Best Treatment Choice for Osteonecrosis of the Jaw

NCT ID: NCT04512638

Last Updated: 2023-05-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-01
• Study Completion Date: 2026-01-01

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.

Conditions

Medication Related Osteonecrosis of the Jaw

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Conservative treatment

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

Group Type: ACTIVE_COMPARATOR

Antibiotics

Intervention Type: DRUG

Antibiotic treatment is the same in all groups.

Monotherapy for 4 weeks with:

No penicillin contra-indication

• Amoxicillin-clavulanate 875mg tid PO Penicillin contra-indication or intolerance
• Clindamycin 300mg tid PO

After 4 weeks patients will be switched to consolidation antibiotics:

No penicillin contra-indication

• Amoxicillin 1g bid PO Penicillin contra-indication or intolerance
• Clindamycin 300mg tid PO

Antibiotic treatment can be discontinued after 4 weeks when the MRONJ lesions has healed.

Chlorhexidine mouthwash

Intervention Type: DRUG

Patients in all treatment groups will be prescribed aqueous chlorhexidine 0.12% tid rinse for 2 weeks, with subsequent switch to 0.05% for the duration of the study or until healing of the MRONJ lesion has occurred.

Minimally invasive approach + LPRF

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.

Group Type: EXPERIMENTAL

Antibiotics

Intervention Type: DRUG

Antibiotic treatment is the same in all groups.

Monotherapy for 4 weeks with:

No penicillin contra-indication

• Amoxicillin-clavulanate 875mg tid PO Penicillin contra-indication or intolerance
• Clindamycin 300mg tid PO

After 4 weeks patients will be switched to consolidation antibiotics:

No penicillin contra-indication

• Amoxicillin 1g bid PO Penicillin contra-indication or intolerance
• Clindamycin 300mg tid PO

Antibiotic treatment can be discontinued after 4 weeks when the MRONJ lesions has healed.

Chlorhexidine mouthwash

Intervention Type: DRUG

Patients in all treatment groups will be prescribed aqueous chlorhexidine 0.12% tid rinse for 2 weeks, with subsequent switch to 0.05% for the duration of the study or until healing of the MRONJ lesion has occurred.

Minimally invasive surgery with LPRF

Intervention Type: PROCEDURE

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.

Primary surgical management

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.

Group Type: EXPERIMENTAL

Antibiotics

Intervention Type: DRUG

Antibiotic treatment is the same in all groups.

Monotherapy for 4 weeks with:

No penicillin contra-indication

• Amoxicillin-clavulanate 875mg tid PO Penicillin contra-indication or intolerance
• Clindamycin 300mg tid PO

After 4 weeks patients will be switched to consolidation antibiotics:

No penicillin contra-indication

• Amoxicillin 1g bid PO Penicillin contra-indication or intolerance
• Clindamycin 300mg tid PO

Antibiotic treatment can be discontinued after 4 weeks when the MRONJ lesions has healed.

Chlorhexidine mouthwash

Intervention Type: DRUG

Patients in all treatment groups will be prescribed aqueous chlorhexidine 0.12% tid rinse for 2 weeks, with subsequent switch to 0.05% for the duration of the study or until healing of the MRONJ lesion has occurred.

Surgical resection

Intervention Type: PROCEDURE

Primary surgical management consisting of the removal of the necrotic bone without excessive resection of healthy bone. Buccal mucoperiosteal flaps will be used to achieve a tension-free mucosal coverage.

Interventions

Antibiotics

Antibiotic treatment is the same in all groups.

Monotherapy for 4 weeks with:

No penicillin contra-indication

• Amoxicillin-clavulanate 875mg tid PO Penicillin contra-indication or intolerance
• Clindamycin 300mg tid PO

After 4 weeks patients will be switched to consolidation antibiotics:

No penicillin contra-indication

• Amoxicillin 1g bid PO Penicillin contra-indication or intolerance
• Clindamycin 300mg tid PO

Antibiotic treatment can be discontinued after 4 weeks when the MRONJ lesions has healed.

Intervention Type: DRUG

Chlorhexidine mouthwash

Patients in all treatment groups will be prescribed aqueous chlorhexidine 0.12% tid rinse for 2 weeks, with subsequent switch to 0.05% for the duration of the study or until healing of the MRONJ lesion has occurred.

Intervention Type: DRUG

Minimally invasive surgery with LPRF

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.

Intervention Type: PROCEDURE

Surgical resection

Primary surgical management consisting of the removal of the necrotic bone without excessive resection of healthy bone. Buccal mucoperiosteal flaps will be used to achieve a tension-free mucosal coverage.

Intervention Type: PROCEDURE

Other Intervention Names

amoxicillin; chlorhexidine

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kom Op Tegen Kanker

OTHER

Sponsor Role: collaborator

Tim Van den Wyngaert

OTHER

Sponsor Role: lead

Responsible Party

Tim Van den Wyngaert

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Tim Van den Wyngaert, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Antwerp

Locations

ZNA Middelheim

Antwerp, , Belgium

Site Status: RECRUITING

Antwerp University Hospital

Edegem, , Belgium

Site Status: RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status: RECRUITING

AZ Nikolaas

Sint-Niklaas, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Tim Van den Wyngaert, MD, PhD

Role: CONTACT

tim.van.den.wyngaert@uza.be

003238213568

Facility Contacts

Olivier Lenssen, MD, DDS

Role: primary

Tim Van den Wyngaert, MD, PhD

Role: primary

Constantinus Politis, MD, DDS, PhD

Role: primary

Vincent Lenaerts, MD, DDS

Role: primary

References

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.

Reference Type: DERIVED

PMID: 35866376 (View on PubMed)

Related Links

http://www.betcon.be

Trial website

Other Identifiers

338

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018/11482/1

Identifier Type: -

Identifier Source: org_study_id