Management of Mandibular ORN: PENTO as Medical Treatment

NCT02368457 | Completed Phase 4 Results DMC

• 1 other identifier: ORN-2014-16
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Mandibular osteoradionecrosis, despite its low incidence, remains being the most problematic and irreversible complication after head and neck radiotherapy with no medical treatment to limit or reduce symptoms. Different clinical trials have shown a significant scientific evidence that the treatment with pentoxifylline + tocopherol achieves a certain effectiveness in the treatment of the tissue fibrosis. This study proposes to use this drugs to determine if there is healing of mandibular osteoradionecrosis and/or a symptomatic improvement as well.

Conditions

Osteoradionecrosis

Keywords

Mandibular osteoradionecrosis; Tocopherol; pentoxifylline; vitamine E; wounds and injuries; antioxidants; free radical scavengers; radiation-protective agents; vasodilatadors agents; osteonecrosis; mandible; extraoral fistula; exposed bone; necrotic bone; head and neck radiotherapy

Outcome Measures

Primary Outcomes (1)

• Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG).

  Clinical healing assessment as measured with the classification of ORN stages, area of bone exposed (mm2) and radiological findings (OPG). Intraoral bone exposure is measured in mm2.

  From baseline to 1, 3, 6, and 9 months of starting treatment

Secondary Outcomes (1)

• Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale

  From baseline to 1,3, 6, 9 months of starting treatment

Study Arms (2)

Pentoxifylline and Tocopherol

EXPERIMENTAL

Drug: pentoxifylline with tocopherol Combination of pentoxifylline and tocopherol during a minimum of 6 months and a maximum of 24 months.

Drug: Pentoxifylline and Tocopherol

CONTROL

NO INTERVENTION

No drug treatment

Interventions

Pentoxifylline and Tocopherol DRUG

pentoxifylline with tocopherol Pentoxifylline 800 mg/day, oral (1cp 400 mg twice a day) + Vitamin E (alfa-tocopherol) 1000 UI/day, oral (1cp 400UI twice a day + 1cp200UI once a day) during 24 months (maximum).

Also known as: PENTO

Pentoxifylline and Tocopherol

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Over 18 years and under 90 years old.
• Patients who have received radiotherapy after being diagnosed with head and neck cancer and currently are diagnosticated of mandibular osteoradionecrosis (any clinical stage)
• Follow-up for at least a year after the radiation treatment is completed.
• Absence of tumor at the time of recruitment.
• Patients with the capacity to give informed consent

You may not qualify if:

• Allergy or hypersensitivity to Pentoxifylline or others xanthines, or to Tocopherol (vitamin E).
• Patients taking oral anticoagulants (acenocoumarol, warfarin).
• Known hemorrhagic/coagulation disorder.
• Vitamin K deficiency due to any cause.
• Use of estrogens oral contraceptives.
• Serious bleeding or extensive retinal hemorrhage.
• Ischaemic heart diseases, including recent Myocardial Infarction.
• Serious cardiac arrhythmia.
• Severe LIVER DISEASE.
• Severe renal failure (creatinine clearance \<30 mL/min).
• Hypotension.
• Female patients who are pregnant or lactating
• Any other situation or condition that, in the opinion of the INVESTIGATOR, may interfere with optimal PARTICIPATION in the study.

Sponsors & Collaborators

• Hospital Vall d'Hebron: lead

Study Sites (1)

Vall d'Hebrón Hospital

Barcelona, 08035, Spain

Location

Related Publications (3)

• Robard L, Louis MY, Blanchard D, Babin E, Delanian S. Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: preliminary results. Eur Ann Otorhinolaryngol Head Neck Dis. 2014 Dec;131(6):333-338. doi: 10.1016/j.anorl.2013.11.006. Epub 2014 Jun 30.

  PMID: 24993781 BACKGROUND

• Delanian S, Chatel C, Porcher R, Depondt J, Lefaix JL. Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial. Int J Radiat Oncol Biol Phys. 2011 Jul 1;80(3):832-9. doi: 10.1016/j.ijrobp.2010.03.029. Epub 2010 Jul 16.

  PMID: 20638190 BACKGROUND

• Delanian S, Depondt J, Lefaix JL. Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial. Head Neck. 2005 Feb;27(2):114-23. doi: 10.1002/hed.20121.

  PMID: 15641107 BACKGROUND

MeSH Terms

Conditions

Osteoradionecrosis; Wounds and Injuries; Osteonecrosis

Interventions

Pentoxifylline; Tocopherols

Condition Hierarchy (Ancestors)

Radiation Injuries; Bone Diseases; Musculoskeletal Diseases; Necrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vitamin E; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Miriam Martos
• Organization: Oral and Maxillofacial Surgeon

miryam.martos@gmail.com

+34932746179

Study Officials

• Miriam Martos-Fernandez, MD

  Oral and Maxillofacial Surgery (Vall d'Hebrón Hospital)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oral and Maxillofacial Surgeon

Study Record Dates

• First Submitted: February 10, 2015
• First Posted: February 23, 2015
• Study Start: February 1, 2016
• Primary Completion: February 1, 2016
• Study Completion: January 1, 2018
• Last Updated: March 22, 2018
• Results First Posted: December 20, 2016

Record last verified: 2018-02

Locations

ES (1)