Best Treatment Choice for Osteonecrosis of the Jaw (BETCON)

Tim Van den Wyngaert

Status and phase: Enrolling; Phase 4

Conditions: Medication Related Osteonecrosis of the Jaw

Treatments: Procedure: Surgical resection; Procedure: Minimally invasive surgery with LPRF; Drug: Chlorhexidine mouthwash; Drug: Antibiotics

Study type: Interventional

Funder types: Other

Identifiers

NCT04512638

2018/11482/1

338

Details and patient eligibility

About

BETCON is a pragmatic randomized controlled open-label multi-center study in patients with newly diagnosed stage I-II MRONJ designed to answer the question whether minimally invasive management with LPRF membranes or primary surgical treatment is better than the standard of care of conservative therapy alone. The primary end-point is the time to mucosal healing. Secondary end-points consist of supporting measures of efficacy, patient reported symptoms, quality of life, well-being, and functioning.

Full description

While effective for symptom control and well tolerated, conservative treatment of MRONJ yields highly variable mucosal healing rates ranging between 20 to 50%. In an effort to improve these suboptimal outcomes, many adjunct treatment modalities have been studied, of which the use of minimally invasive surgery with autologous platelet rich plasma (LPRF) to improve wound healing has attracted considerable attention, with reported mucosal closure rates of up to 86% in single arm case series. More recently, improved understanding of the need for pre-operative infection control and adaptation of surgical protocols has renewed the interest in the primary surgical treatment of MRONJ with mucosal closure achieved in up to 90% of patients in some case series.

Therapeutic studies of MRONJ have almost exclusively focused on mucosal healing as the desired end-point of MRONJ treatment, with little or no attention to patient symptoms, quality of life, functioning and well-being during treatment, even though the resolution of MRONJ symptoms and limiting treatment related adverse events may be equally important to patients.

This comparative effectiveness research (CER) study is a randomized controlled open-label multi-center study in patients with newly diagnosed stage I-II MRONJ and is designed to answer the question whether minimally invasive treatment with LPRF membranes or primary surgical treatment improves outcomes when added to the standard of care of conservative treatment alone. The study also incorporates pragmatic design elements and uses patient reported outcomes (PRO) to determine which treatment offers the best humanistic outcomes considering both efficacy and measures of quality of life, functioning, well-being and symptom control. Indeed, this study will not use an investigational new drug (or drug regimen), device, or surgical technique, but rather evaluate their relative efficacy to guide future clinical management. Finally, plasma and saliva will be collected to identify prognostic and predictive biomarkers of outcome.

Enrollment: 125 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• >18 years of age
• Provision of signed informed consent
• A history of at least one administration of, or an ongoing treatment with, a bone modifying agent in dose registered for the prevention of skeletal related events in bone metastatic disease or multiple myeloma
• Diagnosis of stage I-II MRONJ according to AAOMS 2014 criteria not more than 8 weeks prior to the date of screening

Exclusion criteria

• Any prior treatment for MRONJ other than local antiseptic rinses, systemic antibiotics, or analgesics
• Prior radiotherapy to the head and neck region
• Medical contraindication to receive any of the possible study treatments
• Stage III MRONJ characterized by very extensive bone necrosis, pathological fracture, or fistulas to the skin or sinuses
• Multiple MRONJ lesions that cannot be closed in a single surgical procedure

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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125 participants in 3 patient groups

Conservative treatment

Active Comparator group

Description:

Amoxicillin-based antibiotics and chlorhexidine oral rinse. Minor debridement. Primary wound closure is not part of this treatment strategy.

Treatment:

Drug: Antibiotics

Drug: Chlorhexidine mouthwash

Minimally invasive approach + LPRF

Experimental group

Description:

Amoxicillin-based antibiotics and chlorhexidine oral rinse. Minimally-invasive surgical treatment, including sequestrectomy, debridement of soft tissue, and application of LPRF membranes before tension-free wound closure is obtained. Marginal resection of all necrotic bone is not part of this treatment strategy.

Treatment:

Drug: Antibiotics

Drug: Chlorhexidine mouthwash

Procedure: Minimally invasive surgery with LPRF

Primary surgical management

Experimental group

Description:

Amoxicillin-based antibiotics and chlorhexidine oral rinse. Removal of the necrotic bone without excessive resection of healthy bone. Buccal mucoperiosteal flaps will be used to achieve a tension-free mucosal coverage.

Treatment:

Procedure: Surgical resection

Drug: Antibiotics

Drug: Chlorhexidine mouthwash