Clinical trial NCT05572242: Leukocyte-platelet Rich Fibrin for Alveolar Ridge Preservation
Official title: Autologous Leukocyte-platelet Rich Fibrin (L-PRF) Versus a Xenogeneic Bone Substitute Combined With a Collagen Matrix for Alveolar Ridge Preservation. A Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Alveolar Ridge Enlargement
Keywords: tooth extraction
socket graft
L-PRF
xenogenic bone
dental implant
Lead sponsor: Universidad de los Andes, Chile
Sponsor class: OTHER
Collaborators: name: Geistlich Pharma AG
name: BioHorizons, Inc.
First posted: 2022-10-07
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a non-inferiority clinical controlled trial of parallel groups
Primary purpose: TREATMENT

Brief summary: After tooth extraction, there is a subsequent bone loss as a part of the natural healing of the tissue. Up to 50% of bone loss occurs during the first three months after extraction, jeopardizing a possible implant treatment. Alveolar ridge preservation techniques reduce bone loss, allowing a future implant treatment. Different bone filling materials have been used with good clinical results. The second-generation platelet concentrates (L-PRF) have recently been shown to induce bone regeneration when filling the socket after extraction, with significant biological and economic advantages. The hypothesis of this study is to test whether or not the use of L-PRF in alveolar ridge preservation results in a non-inferior horizontal radiographic change compared with the combination of a xenogeneic bone substitute with a collagen matrix.

Detailed description: This study is a non inferiority clinical controlled trial of parallel groups. Study Intervention and Indication

After single premolar extractions in the maxilla or mandible area, patients will be randomly allocated to either one of the two treatment modalities:

* Alveolar ridge preservation using L-PRF (test)
* Alveolar ridge preservation using xenogeneic bone covered with a collagen matrix (control)

Study objectives Primary Objective The present study aims to test whether or not the use of L-PRF in alveolar ridge preservation results in non-inferior horizontal ridge width changes measured at - 1 mm below the most coronal aspect of the alveolar crest compared to the combination of a xenogeneic bone substitute material with a collagen matrix, 4 months after tooth extraction.

Clinical procedures

Extraction surgery

Partially edentulous patients in need of a single-tooth extraction in the premolar region (maxilla or mandible), with two neighboring natural teeth, will be included. All surgical procedures will be performed under local anesthesia. After disinfection of the surgical site with 0.2% chlorhexidine solution (PerioAid® Treatment, Barcelona, Spain), local anesthetics (Lidocaine HCl 2% with epinephrine 1:100,000; XXX) will be administered by infiltration at the respective buccal and lingual sites at maxilla or inferior alveolar nerve block technique on the mandible. The tooth will be luxated first with straight and angled elevators and then carefully extracted with forceps without raising a flap. After that, patients will be randomly assigned to either one of the two treatment modalities:

* Alveolar ridge preservation with leukocyte-platelet rich fibrin (L-PRF) (test)
* Alveolar ridge preservation using xenogeneic bone covered with a collagen matrix (DBBM+CM) (control)

Clinical procedures A venepuncture will be performed before any surgery (irrespective of the later randomization). Six plastic sterile 9 mL tubes without anticoagulant will be drawn with venous blood from the median basilica vein, median cubital vein, or median cephalic vein. Preparation of the L-PRF clots and membranes will be performed as previously described. In brief, within 60 seconds after the blood draws, the tubes will be centrifuged at 408 g RCF for 12 min using a tabletop centrifuge (IntraSpinTM, IntraLock®, Florida, USA). Following centrifugation, L-PRF clots will be removed from the tube, separated from the remaining red thrombus at the base with tweezers, and gently compressed into membranes using a metal rack and a metal plate.

Extraction surgery

Partially edentulous patients needing a single-tooth extraction in the premolar region (maxilla or mandible), with two neighboring natural teeth, will be included in the study. All surgical procedures will be performed under local anesthesia. After disinfection of the surgical site with 0.2% chlorhexidine solution (PerioAid® Treatment, Barcelona, Spain), local anesthetics (Lidocaine HCl 2% with epinephrine 1:100,000; XXX) will be administered by infiltration at the respective buccal and lingual sites at maxilla or inferior alveolar nerve block technique on the mandible. The tooth will be luxated first with straight and angled elevators and then carefully extracted with forceps without raising a flap. After that, patients will be randomly assigned to either one of the two treatment modalities:

* Alveolar ridge preservation with leukocyte-platelet rich fibrin (L-PRF) (test)
* Alveolar ridge preservation using xenogeneic bone covered with a collagen matrix (DBBM+CM) (control)

In group L-PRF group, 2-5 PRF clots, depending on the size of the socket, will be inserted and compressed with a large plunger until they reach the alveolar crest as previously described (Temmerman et al., 2016). The site will thereafter be covered with 2-3 L-PRF membranes. Then, crossed horizontal mattress suture will be placed, followed by single interrupted sutures for better stabilization (Vicryl 4.0 EthiconTM, Johnsson \& Johnsson, New Jersey, New York, USA). No efforts will be undertaken to obtain primary wound closure. The grafted socket will be left to heal for 4 months.

In group DBBM+CM, the socket will be grafted with xenogeneic bone substitute material (up to the palatal/lingual bone crest) and covered with a collagen matrix. Single interrupted sutures (Vicryl 4.0 EthiconTM, Johnsson \& Johnsson, New Jersey, New York, USA) will be placed to stabilize the collagen matrix. Sutures will be removed within 7-10 days. The grafted socket will then be left to heal for 4 months.

The xenogenic material DBBM will be Bio-Oss Collagen®, and collagen matrix Bio-Gide® both delivered as the Combi-Kit Collagen (Geistlich Pharma AG - Switzerland).

Immediately after surgery, despite the treatment group, the patient will be scanned using a CBCT (cone beam computed tomography)

Implant surgery

At 4 months, patients from both groups will be recalled for implant placement. Before the surgery, a CBCT and an impression will be taken. Moreover, clinical data will be recorded. Upon local anesthesia, a full flap will be raised, and a biopsy will be taken in the center of the implant site using a trephine drill (inner diameter 2mm). Thereafter, the implant will be placed according to the manufacturer's recommendation. A submerged healing protocol will be allowed. Final reconstructions will be inserted 4 months later.

* Type of implants: Biohorizons 3.8 \* 10.5 mm as a standard implant, inserted at bone level.
* Healing mode: Submerged
* No provisional reconstruction
* Type of final reconstruction: Cad-cam screw-retained and axis screw, depending on the case.

Follow-up examinations Follow-up examinations will be performed at baseline 2 (10 days after crown insertion), 6 months, and 1 year after final restoration.

Eligibility criteria: Inclusion Criteria:

1. Periodontally healthy individuals with at least 18 years of age
2. Good oral hygiene (BOP \& Pl ≤ 20%)
3. Patients with a single failing premolar in the maxilla and mandible.
4. With or without buccal plate after tooth extraction (similar cases in both groups)
5. Surrounded by a mesial and distal natural tooth
6. Capability to comply with the study procedures
7. Informed Consent as documented by signature

Exclusion Criteria:

1. Pregnant or lactating women
2. Known or suspected non-compliance, drug or alcohol abuse
3. Smokers (\>10 cigarettes/day)
4. Systemic or local conditions presenting a contraindication to implant treatment
5. Currently taking drugs that influence bone metabolism
6. Use of bisphosphonates in the last 4 years
7. History of malignancy, radiotherapy or chemotherapy for malignancy in the past 5 years

Primary outcomes:
measure: Bone socket horizontal and vertical changes evaluated using cbct ((cone beam computed tomography)
timeFrame: first cbct immediately after socket preservation surgery, second cbct 4 months after surgery, 12 months after the final restoration of the implant.
Secondary outcomes:
measure: Mucosal height
timeFrame: 4 months after implant insertion, at the final restoration delivery
measure: Peri-implant Keratinized Mucosa
timeFrame: 10 days, 6, and 12 months after final restoration
measure: Bleeding on probing
timeFrame: 10 days, 6, and 12 months after final restoration
measure: Probing depth
timeFrame: 10 days, 6, and 12 months after final restoration
measure: Profilometric Changes
timeFrame: at baseline (socket preservation), 4 months (implant insertion), 10 days and 12 months after final restoration delivery
measure: Phenotype
timeFrame: 10 days, 6 and 12 months after final restoration
measure: Pink esthetic score (PES)
timeFrame: 10 days, 6, and 12 months after final restoration
measure: White esthetic score (WES)
timeFrame: 10 days, 6, and 12 months after final restoration
measure: Visual analog scale for pain assessment (VAS)
timeFrame: Pain perceived, 24 hrs after socket preservation and implant insertion (4 months).
measure: Oral Health Impact Profile (OHIP-14)
timeFrame: at baseline, 6 and 12 months after final restoration
measure: Radiographic evaluation
timeFrame: 10 days, 6, and 12 months after final restoration
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Centro de Salud, Universidad de los Andes
state: Region Metropolitana
Study officials:
affiliation: Professor
name: Antonio Sanz, DDS
role: PRINCIPAL_INVESTIGATOR
References: