Combination Therapy: Hyperbaric Oxygen and PENTOCLO for Treatment of Osteoradionecrosis of the Mandible

Exclusion Criteria21

• 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