Clinical trial NCT04512638: Best Treatment Choice for Osteonecrosis of the Jaw
Official title: A Multicenter Randomized Controlled Open-label Trial of Conservative Management Versus Minimally Invasive Treatment With Leukocyte- and Platelet-rich Fibrin Versus Primary Surgery in Patients With Newly Diagnosed Osteonecrosis of the Jaw
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Medication Related Osteonecrosis of the Jaw
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
Collaborators: name: Kom Op Tegen Kanker
First posted: 2020-08-13
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to confirmed mucosal healing
timeFrame: 12 months
Secondary outcomes:
measure: Mucosal closure
timeFrame: 6 months
measure: Time to MRONJ healing
timeFrame: 12 months
measure: Relapse rate of MRONJ
timeFrame: 12 months
measure: Antibiotics use
timeFrame: 12 months
measure: Evolution of cancer health-related quality-of-life
timeFrame: 12 months
measure: Evolution of general health status
timeFrame: 12 months
measure: Evolution of oral health-specific quality-of-life
timeFrame: 12 months
Other outcomes:
measure: Treatment related adverse events
timeFrame: Through study completion, an average of 1 year
measure: Quality-adjusted Time Without Symptoms and Toxicity (Q-TWiST)
timeFrame: Through study completion, an average of 1 year
Locations:
city: Antwerp
country: Belgium
facility: ZNA Middelheim
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Sint Niklaas
country: Belgium
facility: AZ Nikolaas
Study officials:
affiliation: University Hospital, Antwerp
name: Tim Van den Wyngaert, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beth-Tasdogan NH, Mayer B, Hussein H, Zolk O, Peter JU. Interventions for managing medication-related osteonecrosis of the jaw. Cochrane Database Syst Rev. 2022 Jul 12;7(7):CD012432. doi: 10.1002/14651858.CD012432.pub3.