Pentoxifylline + Tocopherol for Osteonecrosis of the Jaw

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Washington

Must be taking: Antiresorptives

Must not be taking: Oral anticoagulants, CYP1A2 inhibitors

Disqualifiers: Radiation therapy, Cardiac arrhythmia, Renal failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking additional vitamin E if you decide to enroll. If you are taking oral anticoagulants, you cannot participate. You should also discuss with the study team if you are taking aspirin or other medications that affect blood clotting to see if the study is a good fit for you.

What data supports the effectiveness of the drug pentoxifylline and tocopherol for osteonecrosis of the jaw?

Research shows that using pentoxifylline and tocopherol together can help heal the jaw in patients with medication-related osteonecrosis. In a study, patients who received these drugs had better healing outcomes compared to those who did not, with fewer relapses and complications. ^{1 2 3 4 5}

Is the combination of pentoxifylline and tocopherol safe for humans?

The studies reviewed focus on the use of pentoxifylline and tocopherol for jaw conditions, but they do not specifically address safety concerns. However, these medications have been used in other conditions, suggesting they are generally considered safe for human use. ^{2 3 4 5 6}

How does the drug Pentoxifylline + Tocopherol differ from other treatments for osteonecrosis of the jaw?

Pentoxifylline and tocopherol are unique because they combine antioxidant and antifibrotic properties, which help in healing the jaw bone and mucosa, especially in cases related to medication use. This combination has shown promising results in both preventing and treating osteonecrosis of the jaw, particularly after dental extractions, compared to traditional surgical approaches alone. ^{1 2 3 4 5}

What is the purpose of this trial?

The overall purpose of this project is to answer the following clinical question: Among Medication-Related Osteonecrosis of the Jaw (MRONJ) patients, do those who are treated with the Pentoxifylline and Tocopherol (PENTO) regimen and standard of care, when compared to those treated with standard of care alone, have decreased areas of exposed bone after one year of treatment?

Research Team

Jasjit Dillon, DDS, MBBS

Principal Investigator

University of Washington

Eligibility Criteria

This trial is for individuals with Medication-related Osteonecrosis of the Jaw (MRONJ) who have been treated with antiresorptive medications. They must not have tumors in the jaw, severe heart or kidney issues, bleeding disorders, or be pregnant. Participants should not be on certain drugs like CYP1A2 inhibitors and must agree to avoid vitamin E supplements during the study.

Inclusion Criteria

I have stage 1, 2, or 3 jawbone damage related to medication use.

I do not have a tumor in my jaw.

I understand the details of the clinical trial and can agree to participate.

Exclusion Criteria

My kidneys are not working well (severe renal failure).

I am currently taking medication that affects my liver enzyme CYP1A2.

I have a heart condition related to poor blood flow.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the PENTO regimen or standard of care for 12 months

12 months

Monthly visits for monitoring and assessment

Interim Analysis

Interim analyses are performed at 3 and 6 months to assess safety and efficacy

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Pentoxifylline
• Placebo
• Tocopherol

Trial Overview The trial tests if adding Pentoxifylline and Tocopherol (PENTO) to standard care is more effective than standard care alone in reducing exposed bone areas in MRONJ patients after one year. Patients are randomly assigned to receive either PENTO plus standard care or a placebo with standard care.

Participant Groups

Group I: Standard of Care + PENTO Experimental Treatment 2 Interventions

The current standard of care for MRONJ as outlined by the American Association of Oral and Maxillofacial Surgeons position paper based on stage of disease (Ruggiero 2014) AND PENTO regimen consisting of 400mg pentoxifylline (PTX) and 400IU tocopherol twice-daily PO for a total of 800mg/day PTX and 800 IU/day tocopherol

Group II: Standard of Care Placebo Group 1 Intervention

The current standard of care for MRONJ as outlined by the American Association of Oral and Maxillofacial Surgeons position paper based on stage of disease (Ruggiero 2014). Placebo drugs to be taken in the control group 2 pills BID.

Pentoxifylline is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Trental for:

• Intermittent claudication

Approved in Canada as Trental for:

• Intermittent claudication

Approved in European Union as Trental for:

• Intermittent claudication

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

New York Center for Orthognathic and Maxillofacial Surgery

Collaborator

Trials

1

Recruited

100+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Findings from Research

In a case series of six patients with bisphosphonate-associated osteonecrosis (BON), treatment with pentoxifylline and α-tocopherol, alongside antimicrobial therapy, resulted in a significant 74% reduction in bony exposure and improved symptom control over an average follow-up of 10 months.

The findings suggest that pentoxifylline and α-tocopherol could be an effective management strategy for BON, indicating the need for further controlled trials to validate these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of bisphosphonate-associated osteonecrosis: pentoxifylline and tocopherol in addition to antimicrobial therapy. An initial case series. Epstein, MS., Wicknick, FW., Epstein, JB., et al.[2013]

In a case series of seven patients with refractory medication-related osteonecrosis of the jaw (MRONJ), treatment with pentoxifylline and tocopherol (PENT-E) over an average of 16.8 months resulted in symptom relief and radiographic evidence of new bone formation in all patients.

PENT-E was well tolerated, suggesting it may be a safe and effective adjunct treatment for managing MRONJ in patients with metastatic bone disease or multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pentoxifylline and tocopherol in the management of cancer patients with medication-related osteonecrosis of the jaw: an observational retrospective study of initial case series. Owosho, AA., Estilo, CL., Huryn, JM., et al.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes of a Pharmacological Protocol with Pentoxifylline and Tocopherol for the Management of Medication-Related Osteonecrosis of the Jaws (MRONJ): A Randomized Study on 202 Osteoporosis Patients. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Effect of pentoxifylline and α-tocopherol on medication-related osteonecrosis of the jaw in rats: Before and after dental extraction. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Management of bisphosphonate-associated osteonecrosis: pentoxifylline and tocopherol in addition to antimicrobial therapy. An initial case series. [2013]

4. Germany pubmed.ncbi.nlm.nih.gov

Pentoxifylline and tocopherol as prophylaxis for osteonecrosis of the jaw due to bone-modifying agents in patients with cancer submitted to tooth extraction: a case series. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Pentoxifylline and tocopherol in the management of cancer patients with medication-related osteonecrosis of the jaw: an observational retrospective study of initial case series. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Systematic review of the use of pentoxifylline and tocopherol for the treatment of medication-related osteonecrosis of the jaw. [2020]