Best Treatment Choice for Osteonecrosis of the Jaw (BETCON)
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| ClinicalTrials.gov Identifier: NCT04512638 |
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Recruitment Status :
Not yet recruiting
First Posted : August 13, 2020
Last Update Posted : August 13, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Medication Related Osteonecrosis of the Jaw | Drug: Antibiotics Drug: Chlorhexidine mouthwash Procedure: Minimally invasive surgery with LPRF Procedure: Surgical resection | Phase 4 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 125 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Estimated Study Start Date : | October 1, 2020 |
| Estimated Primary Completion Date : | October 1, 2023 |
| Estimated Study Completion Date : | January 1, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Conservative treatment
Amoxicillin-based antibiotics and chlorhexidine oral rinse. Minor debridement. Primary wound closure is not part of this treatment strategy.
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Drug: Antibiotics
Antibiotic treatment is the same in all groups. Monotherapy for 4 weeks with: No penicillin contra-indication
After 4 weeks patients will be switched to consolidation antibiotics: No penicillin contra-indication
Antibiotic treatment can be discontinued after 4 weeks when the MRONJ lesions has healed. Other Name: amoxicillin 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.
Other Name: chlorhexidine |
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Experimental: 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.
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Drug: Antibiotics
Antibiotic treatment is the same in all groups. Monotherapy for 4 weeks with: No penicillin contra-indication
After 4 weeks patients will be switched to consolidation antibiotics: No penicillin contra-indication
Antibiotic treatment can be discontinued after 4 weeks when the MRONJ lesions has healed. Other Name: amoxicillin 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.
Other Name: chlorhexidine Procedure: 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. |
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Experimental: 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.
|
Drug: Antibiotics
Antibiotic treatment is the same in all groups. Monotherapy for 4 weeks with: No penicillin contra-indication
After 4 weeks patients will be switched to consolidation antibiotics: No penicillin contra-indication
Antibiotic treatment can be discontinued after 4 weeks when the MRONJ lesions has healed. Other Name: amoxicillin 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.
Other Name: chlorhexidine 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. |
- 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.
- Mucosal closure [ Time Frame: 6 months ]Proportion of patients with mucosal closure 6 months after randomization
- Time to MRONJ healing [ Time Frame: 12 months ]Time to resolution of MRONJ symptoms after start of treatment
- Relapse rate of MRONJ [ Time Frame: 12 months ]Incidence of patients with relapse at the site of MRONJ
- Antibiotics use [ Time Frame: 12 months ]Total duration of exposure to antimicrobial agents
- Evolution of cancer health-related quality-of-life [ Time Frame: 12 months ]Changes over time as measured with the EORTC QLQ-C30 questionnaire.
- Evolution of general health status [ Time Frame: 12 months ]Changes over time as measured with the EUROQOL 5D (EQ-5D-5L) questionnaire.
- Evolution of oral health-specific quality-of-life [ Time Frame: 12 months ]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.
- Treatment related adverse events [ Time Frame: Through study completion, an average of 1 year ]Incidence and intensity of treatment emergent adverse events
- Quality-adjusted Time Without Symptoms and Toxicity (Q-TWiST) [ Time Frame: Through study completion, an average of 1 year ]This analysis analysis considers three health states: toxicity, time without symptoms and toxicity (TWiST), and relapse. The toxicity state comprises the total time after randomization and before relapse of MRONJ symptoms spent with toxicity, regardless of when the toxicity started or gaps between toxicities. The TWiST state is defined as the time of relapse of MRONJ symptoms minus time with toxicities. The duration of the relapse state is defined as overall survival time minus time to relapse of MRONJ symptoms.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04512638
| Contact: Tim Van den Wyngaert, MD, PhD | 003238213568 | tim.van.den.wyngaert@uza.be |
| Belgium | |
| ZNA Middelheim | |
| Antwerp, Belgium, 2020 | |
| Contact: Olivier Lenssen, MD, DDS | |
| Antwerp University Hospital | |
| Edegem, Belgium, 2650 | |
| Contact: Tim Van den Wyngaert, MD, PhD | |
| UZ Leuven | |
| Leuven, Belgium, 3000 | |
| Contact: Constantinus Politis, MD, DDS, PhD | |
| AZ Nikolaas | |
| Sint Niklaas, Belgium, 9100 | |
| Contact: Vincent Lenaerts, MD, DDS | |
| Principal Investigator: | Tim Van den Wyngaert, MD, PhD | University Hospital, Antwerp |
| Responsible Party: | Tim Van den Wyngaert, Principal Investigator, University Hospital, Antwerp |
| ClinicalTrials.gov Identifier: | NCT04512638 |
| Other Study ID Numbers: |
2018/11482/1 338 ( Registry Identifier: EDGE ) |
| First Posted: | August 13, 2020 Key Record Dates |
| Last Update Posted: | August 13, 2020 |
| Last Verified: | August 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Osteonecrosis Bone Diseases Musculoskeletal Diseases Necrosis Pathologic Processes Anti-Bacterial Agents Amoxicillin |
Chlorhexidine Chlorhexidine gluconate Anti-Infective Agents Anti-Infective Agents, Local Disinfectants Dermatologic Agents |