modified PENTOCLO (mPENTOCLO): 4-week "pre-treatment" phase consisting of 2 g daily of Amoxicillin+Clavulanic acid 875/125 mg (1 g morning and night), 1 g ciprofloxacin (500 mg morning and night) and 50 mg Fluconazole daily (morning), taken orally by the patient.
This is followed by an additional 11 months (12 months total) "treatment" phase consisting of 800 mg pentoxifylline (400 mg morning and night) and 800 IU tocopherol (400 IU morning and night) taken orally 5 days per week (Monday to Friday with no medications on Saturday and Sunday). If the patient deteriorates (i.e., worsening of ORN T 6 or 9-month follow-up) then clodronate 1600 mg once daily (Monday to Friday) for the rest of the study period will be added.
sham mPENTOCLO: 4-week "pre-treatment" phase consisting of 2 g daily of Amoxicillin+Clavulanic acid 875/125 mg (1 g morning and night), 1 g ciprofloxacin (500 mg morning and night) and 50 mg Fluconazole daily (morning), taken orally by the patient.
This is followed by an additional 11 months (12 months total) of sham "treatment" phase (placebo).
Study summary
Radiation is commonly used to treat cancer in the head and neck, however, this can lead to a serious complication called osteoradionecrosis (ORN), where there is necrotic (dead) open bone inside or outside of the mouth. This complication is difficult to treat, involves large healthcare costs, and can have devastating effects on quality of life.
Two common adjuncts used in treatment of ORN are hyperbaric oxygen therapy (HBOT), which may requires up to 60 treatments at a specialized clinic where patients are treated with high concentrations of oxygen using special chambers, and a less complex option called PENTOCLO which involves treating patients with several antibiotics followed by a combination of other oral medications taken for at least 1 year.
This pilot study will be guide the design of a definitive trial to examine if the combination of HBOT and a modified PENTOCLO protocol together is better than the current standard treatment of HBOT alone. Outcomes will include pain, side effects and the need for surgery in patients with ORN. Specifically, the results of this small, pilot study will help to inform the design of a future larger study.
Eligibility
Sex
ALL
Min age
—
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Diagnosis of mandibular ORN after completion of radiotherapy
* ORN will be defined as "an area of exposed devitalized irradiated bone (\> 20 mm2)"; minor bone spicules (MBS) (\< 20 mm2) in the absence of radiographic abnormality, will be considered clinically insignificant
* Has no contraindications for undergoing hyperbaric oxygen therapy as assessed by a Hyperbaric Physician, and is willing to commit the time to undergo 60 sessions
* Negative Human Chronic Gonadotropin (hCG) screening test at baseline (for female patients of reproductive age not practicing medically acceptable methods of birth control (e.g., hormonal contraceptives, implants, injectables, intrauterine device (IUD), intrauterine system (IUS), vasectomy and bilateral tubal ligation)
* Baseline in-date ECG (within 60 days prior to enrolment)
* Age ≥ 18
Exclusion Criteria:
* Inability to give informed consent
* Previous treatment for ORN (PENTOCLO, HBOT or surgery)
* Major surgical procedure planned (more extensive than sequestrectomy)
* Severe trismus and inability to obtain intraoral photographs
* Contraindications for HBOT: pneumothorax, bullous disease, uncontrolled hypertension, uncontrolled epilepsy, claustrophobia
* Contraindications to mPENTOCLO (inability to swallow medication; pregnancy or lactating; allergy to any study drug; currently on oral anticoagulants; hemorrhagic/coagulation disorder; Vitamin K deficiency; active unresolved cardiac disease; severe liver or kidney disease (CrCl\<30 mL/min))
* Known QT prolongation as documented on an in-date ECG (within 60 days prior to enrolment) are excluded. Patients with the QTc prolongation associated with a correctable cause (e.g., electrolyte imbalance or drug-induced), and corrected QTc prior to enrolment into the study as documented on 12 lead ECG will be eligible for inclusion
* Patients requiring concurrent use of medications known to significantly prolong the QT interval with a high risk of clinical impact (e.g., erythromycin, cisapride, astemizole, pimozide or quinidine) are excluded unless safe discontinuation or substitution of these medications is feasible prior to initiation of the study
* Patients on medication with a potential but low risk of QTc prolongation (e.g., ondansetron, SSRIs) may be included if a post-initiation ECG conducted within 24-48 hours of starting ciprofloxacin or fluconazole confirms that there is no significant QTc prolongation
* History of cholestatic jaundice/hepatic dysfunction associated with amoxicillin-clavulanate
* Moderate to severe active liver disease (class B or C Pugh-Child Score) or active liver disease with significant acute elevation of LFT values
* History of myasthenia gravis
* Patients with a history of nontraumatic tendon disorders with severe functional impairment (i.e., significant swelling of the affected tendon, or partial tendon tear documented on clinical examination or imaging)
* Patients who have previously experienced peripheral neuropathy due to exposure to antibiotics
* Smokers, high alcohol intake (average of \>2 standard drinks per day), sepsis, severe undernourishment and severe immunodeficiency conditions (e.g. HIV, autoimmune disease, immune-compromised)
* Persistent or recurrent cancer and active neoplastic pathology will be excluded
* Patients with documented Vitamin K deficiency
* Patients taking additional Vitamin E
* Patients with concomitant prescription of anti-resorptive or anti-angiogenic medications (e.g. risedronate, alendronate, aIbandronate, zoledronic acid, pamidronate, etidronate or prescription of denosusamab, etc.)
* Patients diagnosed with retinitis pigmentosa
* Patients diagnosed with clinically significant anemia
Primary outcome measure(s)
Recruitment and adherence to protocol (process) — Pilot study (including 12-month follow-up) Recruitment of two subjects per month on average over 12 months
Recruitment and adherence to protocol (process) — Pilot study (including 12-month follow-up) At least 70% of all eligible patients are recruited
Recruitment and adherence to protocol (process) — Pilot study (including 12-month follow-up) More than 80% of all recruited subjects complete 60 sessions of HBOT (20/24)
Recruitment and adherence to protocol (process) — Pilot study (including 12-month follow-up) More than 80% of patients in mPENTOCLO group complete mPENTOCLO protocol (10/12)
Recruitment and adherence to protocol (process) — Pilot study (including 12-month follow-up) 80% 12-month follow-up rate (20/24)
Feasibility (resource) - Time — Pilot study (including 12-month follow-up) Investigators to keep logs of time required to perform study related work
Feasibility (resource) - Cost — Pilot study (including 12-month follow-up) Cost of study including research support and healthcare resource costs per patient
Trial sites (1)
Facility
City
Region
Status
Sunnybrook Health Sciences Centre
Toronto
Ontario
Recruiting
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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