Use of a Bone Substitute Material in the Surgical Therapy of Furcation Defects

The Use of a Bone Substitute Material in the Surgical Therapy of Furcation Defects - a Multi-center Randomized Controlled Trial

The aim of this randomized clinical trial is to evaluate the potential benefit of the use of a bone substitute material in the treatment of furcation degree II-involved molars. The main question it aims to answer is: What is the benefit of the adjunctive use of a bone substitute material in the surgical treatment of furcation degree II-involved molars when compared to open-flap debridement alone?

200 patients with ≥1 molar presenting with a furcation defect degree II will be included and randomized to either control (open-flap debridement) or test treatment (open-flap debridement + bone substitute material). The primary outcome of the study is furcation closure defined as absence of clinically detectable furcation involvement degree >I. Secondary outcomes include changes in bleeding on probing, probing depth, vertical and horizontal attachment levels, soft tissue level, marginal bone level, need for surgical retreatment, tooth loss, patient-reported outcomes and adverse events. A composite outcome based on furcation closure (degree ≤I) in combination with shallow probing depth (≤5 mm) and absence of bleeding on probing will also be evaluated.

Study Overview

• Status: Not yet recruiting
• Conditions: Periodontitis; Furcation Defects
• Intervention / Treatment: Procedure: Access flap & surgical debridement; Procedure: Application of bone substitute material (BioOss Collagen)

Detailed Description

The study will be conducted as a randomized controlled trial with a 12-month follow-up at multiple clinical centers throughout Europe. All study-related procedures are to be performed by specialists in periodontics or clinicians in specialist training. 200 patients with ≥1 molar with a furcation defect degree II (pre-surgical assessment) will be enrolled in the study. Following the primary evaluation at 12 months, study participants will be followed up to 10 years.

Preparatory phase Prior to surgery, patients will be provided with tailored non-surgical periodontal therapy including instructions in self-performed plaque control measures and supra- and subgingival instrumentation. The preparatory phase is concluded by an examination 8-16 weeks after completion of the non-surgical instrumentation.

Surgical intervention Following local anesthesia, full thickness flaps at target molars will be elevated and inflamed tissues are removed. Root surfaces are then instrumented using an ultra-sonic device with a standardized tip under irrigation with saline. Upon completion of root instrumentation, group allocation is revealed and a bone substitute material will be placed in the furcation defect to the level of the outer contour of the roots in the test group. Flaps will be repositioned and sutured to cover the entirety of the furcation area aiming for primary closure. The same procedure, omitting the placement of the bone substitute material, will be performed in the control group.

Patients will refrain from mechanical self-performed plaque control measures in the surgical area for 4 weeks post-surgery. During this period, daily rinsing with a 0.2% solution of chlorhexidine digluconate is prescribed.

Follow-up Sutures will be removed after two weeks and patient-reported experience (PRE) is scored. Patients will then be seen for oral hygiene instructions at 4 weeks and for supportive periodontal therapy at 3, 6, 9 and 12 months. Treatment and patient-reported outcomes (PROs) will be evaluated at 6 and 12 months. Additional examinations are carried out at 3, 5, 7 and 10 years.

Clinical assessments Clinical examinations at baseline and during follow-up will be performed by calibrated and blinded examiners. The following parameters will be recorded at all included teeth: degree of furcation, horizontal and vertical attachment levels. Bleeding on probing and plaque (yes/no), and probing pocket depth (mm), will be scored. Soft tissue levels will be assessed relative to the cemento-enamel junction.

During the surgical intervention, dimensions of the furcation defect will be noted. Adverse events will be noted

Radiographic assessments Standard intra-oral radiographs will be obtained at baseline, at 12 months and at years 3, 5 and 10. Assessments with regard to bone level changes and interradicular bone fill will be performed by an examiner blinded to group allocation.

Biomarkers In a nested approach, two centers (Gothenburg & London) will perform evaluations of inflammatory markers during healing. Prior to the surgical intervention and at 2 weeks, 6 months and 12 months, samples of gingival crevicular fluid (GCF) will be obtained. GCF will be collected at the target site as well as the contra-lateral molar (or alternative tooth if missing) utilizing PerioPaper strips. Inflammatory markers (eg IL-1, IL-6) will be evaluated through ELISA.

Questionnaire Patients will be asked to complete an assisted questionnaire at baseline, as well as at 6 and 12 months (PROs). Questions addressing patient satisfaction and potential discomfort after treatment are answered by means of a visual analogue scale (10 cm). Patient-reported experiences (PREs) will be scored at the 2-week control visit following the surgical intervention.

Enrolment, randomization, group allocation and blinding Patients meeting the inclusion criteria following completion of the preparatory phase will be invited on a consecutive basis. Upon signed consent, participants are enrolled and assigned a unique identification number, by which patients are randomly allocated to one of two study arms. Randomization (ratio 1:1) is performed by computer-generated lists with permuted blocks of eight and stratified for smoking. Allocation is concealed by the use of opaque envelopes not opened until completion of the surgical debridement. Examiners at baseline and during follow-up will be blinded to group allocation.

Data analysis Categorical and continuous variables originating from the clinical, radiographic and biomarker assessments will be evaluated by regression analyses adjusted for group allocation, time point (repeated measurements: baseline, 6 months, 1 year, etc.), smoking and tooth/furcation location (site; 1st vs 2nd molar; mandible vs maxilla). An intention-to-treat approach will be followed. It is assumed that drop-out will occur at random. Hence, latest available data points will be moved forward. A potential center effect will be evaluated. PROs are expected to be not-normally distributed and will be assessed through non-parametric methods.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jan Derks, PhD; Phone Number: +46766183124‬; Email: jan.derks@odontologi.gu.se
• Study Contact Backup: Name: Kostas Bougas, PhD; Phone Number: +46766181208; Email: kostas.bougas@gu.se

Study Locations

• Sweden
  • Göteborg, Sweden, 40530
    • Department of Periodontology, Institute of Odontology
    • Contact: Jan Derks, PhD; Phone Number: 0046 76 618 3124; Email: jan.derks@odontologi.gu.se
    • Principal Investigator: Jan Derks, PhD
    • Sub-Investigator: Karolina Karlsson, PhD
    • Sub-Investigator: Kostas Bougas, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients should present with at least one surgically accessible molar (in tooth position 6 or 7) diagnosed with a single furcation defect degree II (at any aspect).

Following initial periodontal therapy, teeth to be included should present with one site with furcation defect degree II in combination with:

• Bleeding on probing
• Probing pocket depth of ≥6 mm
• Soft tissue coverage of the furcation entrance Patients should present with a full mouth plaque score ≤25%.

Exclusion Criteria:

• Multiple deep furcation defects (degree II - III) at the same tooth
• Vertical attachment loss >50% at aspects not facing the furcation defect
• Defects presenting with apico-marginal communication
• Intake of systemic antibiotics within 6 months
• Systemic conditions/medication impeding surgical intervention (e.g. uncontrolled diabetes, immunosuppressive medication)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Access flap + bone substitute; Furcation defect will be treated by access flap debridement followed by application of a bone substitute material.	Procedure: Access flap & surgical debridement; Following surgical exposure, roots are carefully debrided.; Procedure: Application of bone substitute material (BioOss Collagen); Following surgical debridement, the bone substitute material is applied to the furcation defect.
Active Comparator: Access flap; Furcation defect will be treated by access flap debridement alone.	Procedure: Access flap & surgical debridement; Following surgical exposure, roots are carefully debrided.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients/teeth displaying furcation closure.	Furcation closure defined as absence of clinically detectable furcation involvement degree >I.	6 months.
Proportion of patients/teeth displaying furcation closure.	Furcation closure defined as absence of clinically detectable furcation involvement degree >I.	12 months.
Proportion of patients/teeth displaying furcation closure.	Furcation closure defined as absence of clinically detectable furcation involvement degree >I.	3 years.
Proportion of patients/teeth displaying furcation closure.	Furcation closure defined as absence of clinically detectable furcation involvement degree >I.	5 years.
Proportion of patients/teeth displaying furcation closure.	Furcation closure defined as absence of clinically detectable furcation involvement degree >I.	7 years.
Proportion of patients/teeth displaying furcation closure.	Furcation closure defined as absence of clinically detectable furcation involvement degree >I.	10 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in probing pocket depth.	Reductions in PPD relative to baseline.	6 months.
Changes in probing pocket depth.	Reductions in PPD relative to baseline.	12 months.
Changes in probing pocket depth.	Reductions in PPD relative to baseline.	3 years.
Changes in probing pocket depth.	Reductions in PPD relative to baseline.	5 years.
Changes in probing pocket depth.	Reductions in PPD relative to baseline.	7 years.
Changes in probing pocket depth.	Reductions in PPD relative to baseline.	10 years.
Changes in bleeding on probing.	Reductions in BOP relative to baseline.	6 months.
Changes in bleeding on probing.	Reductions in BOP relative to baseline.	12 months.
Changes in bleeding on probing.	Reductions in BOP relative to baseline.	3 years.
Changes in bleeding on probing.	Reductions in BOP relative to baseline.	5 years.
Changes in bleeding on probing.	Reductions in BOP relative to baseline.	7 years.
Changes in bleeding on probing.	Reductions in BOP relative to baseline.	10 years.
Changes in vertical and horizontal clinical attachment level.	Changes in clinical attachment levels relative to baseline.	6 months.
Changes in vertical and horizontal clinical attachment level.	Changes in clinical attachment levels relative to baseline.	12 months.
Changes in vertical and horizontal clinical attachment level.	Changes in clinical attachment levels relative to baseline.	3 years.
Changes in vertical and horizontal clinical attachment level.	Changes in clinical attachment levels relative to baseline.	5 years.
Changes in vertical and horizontal clinical attachment level.	Changes in clinical attachment levels relative to baseline.	7 years.
Changes in vertical and horizontal clinical attachment level.	Changes in clinical attachment levels relative to baseline.	10 years.
Changes in marginal soft tissue levels.	Changes in marginal soft tissue levels relative to baseline.	6 months.
Changes in marginal soft tissue levels.	Changes in marginal soft tissue levels relative to baseline.	12 months.
Changes in marginal soft tissue levels.	Changes in marginal soft tissue levels relative to baseline.	3 years.
Changes in marginal soft tissue levels.	Changes in marginal soft tissue levels relative to baseline.	5 years.
Changes in marginal soft tissue levels.	Changes in marginal soft tissue levels relative to baseline.	7 years.
Changes in marginal soft tissue levels.	Changes in marginal soft tissue levels relative to baseline.	10 years.
Changes in radiographic bone levels.	Changes in radiographic bone levels relative to baseline.	12 months.
Changes in radiographic bone levels.	Changes in radiographic bone levels relative to baseline.	3 years.
Changes in radiographic bone levels.	Changes in radiographic bone levels relative to baseline.	5 years.
Changes in radiographic bone levels.	Changes in radiographic bone levels relative to baseline.	10 years.
Patient satisfaction assessed by visual analogue scale.	Patient satisfaction as assessed on a 100 mm VAS.	6 months.
Patient satisfaction assessed by visual analogue scale.	Patient satisfaction as assessed on a 100 mm VAS.	12 months.
Patient discomfort as expressed on a visual analogue scale.	Patient discomfort following surgical therapy as expressed on a 100 mm VAS.	2 weeks.
Patient discomfort as expressed on a visual analogue scale.	Patient discomfort following surgical therapy as expressed on a 100 mm VAS.	6 months.
Esthetic appreciation as expressed on a visual analogue scale.	Esthetic appreciation as expressed on a 100 mm VAS.	6 months.
Esthetic appreciation as expressed on a visual analogue scale.	Esthetic appreciation as expressed on a 100 mm VAS.	12 months.
Rate of adverse events.	Impaired healing following surgical intervention.	2 weeks.
Rate of adverse events.	Impaired healing following surgical intervention.	12 months.
Tooth loss.	Event of tooth loss during follow-up.	12 months.
Tooth loss.	Event of tooth loss during follow-up.	3 years.
Tooth loss.	Event of tooth loss during follow-up.	5 years.
Tooth loss.	Event of tooth loss during follow-up.	7 years.
Tooth loss.	Event of tooth loss during follow-up.	10 years.
Need for retreatment.	Need for surgical retreatment of included site.	12 months.
Need for retreatment.	Need for surgical retreatment of included site.	3 years.
Need for retreatment.	Need for surgical retreatment of included site.	5 years.
Need for retreatment.	Need for surgical retreatment of included site.	7 years.
Need for retreatment.	Need for surgical retreatment of included site.	10 years.
Change of inflammatory markers.	Change of inflammatory markers measured in gingival crevicular fluid.	2 weeks.
Change of inflammatory markers.	Change of inflammatory markers measured in gingival crevicular fluid.	6 weeks.

Collaborators and Investigators

• Sponsor: Göteborg University
• Collaborators: King's College London; Charite University, Berlin, Germany; Geistlich Pharma AG; Queen Mary University of London; Vastra Gotaland Region; Johann Wolfgang Goethe University Hospital
• Investigators: Study Director: Karolina Karlsson, PhD, Göteborg University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2036

Study Registration Dates

• First Submitted: February 13, 2024
• First Submitted That Met QC Criteria: February 13, 2024
• First Posted (Estimated): February 21, 2024

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Surgical therapy; Reconstructive
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Periodontitis; Furcation Defects
• Other Study ID Numbers: 2023-00383-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No