009). All patients were seen weekly during the
first three months and bi-weekly for the next three months. Thereafter, the patients were
seen once monthly for the last six-month period of the study. After 1 year, the patients
were recalled and re-instructed on proper oral hygiene. Sites were rescaled when indicated.
Radiographic assessments Radiographs were taken with a parallel, standardized, technique at
baseline (Eickholz et al. 2004). Radiographs were digitized and analysed using NIH Image
Analysis software. The anatomical landmarks for the study included cementum-enamel junction
(CEJ), alveolar crest (AC) and base of the defect (BD) (Schei et al. 1959). Radiographic
defect depth was measured along the root surface, parallel to the root axis, as the distance
between CEJ and BD.
Statistical Analyses Quantitative data were recorded as mean and standard deviations. No
data points were missing. Sample size was determined by Power analysis, assuming a standard
deviation of the difference of 0.5, which indicated that with a sample of 20 subjects, the
study would have >90% power to detect a 1-mm difference in the primary outcome measures PAL
gain and CEJ-BD reduction between the two groups. In order to verify the normality of the
data, the kurtosis and skewness curves were used. Because all data were considered to be
normal for the parameters analysed, Student's paired t-test was used for intra-group
(baseline versus 12 months) and inter-group (test versus control) comparisons. The level of
significance set at 5% was used in all statistical comparisons performed in the software
ProStat (Poly Software International, Pearl River, NY, USA) .
