NCT04512638

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
125

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Jan 2021

Longer than P75 for phase_4

Geographic Reach
1 country

4 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 8, 2020

Completed
5 days until next milestone

First Posted

Study publicly available on registry

August 13, 2020

Completed
5 months until next milestone

Study Start

First participant enrolled

January 1, 2021

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2025

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2026

Completed
Last Updated

May 23, 2023

Status Verified

May 1, 2023

Enrollment Period

4.8 years

First QC Date

August 8, 2020

Last Update Submit

May 20, 2023

Conditions

Medication Related Osteonecrosis of the Jaw

Outcome Measures

Primary Outcomes (1)

  • Time to confirmed mucosal healing

    Time after randomization until the observation of healed mucosa (without presence of surgical suturing material) at the site of MRONJ, with a first observation of healed mucosa requiring confirmation after 4 weeks.

    12 months

Secondary Outcomes (7)

  • Mucosal closure

    6 months

  • Time to MRONJ healing

    12 months

  • Relapse rate of MRONJ

    12 months

  • Antibiotics use

    12 months

  • Evolution of cancer health-related quality-of-life

    12 months

  • +2 more secondary outcomes

Other Outcomes (2)

  • Treatment related adverse events

    Through study completion, an average of 1 year

  • Quality-adjusted Time Without Symptoms and Toxicity (Q-TWiST)

    Through study completion, an average of 1 year

Study Arms (3)

Conservative treatment

ACTIVE COMPARATOR

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

Drug: AntibioticsDrug: Chlorhexidine mouthwash

Minimally invasive approach + LPRF

EXPERIMENTAL

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.

Drug: AntibioticsDrug: Chlorhexidine mouthwashProcedure: Minimally invasive surgery with LPRF

Primary surgical management

EXPERIMENTAL

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.

Drug: AntibioticsDrug: Chlorhexidine mouthwashProcedure: Surgical resection

Interventions

AntibioticsDRUG

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.

Also known as: amoxicillin
Conservative treatmentMinimally invasive approach + LPRFPrimary surgical management
Chlorhexidine mouthwashDRUG

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.

Also known as: chlorhexidine
Conservative treatmentMinimally invasive approach + LPRFPrimary surgical management
Minimally invasive surgery with LPRFPROCEDURE

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.

Minimally invasive approach + LPRF
Surgical resectionPROCEDURE

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.

Primary surgical management

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \>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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

ZNA Middelheim

Antwerp, 2020, Belgium

RECRUITING

Antwerp University Hospital

Edegem, 2650, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

AZ Nikolaas

Sint-Niklaas, 9100, Belgium

RECRUITING

Related Publications (1)

  • 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.

    PMID: 35866376DERIVED

Related Links

MeSH Terms

Interventions

Anti-Bacterial AgentsAmoxicillinChlorhexidineMinimally Invasive Surgical Procedures

Intervention Hierarchy (Ancestors)

Anti-Infective AgentsTherapeutic UsesPharmacologic ActionsChemical Actions and UsesAmpicillinPenicillin GPenicillinsbeta-LactamsLactamsAmidesOrganic ChemicalsSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsBiguanidesGuanidinesAmidinesSurgical Procedures, Operative

Study Officials

  • Tim Van den Wyngaert, MD, PhD

    University Hospital, Antwerp

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Tim Van den Wyngaert, MD, PhD

CONTACT

003238213568tim.van.den.wyngaert@uza.be

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

August 8, 2020

First Posted

August 13, 2020

Study Start

January 1, 2021

Primary Completion

October 1, 2025

Study Completion

January 1, 2026

Last Updated

May 23, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will not share

Locations

BE(4)