Clinical trial NCT05662709: Leukocyte and Platelet-rich Fibrin (L-PRF) Effects on Alveolar Ridge Preservation. A Randomized Controlled Clinical Trial.
Official title: Leukocyte and Platelet-rich Fibrin (L-PRF) Effects on Alveolar Ridge Preservation. A Randomized Controlled Clinical Trial With One Year Follow up
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Alveolar Ridge Preservation
Dental Implants
Keywords: platelet-rich fibrin
bone regeneration
alveolar ridge preservation
tooth extraction
Lead sponsor: Universidad Complutense de Madrid
Sponsor class: OTHER
First posted: 2022-12-22
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Controlled clinical trial, 2 groups of patients undergoing tooth extraction, allocated to:

* Test group: alveolar ridge preservation with L-PRF
* Control group: spontaneous healing of the socket
Primary purpose: TREATMENT

Brief summary: The goal of this clínical trial is to compare in patients needing extraction of anterior teeth the effects of leukocyte-and platelet-rich fibrin (L-PRF) for alveolar ridge preservation versus spontaneous healing. The main questions it aims to answer are:

* Does L-PRF use as alveolar ridge preservation material diminish volumetric changes in the alveolar ridge produced after tooth extraction and further bone regeneration needs?
* Does it have any advantage for wound healing and patient-related outcomes? Participants will undergo
* Tooth extraction
* Alveolar ridge preservation/ spontaneous healing
* Implant placement

Researchers will compare alveolar ridge preservation with L-PRF with spontaneous healing to see if there is an effect on reducing ridge dimensional changes happening after tooth extraction.

Detailed description: -Objectives

The main objective is to determine if L-PRF use as alveolar ridge preservation material diminishes volumetric changes in the alveolar ridge produced after tooth extraction and needs of bone regeneration previous or simultaneous to implant placement compared to spontaneous healing.

Secondary objectives:

To determine if there are differences in wound healing after the use of L-PRF compared to spontaneous healing.

To investigate if there are differences in Patient Reported Outcome measures after the use of L-PRF compared to spontaneous healing.

To analyse the histologic differences in quality of bone after the use of L-PRF compared to spontaneous healing.

-Material and Methods

Randomized clinical trial developed in an academic onset, parallel groups, single-blinded with one year follow up after implant loading.

Ethical Aspects:

This investigation will be based on compliance with the principles of the Declaration of Helsinki. The ethics committee of Hospital Clínico San Carlos will be in charge of evaluating and approving this protocol. All patients will be fully informed before their inclusion in the study by means of informed consent.

Treatment:

All the participants will be treated by postgraduate students at the Master of Periodontology and Implant dentistry from the Complutense University of Madrid.

Twenty-eight patients in need of extraction will be included in the study. In the baseline visit local anesthesia will be administered and tooth extraction will be performed in the least traumatic way possible. The group will be allocated according to a computer-generated randomization list and given in a sealed envelope. For the test group (L-PRF) venipuncture (median basilica vein, median cubital vein, median cephalic vein) will be performed by a nurse and blood will be drawn into 8 sterile plastic 10 ml tubes without anticoagulant (Vacutainers: IntraSpin™, Intra-lock,USA). L-PRF plugs and membranes will be prepared as described by Choukroun et al 2001. Tubes will be centrifuged for 12 minutes at 2700 rpm using a table centrifuge (IntraSpin™, IntraLock, USA). After centrifugation, clots will be removed from the tubes, separated from red element phase at the base with pliers and placed in a metal tray (Xpression™ Box). Four to five of them will be packed in a cylinder to obtain plugs, and four will be squeezed between the tray and a glass plate to obtain L-PRF membranes. In sockets of the L-PRF group, 2-5 plugs, depending on the size of the socket will be inserted and compressed and membranes will be adapted on top and inserted in vestibular and lingual envelope flaps previously prepared. A crossed horizontal mattress suture (Polyamide 5.0, Supramid™, SMI AG, Steinerberg, Belgium) will be placed on top. In the control group, after extraction, just the suture will be performed to stabilize the coagulum. Patients will be prescribed ibuprofen (600mg t.i.d) or paracetamol (1g t.i.d) and chlorhexidine 0.12% + 0.05% CPC mouth rinse (PerioAid® Tratamiento, Dentaid, Barcelona, Spain) for one week.

Follow up visits:

After extraction, a cone-beam computed tomography (CBCT) scan (i-CAT Classic, Imaging Sciences International, Hatfield, Pennsylvania) and a digital impression (Medit i500 ™, Medit, Seoul, Korea) to obtain a stereolithographic model of the area will be taken.

Sutures will be removed at 7days. Patients will attend follow-up visits at 4 weeks and 4 months to monitor wound healing. Patient reported outcome measures (PROM's) will be registered at 1 and 4 weeks.

Diagnostic for implant placement:

Four months after tooth extraction, the new CBCT will be assessed to see bone availability for implant placement. In this visit a new digital impression will be taken to assess dimensional changes in bone and soft tissue with an image analysis software (SMOP®, Swissmeda, Switzerland).

Implant surgery will be scheduled, it will be determined if bone regeneration is necessary before or simultaneously to implant placement. At the time of implant placement, a biopsy will be taken for histologic analysis with a trephine bur of 2.5mm diameter (Komet, USA) with the aim to obtain a sample of healed bone tissue and perform histologic analysis. After osteotomy, an implant Gold \& Blue (Intralock, USA) will be inserted. If there is no need of bone regeneration, healing abutments will be placed; if there is need of simultaneous bone regeneration the width and height of the defect will be registered and a bone substitute NanoBone®(Intra-lock Iberia, Madrid Spain) and a resorbable collagen membrane (Bio-Gide; Geistlich, Switzerland will be placed, with a submerged healing protocol. Four months late, second stage surgery will be performed. If implant cannot be properly stabilized, a guided bone regeneration will be performed with the same materials and implants will be placed after six months.

After implant placement, a periapical x-ray will be performed, and sutures will be removed after one week.

Implant restoration:

After a healing period of 10 weeks after implant placement (between 4-6 months if bone regeneration has been required), impressions will be taken to make the provisional or final prosthesis, STLs models for ridge changes assessment and implant related variables will be registered.

The day of implant loading, a new standardized periapical x-ray will be taken with a personalized bite block. Peri-implant health related variables will be assessed, and esthetic outcomes will be registered. This will be the baseline visit for the follow up analysis of the implants placed.

Implants follow up:

The implants will be assessed at 6 and 12 months after loading the final prosthesis. In these visits, the same clinical variables related to peri-implant health and aesthetics will be recorded as in the baseline visit (definitive load). Additionally, at 12 months a periapical X-ray will be performed, a digital impression of the treated area will be taken and a satisfaction questionnaire will be given to the patient.

-Sample size calculation

The sample size calculation was based on detecting a mean difference in reduction of the HRW of 2,3mm with an estimated standard deviation (SD) of 1.1 between groups (Thalmair et al., 2013). To detect statistically significant differences (α=0.05) with a 90% power, a minimum of 11 subjects per group are needed, which including an expected 20% drop-out rate, it resuls in a final sample of 14 participants per group.

-Data analysis

Data will be analyzed to compare both treatment modalities. The normality of the distribution will be evaluated using the Kolmogorov-Smirnov test. Depending on the distribution of the data, parametric or non-parametric tests will be used. Quantitative variables will be assessed by means of student´s t test or Mann Whitney´s U test.

Qualitative variables will be expressed through distribution frequencies and will be compared with chi-square tests.

The clinical significance level is set at p\<0.05.

Eligibility criteria: Inclusion Criteria:

* Systemically healthy patients ≥18 years old
* Need for extraction of a tooth in the anterior area (position of second premolar to second premolar in maxilla or mandible) that needs to be replaced by an implant-supported restoration
* Presence of natural teeth mesially and distally of tooth to be extracted, periodontally healthy (probing depths \<5 mm without bleeding on probing).

Exclusion Criteria:

* Systemic conditions affecting bone or soft tissue healing
* Smokers of more than 10 cigarettes a day or equivalent to cigarettes
* Breastfeeding or pregnant women
* Patients without availability to attend follow-up visits or patients rejecting to sign the informed consent

Primary outcomes:
measure: Radiographic linear changes in horizontal width of the alveolar ridge
timeFrame: From tooth extraction (Baseline) to four months healing (4m)
Secondary outcomes:
measure: Radiographic linear changes height of the alveolar ridge
timeFrame: From tooth extraction (Baseline) to four months healing (4m)
measure: Changes in ridge contour
timeFrame: From tooth extraction (Baseline) to four months healing (4m)
measure: Volumetric changes
timeFrame: From tooth extraction (Baseline) to four months healing (4m)
measure: Patient reported outcome measures
timeFrame: At one week, one month and four months visit.
measure: Bone regeneration needs
timeFrame: 4 months after tooth extraction
measure: Percentage of mineralized bone
timeFrame: 4 months after tooth extraction, during the implant placement surgery.
Other outcomes:
measure: Peri implant probing depth
timeFrame: At implant placement, 6 months and 12 months after loading
measure: Peri-implant Plaque index
timeFrame: At implant placement, 6 months and 12 months after loading
measure: Bleeding on probing
timeFrame: At implant placement, 6 months and 12 months after loading
measure: Radiographic changes in bone levels
timeFrame: At implant placement, 6 months and 12 months after loading
measure: Clinical crown dimension
timeFrame: At implant loading, 6 months and 12 months follow up
measure: Pink Esthetic Score
timeFrame: At implant loading, 6 months and 12 months follow up
measure: Changes in ridge contour after loading
timeFrame: 12 months after implant loading
Locations:
city: Madrid
country: Spain
facility: Complutense University of Madrid
Study officials:
References:
citation: Choukroun, J., Adda, F., Schoeffler, C., & Vervelle, A. (2001). The opportunity in perio-implantology: The PRF. Implantodontie, 42, 55-62.
citation: Dohan Ehrenfest DM, de Peppo GM, Doglioli P, Sammartino G. Slow release of growth factors and thrombospondin-1 in Choukroun's platelet-rich fibrin (PRF): a gold standard to achieve for all surgical platelet concentrates technologies. Growth Factors. 2009 Feb;27(1):63-9. doi: 10.1080/08977190802636713.
citation: Tan WL, Wong TL, Wong MC, Lang NP. A systematic review of post-extractional alveolar hard and soft tissue dimensional changes in humans. Clin Oral Implants Res. 2012 Feb;23 Suppl 5:1-21. doi: 10.1111/j.1600-0501.2011.02375.x.
citation: Barone A, Aldini NN, Fini M, Giardino R, Calvo Guirado JL, Covani U. Xenograft versus extraction alone for ridge preservation after tooth removal: a clinical and histomorphometric study. J Periodontol. 2008 Aug;79(8):1370-7. doi: 10.1902/jop.2008.070628.
citation: Schropp L, Wenzel A, Kostopoulos L, Karring T. Bone healing and soft tissue contour changes following single-tooth extraction: a clinical and radiographic 12-month prospective study. Int J Periodontics Restorative Dent. 2003 Aug;23(4):313-23.
citation: Sanz-Martin I, Permuy M, Vignoletti F, Nunez J, Munoz F, Sanz M. A novel methodological approach using superimposed Micro-CT and STL images to analyze hard and soft tissue volume in immediate and delayed implants with different cervical designs. Clin Oral Implants Res. 2018 Oct;29(10):986-995. doi: 10.1111/clr.13365. Epub 2018 Sep 23.
citation: Vignoletti F, Matesanz P, Rodrigo D, Figuero E, Martin C, Sanz M. Surgical protocols for ridge preservation after tooth extraction. A systematic review. Clin Oral Implants Res. 2012 Feb;23 Suppl 5:22-38. doi: 10.1111/j.1600-0501.2011.02331.x.
citation: Furhauser R, Florescu D, Benesch T, Haas R, Mailath G, Watzek G. Evaluation of soft tissue around single-tooth implant crowns: the pink esthetic score. Clin Oral Implants Res. 2005 Dec;16(6):639-44. doi: 10.1111/j.1600-0501.2005.01193.x.
citation: Ortiz-Vigon A, Suarez I, Martinez-Villa S, Sanz-Martin I, Bollain J, Sanz M. Safety and performance of a novel collagenated xenogeneic bone block for lateral alveolar crest augmentation for staged implant placement. Clin Oral Implants Res. 2018 Jan;29(1):36-45. doi: 10.1111/clr.13036. Epub 2017 Jul 14.
citation: Anwandter A, Bohmann S, Nally M, Castro AB, Quirynen M, Pinto N. Dimensional changes of the post extraction alveolar ridge, preserved with Leukocyte- and Platelet Rich Fibrin: A clinical pilot study. J Dent. 2016 Sep;52:23-9. doi: 10.1016/j.jdent.2016.06.005. Epub 2016 Jun 20.
citation: Temmerman A, Vandessel J, Castro A, Jacobs R, Teughels W, Pinto N, Quirynen M. The use of leucocyte and platelet-rich fibrin in socket management and ridge preservation: a split-mouth, randomized, controlled clinical trial. J Clin Periodontol. 2016 Nov;43(11):990-999. doi: 10.1111/jcpe.12612. Epub 2016 Sep 21.
citation: Thalmair T, Fickl S, Schneider D, Hinze M, Wachtel H. Dimensional alterations of extraction sites after different alveolar ridge preservation techniques - a volumetric study. J Clin Periodontol. 2013 Jul;40(7):721-7. doi: 10.1111/jcpe.12111. Epub 2013 May 5.
citation: Suttapreyasri S, Leepong N. Influence of platelet-rich fibrin on alveolar ridge preservation. J Craniofac Surg. 2013 Jul;24(4):1088-94. doi: 10.1097/SCS.0b013e31828b6dc3.