OsteoradionecrosisPhase 4PENTONCT02368457
Management of Mandibular ORN: PENTO as Medical Treatment
A Phase 4 study testing Pentoxifylline and Tocopherol in people with Osteoradionecrosis, run by Hospital Vall d'Hebron at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Osteoradionecrosis
- What is being tested?
- Pentoxifylline and Tocopherol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSpain
- Study dates
- Feb 2016to 1 Jan 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Advances in the Management of Mandibular Osteoradionecrosis: Pentoxifylline and Tocopherol as Medical Treatment
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.
Read the detailed description
Mandibular osteoradionecrosis which occurs after the use of radiation therapy for the treatment of head and neck cancer remains being the most problematic and irreversible complication despite its low incidence with no medical treatment to limit or reduce symptoms.
Clinical trials conducted to date have shown a significant scientific evidence that the treatment with pentoxifylline + tocopherol achieves a certain effectiveness in the treatment of the tissue fibrosis that have been irradiated based on the properties of this drugs in increased tissue oxygenation and their antioxidant effect.
The aim of this study is to determine if there is a clinical improvement of mandibular osteoradionecrosis using Pentoxifylline in combination with Tocopherol as treatment because, currently, there is no effective treatment to achieve bone healing and/or a symptomatic improvement.
- Conditions
- Osteoradionecrosis
- Being tested
- Pentoxifylline and Tocopherol
- 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
- Medical subject headings
- Osteoradionecrosis, Wounds and Injuries, Osteonecrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pentoxifylline and TocopherolDrug
Also called PENTO
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pentoxifylline and Tocopherol |
| CONTROL | No intervention | No drug treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to 1, 3, 6, and 9 months of starting treatment
Secondary outcomes (1)
Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale
Evaluation of symptoms improvement using the LENT-SOMA scale (Late Effect Normal Tissue Task Force / Subjective, Objective, Management, Analytic scale).
To examine the LENT/SOMA scale prospectively using interviews and questionnaires
Assessments were made from baseline to 1, 3, 6 and 9 months of starting treatments. The acceptability and feasibility of using the scales was examined using compliance in completion of the questionnaires.
Maximum score: 36 Minimum score: 0
Questionnaires have been completed for 24 patients after treatment. Higher values represents worse outcome.
Scale categories:
Subjective: pain, nutritional problems, difficulty in mouth openning. Objective: bone exposure, trismus, Management: analgesic treatment, oral treatment, nutrition. Analytic: radiological findings.
Measured: From baseline to 1,3, 6, 9 months of starting treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2015 (estimated)
- Study startFeb 2016
- Primary completionFeb 2016
- Study completion1 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for OsteoradionecrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Vall d'Hebron
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Miriam Martos-Fernandez, Hospital Vall d'Hebron
- Investigators
- Miriam Martos-Fernandez, MD, Principal investigator, Oral and Maxillofacial Surgery (Vall d'Hebrón Hospital)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02368457
- Sponsor's protocol ID
- ORN-2014-16
- Acronym
- PENTO
- Status last verified
- Feb 2018
- First submitted
- 10 Feb 2015
- Last updated
- 22 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 24993781Delanian 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.
PubMed 20638190Delanian 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.
PubMed 15641107
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Advances in the Management of Mandibular Osteoradionecrosis: Pentoxifylline and Tocopherol as Medical Treatment
- ClinicalTrials.gov ID
- NCT02368457
- Acronym / sponsor ID
- PENTO / ORN-2014-16
- Conditions
- Osteoradionecrosis
- Keywords
- Mandibular osteoradionecrosis, Tocopherol, pentoxifylline, vitamine E, wounds and injuries, antioxidants, free radical scavengers, radiation-protective agents
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Hospital Vall d'HebronUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- Feb 2016 (actual)
- Study completion
- 1 Jan 2018 (actual)
- First posted
- 23 Feb 2015 (estimated)
- Results
- Posted 20 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Mandibular osteoradionecrosis which occurs after the use of radiation therapy for the treatment of head and neck cancer remains being the most problematic and irreversible complication despite its low incidence with no medical treatment to limit or reduce symptoms.
Clinical trials conducted to date have shown a significant scientific evidence that the treatment with pentoxifylline + tocopherol achieves a certain effectiveness in the treatment of the tissue fibrosis that have been irradiated based on the properties of this drugs in increased tissue oxygenation and their antioxidant effect.
The aim of this study is to determine if there is a clinical improvement of mandibular osteoradionecrosis using Pentoxifylline in combination with Tocopherol as treatment because, currently, there is no effective treatment to achieve bone healing and/or a symptomatic improvement.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pentoxifylline and Tocopherol | Experimental | Drug: Pentoxifylline and TocopherolDrug: pentoxifylline with tocopherol Combination of pentoxifylline and tocopherol during a minimum of 6 months and a maximum of 24 months. |
| CONTROL | No intervention | –No drug treatment |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pentoxifylline and TocopherolAlso: PENTOpentoxifylline 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). | Drug | Pentoxifylline and Tocopherol |
Primary outcome
Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG).
Time frame: From baseline to 1, 3, 6, and 9 months of starting treatment
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.
1 secondary outcome
Clinical Symptoms Evaluation, Measured Using the LENT-SOMA Scale
Time frame: From baseline to 1,3, 6, 9 months of starting treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24993781Robard 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.
- Background: PubMed 20638190Delanian 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.
- Background: PubMed 15641107Delanian 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miriam Martos-Fernandez, MD principal investigator
Oral and Maxillofacial Surgery (Vall d'Hebrón Hospital)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pentoxifylline and Tocopherol in people with Osteoradionecrosis, run by Hospital Vall d'Hebron at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone and/or Tissue Healing as Measured With the Classification of ORN Stages, Area of Bone Exposed (mm2) and Radiological Findings (OPG). (time frame: From baseline to 1, 3, 6, and 9 months of starting treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02368457, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2018.