Medication Related Osteonecrosis of the JawPhase 4BETCONNCT04512638
Best Treatment Choice for Osteonecrosis of the Jaw
A Phase 4 study testing Antibiotics, Chlorhexidine mouthwash and Minimally invasive surgery with LPRF in people with Medication Related Osteonecrosis of the Jaw, run by Tim Van den Wyngaert at 4 sites in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Medication Related Osteonecrosis of the Jaw
- What is being tested?
- Antibiotics, Chlorhexidine mouthwash and Minimally invasive surgery with LPRF
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 4 sitesBelgium
- Study dates
- 1 Jan 2021to 1 Jan 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >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
Who cannot join
- 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 locations and contacts
4 sites in 1 country.
Belgium4 sites, 4 recruiting
- Recruiting
ZNA Middelheim
Antwerp, 2020
Olivier Lenssen, MD, DDS
- Recruiting
Antwerp University Hospital
Edegem, 2650
Tim Van den Wyngaert, MD, PhD
- Recruiting
UZ Leuven
Leuven, 3000
Constantinus Politis, MD, DDS, PhD
- Recruiting
AZ Nikolaas
Sint-Niklaas, 9100
Vincent Lenaerts, MD, DDS
About this study
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
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.
Read the 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.
- Being tested
- Antibiotics, Chlorhexidine mouthwash, Minimally invasive surgery with LPRF, Surgical resection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AntibioticsDrug
Also called amoxicillin
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 mouthwashDrug
Also called chlorhexidine
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 LPRFProcedure or surgery
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.
Surgical resectionProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Conservative treatment | Active comparator | Amoxicillin-based antibiotics and chlorhexidine oral rinse. Minor debridement. Primary wound closure is not part of this treatment strategy. Receives: Drug: Antibiotics; Drug: 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. Receives: Drug: Antibiotics; Drug: Chlorhexidine mouthwash; Procedure: 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. Receives: Drug: Antibiotics; Drug: Chlorhexidine mouthwash; Procedure: Surgical resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (7)
Mucosal closure
Proportion of patients with mucosal closure 6 months after randomization
Measured: 6 months
Time to MRONJ healing
Time to resolution of MRONJ symptoms after start of treatment
Measured: 12 months
Relapse rate of MRONJ
Incidence of patients with relapse at the site of MRONJ
Measured: 12 months
Antibiotics use
Total duration of exposure to antimicrobial agents
Measured: 12 months
Evolution of cancer health-related quality-of-life
Changes over time as measured with the EORTC QLQ-C30 questionnaire.
Measured: 12 months
Evolution of general health status
Changes over time as measured with the EUROQOL 5D (EQ-5D-5L) questionnaire.
Measured: 12 months
Evolution of oral health-specific quality-of-life
Changes over time as measured with the Oral Health Impacts Profile (OHIP-14) and the SWOG0702 Oral Health and Oral Health-related Quality of Life questionnaires.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2020
- Study start1 Jan 2021
- Primary completion1 Oct 2025 (estimated)
- Study completion1 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Medication Related Osteonecrosis of the JawStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tim Van den Wyngaert
- Sponsor type
- University, hospital or other
- Collaborators
- Kom Op Tegen Kanker
- Responsible party
- Sponsor-investigator, Tim Van den Wyngaert, University Hospital, Antwerp
- Investigators
- Tim Van den Wyngaert, MD, PhD, Principal investigator, University Hospital, Antwerp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04512638
- Sponsor's protocol ID
- 2018/11482/1
- Other IDs
- 338, 2018
- Acronym
- BETCON
- Status last verified
- May 2023
- First submitted
- 8 Aug 2020
- Last updated
- 23 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35866376
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04512638
- Acronym / sponsor ID
- BETCON / 2018/11482/1
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 125 participants (estimated)
- Lead sponsor
- Tim Van den WyngaertUniversity, hospital or other
- Collaborators
- Kom Op Tegen Kanker
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 1 Jan 2026 (estimated)
- First posted
- 13 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Conservative treatment | Active comparator | Drug: Antibiotics, Drug: Chlorhexidine mouthwashAmoxicillin-based antibiotics and chlorhexidine oral rinse. Minor debridement. Primary wound closure is not part of this treatment strategy. |
| Minimally invasive approach + LPRF | Experimental | Drug: Antibiotics, Drug: Chlorhexidine mouthwash, Procedure: Minimally invasive surgery with LPRFAmoxicillin-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. |
| Primary surgical management | Experimental | Drug: Antibiotics, Drug: Chlorhexidine mouthwash, Procedure: Surgical resectionAmoxicillin-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- >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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AntibioticsAlso: amoxicillinAntibiotic 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. | Drug | Conservative treatment, Minimally invasive approach + LPRF, Primary surgical management |
| Chlorhexidine mouthwashAlso: chlorhexidinePatients 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. | Drug | Conservative treatment, Minimally invasive approach + LPRF, Primary surgical management |
| Minimally invasive surgery with LPRFMinimally-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. | Procedure or surgery | Minimally invasive approach + LPRF |
| Surgical resectionPrimary 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. | Procedure or surgery | Primary surgical management |
Primary outcome
Time to confirmed mucosal healing
Time frame: 12 months
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.
7 secondary outcomes
Mucosal closure
Time frame: 6 months
Time to MRONJ healing
Time frame: 12 months
Relapse rate of MRONJ
Time frame: 12 months
Antibiotics use
Time frame: 12 months
Evolution of cancer health-related quality-of-life
Time frame: 12 months
Evolution of general health status
Time frame: 12 months
Evolution of oral health-specific quality-of-life
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2023.
- Derived from this study: PubMed 35866376Beth-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.
- Trial websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim Van den Wyngaert, MD, PhD principal investigator
University Hospital, Antwerp
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Antibiotics, Chlorhexidine mouthwash and Minimally invasive surgery with LPRF in people with Medication Related Osteonecrosis of the Jaw, run by Tim Van den Wyngaert at 4 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tim Van den Wyngaert, MD, PhD (003238213568, tim.van.den.wyngaert@uza.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to confirmed mucosal healing (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04512638, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2023.