Clinical trial of the non-surgical management of radiotherapy damage to the lower jaw

Phase 2

• Conditions: Osteoradionecrosis (bone death caused by irradiation); Oral Health

• Registration Number: ISRCTN34217298
• Lead Sponsor: niversity of Liverpool

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-11-11
• Last Update Posted: 22 July 2024
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. A diagnosis of mandibular ORN
2. Patients considered suitable for medical management
3. Written and informed consent obtained from participant and agreement of participant to comply with the requirements of the study
4. Aged 18 years and over

Exclusion Criteria

Current exclusion criteria as of 09/01/2024:

1. Cannot swallow tablets
2. Prior treatment with PENTOCLO or any element thereof within 12 months of the date of randomisation
3. Very early ORN (<20 mm² exposed bone) occurring within 12 months of a dental extraction or other dentoalveolar operation (‘Minor Bone Spicules’)
4. Mandibular pathological fracture secondary to ORN
5. Indication for mandible resection - i.e. patient for whom the severity of their ORN symptoms already constitute an indication for mandible resection and reconstruction. Typically, these symptoms will include severe pain, repeated infections, significant mobile pathological fracture or distressing fistula)
6. Patient has had definitive resection / reconstruction for mandibular ORN -i.e. no longer has exposed necrotic bone present.
7. Pregnancy
8. Lactation
9. Age <18 years
10. Acute infection at site of the necrotic bone.
11. Contraindications to PENTOCLO medications:
11.1. Known hypersensitivity, allergy or anaphylaxis to pentoxifylline, tocopherol or sodium clodronate
11.2. Treated hypotension
11.3. Severe coronary artery disease, defined as grade IV of the Canadian Cardiology Society Angina Grading
11.4. Severe atrial fibrillation, defined as grade 4 on modified CCC-SAF
11.5. Myocardial infarction within 6 months
11.6. Prior history of extensive retinal haemorrhage
11.7. Prior history of intracranial bleeding
11.8. Impaired renal function (Creatinine clearance <30 ml/minute, will be formally assessed only if U&E out of reference)
11.9. Severe liver failure (class B or C Pugh-Child Score, will be formally assessed only if LFT values, out of reference)
11.10. Concomitant prescription of anti-platelet agents: clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, NSAIDs, acetylsalicylates (ASA/LAS) including aspirin >75 mg*, ticlopidine, dipyridamole. (*low dose =75 mg aspirin is permitted)
11.11. Concomitant prescription of ketorolac, cimetidine, ciprofloxacin, theophylline, estramustine phosphate
11.12. Hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency
11.13. Concomitant prescription other bisphosphonates e.g. risedronate, alendronate, aIbandronate, zoledronic acid, pamidronate, etidronate or prescription of denosusamab
11.14. Concomitant prescription of aminoglycoside antibiotics e.g. gentamicin, tobramycin, amikacin, plazomicin, streptomycin, neomycin, paromomycin

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Previous exclusion criteria:

1. Cannot swallow tablets
2. Prior treatment with PENTOCLO or any element thereof within 12 months of the date of randomisation
3. Very early ORN (<20 mm² exposed bone) occurring within 12 months of a dental extraction or other dentoalveolar operation (‘Minor Bone Spicules’ see flowchart below)
4. Mandibular pathological fracture secondary to ORN
5. Extra-oral communicating fistula secondary to ORN
6. Prior surgery/jaw resection
7. Pregnancy
8. Lactation
9. Age <18 years
10. Acute infection at site of the necrotic bone.
11. Contraindications to PENTOCLO medications:
11.1. Known hypersensitivity, allergy or anaphylaxis to pentoxifylline, tocopherol or sodium clodronate
11.2. Treated hypotension
11.3. Severe coronary artery disease, defined as grade IV of the Canadian Cardiology Society Angina Grading
11.4. Severe atrial fibrillation, defined as grade 4 on modified CCC-SAF
11.5. Myocardial infarction within 6 months
11.6. Prior history of extensive retinal haemorrhage
11.7. Prior histo

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Time to healing (defined as the complete elimination of exposed bone without the need for surgery), measured every 3 months following randomisation until the end of the trial for that patient