Leukocyte- and Platelet-Rich Fibrin in the Surgical Treatment of Medication-related Osteonecrosis of the Jaw (PeRFOrMand)

Use of Leukocyte- and Platelet-Rich Fibrin in the Surgical Treatment of Medication-related Osteonecrosis of the Jaw: a Randomized Controlled Trial

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious side-effect of antiresorptive therapies used in the management of bone diseases, such as osteoporosis or bone metastases. A surgical management can lead to a resolution of the disease, but with perfectible results. For this purpose, the use of autologous platelet concentrates (APC) can be useful. With this study, researchers aim to demonstrate the efficacy of L-PRF (Leukocyte- and Platelet-Rich Fibrin) as an adjunct to the surgical treatment of MRONJ in terms of wound healing.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteonecrosis of the Jaw
• Intervention / Treatment: Procedure: Surgery with the use of L-PRF; Procedure: Standard surgery

Detailed Description

Resulting in bone loss, infection, pain or discomfort, the presence of MRONJ decreases the quality of life of patients. There isn't any consensus about the treatment modalities for MRONJ, nor about its main goals. Traditionally, therapeutics only aimed to control and prevent the progression of the disease, but recent studies suggest that a whole resolution can currently be expected, especially from surgical therapies. These, when indicated, are not only intended for the removal of the pathological tissue, but above all for an hermetic mucosal healing, preventing secondary infection of the underlying bone.

The L-PRF (Leukocyte- and Platelet-Rich Fibrin) is a second-generation APC, produced in a strictly autologous way, by extemporaneous centrifugation of the patient's own blood. A fibrin clot, containing leukocytes and thrombocytes, is thereby isolated and transformed into membranes by compression. Their appliance to the surgical site allows a slow release of growth factors and cytokines with a positive effect on the revascularization of the wound.

Unfortunately, scientific evidence of their efficiencies is lacking. Therefore, a protocol of randomized clinical trial is proposed, aimed at evaluating the effect of the adjunction of APC to surgical procedures on the complete mucosal healing and thus the resolution of the MRONJ.

The control treatment strategy consists of the complete removal of the necrotic bone, in bleeding margins, followed by a tension-free and hermetic closure. In the test group, suturing will be preceded by the application of L-PRF membranes under the wound.

Patients will be followed for 6 months, during which the maintain of wound closure will be monitored. An evaluation of pain, health-related quality of life and oral health-related quality of life, will also be reported, such as the occurrence of adverse events.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Franck DELANOË, MD; Phone Number: +33 5 61 77 74 76; Email: delanoe.f@chu-toulouse.fr

Study Locations

• France
  • Bordeaux, France
    • University Hospital - Centre François-Xavier Michelet
    • Contact: Mathieu BONDAZ, MD; Phone Number: +33 05 56 79 56 79; Email: mathieu.bondaz@chu-bordeaux.fr
    • Principal Investigator: Mathieu BONDAZ, MD
  • Bordeaux, France
    • University Hospital - Groupe hospitalier Pellegrin
    • Contact: Jean-Christophe FRICAIN, MD; Phone Number: +33 05 56 79 56 79; Email: jean-christophe.fricain@u-bordeaux.fr
    • Principal Investigator: Jean-Christophe FRICAIN, MD
  • Limoges, France
    • University Hospital
    • Principal Investigator: Julie USSEGLIO, MD
    • Contact: Julie USSEGLIO, MD; Phone Number: +33 05 55 05 61 20; Email: julie.usseglio@chu-limoges.fr
  • Montpellier, France
    • University Hospital Gui de CHAULIAC
    • Contact: Marie DE BOUTRAY, MD; Phone Number: +33 04 67 33 68 03; Email: m-deboutray@chu-montpellier.fr
    • Principal Investigator: Marie DE BOUTRAY, MD
  • Paris, France, 75013
    • University Hospital Pitié-Salpêtrière
    • Contact: Géraldine LESCAILLE, MD; Phone Number: +33 01 42 17 84 16
    • Principal Investigator: Géraldine LESCAILLE, MD
  • Toulouse, France, 31000
    • University Hospital
    • Contact: Franck DELANOE, MD; Phone Number: +33 05 61 77 74 76; Email: delanoe.f@chu-toulouse.fr
    • Principal Investigator: Franck DELANOE, MD
  • Toulouse, France
    • University Hospital
    • Contact: Clément CAMBRONNE, MD; Phone Number: +33 06 78 18 54 78; Email: cambronne.c@chu-toulouse.fr
    • Principal Investigator: Clément CAMBRONNE, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• MRONJ requiring surgical treatment according to AAOMS criteria (stage 2 or 3; failure of first-line treatments; sequestration of a necrotic bone block), the resection of which needs general anesthesia;
• Affiliates or beneficiaries of a social security scheme.
• Having given free and informed written consent.

Exclusion Criteria:

• Presence of a maxillo-mandibular neoplastic lesion;
• Presence of several MRONJ lesions;
• History of cervico-facial radiotherapy;
• Contraindication to general anesthesia;
• Reduced life expectancy (estimated at less than 6 months).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Patients will benefit from surgery with the use of L-PRF.	Procedure: Surgery with the use of L-PRF; The study protocol is the same as the standard surgery one but with additional use of L-PRF membranes
Other: Control group; Patients will benefit from standard surgical treatment.	Procedure: Standard surgery; The standard surgical treatment, taking place in the operating room under general anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the efficacy of the use of L-PRF during the surgical treatment of MRONJ, compared to surgical treatment alone, on complete mucosal healing.	Proportion of subjects presenting complete mucosal healing, i.e. a return to stage 0 or the "at risk" stage of the AAOMS classification.	6 months postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRONJ stage - Month 1	Evaluation and comparison between the 2 groups of the evolution of the MRONJ stage - (improvement, stability, worsening).	1 month postoperatively
MRONJ stage - Month 3	Evaluation and comparison between the 2 groups of the evolution of the MRONJ stage - (improvement, stability, worsening).	3 months postoperatively
MRONJ stage - Month 6	Evaluation and comparison between the 2 groups of the evolution of the MRONJ stage - (improvement, stability, worsening).	6 months postoperatively
the postoperative pain - Month 1	Pain will be subjectively evaluated by the patients using a Numerical Scale, according to a score from 0 (absence of pain) to 10 (maximum pain imaginable).	1 month postoperatively
the postoperative pain - Month 3	Pain will be subjectively evaluated by the patients using a Numerical Scale, according to a score from 0 (absence of pain) to 10 (maximum pain imaginable).	3 months postoperatively
the postoperative pain - Month 6	Pain will be subjectively evaluated by the patients using a Numerical Scale, according to a score from 0 (absence of pain) to 10 (maximum pain imaginable).	6 months postoperatively
health-related quality of life - Month 1 - World Health Organization Quality of Life WHOQOL-BREF	Overall quality of life will be assessed by the WHOQOL-BREF questionnaire	1 month postoperatively
health-related quality of life - Month 1 - OHIP-14	oral health-related quality of life will be assessed via the OHIP-14 questionnaire.	1 month postoperatively
health-related quality of life - Month 3 WHOQOL-BREF	Overall quality of life will be assessed by the WHOQOL-BREF questionnaire and oral health-related quality of life will be assessed via the OHIP-14 questionnaire.	3 months postoperatively
health-related quality of life - Month 3 Oral health-related quality OHIP-14	Oral Health Impact Profile of life will be assessed via the Oral Health Impact Profile OHIP-14 questionnaire.	3 months postoperatively
health-related quality of life - Month 6 WHOQOL-BREF	Overall quality of life will be assessed by the WHOQOL-BREF questionnaire	6 months postoperatively
health-related quality of life - Month 6 - OHIP-14	Oral health-related quality of life will be assessed via the OHIP-14 questionnaire.	6 months postoperatively

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Claire VILLEPINTE, MD, University Hospital, Toulouse

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: May 16, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: surgical; PRF; therapeutics; Platelet-Rich Fibrin; autologous platelet concentrates
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Musculoskeletal Diseases; Bone Diseases; Osteonecrosis
• Other Study ID Numbers: RC31/21/0165

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