Pentoxifylline and tocopherol (PENTO) in the treatment of MRONJ Formation Targeting the VEGFa Pathway
Jasjit Kaur Dillon is an Associate Clinical Professor and Program Director of Oral and Maxillofacial Surgery at the University of Washington, Seattle. She obtained her dental degrees from the University of Newcastle Upon Tyne (BDS), the University of California San Francisco (DDS) and her medical degree from St Bartholomew’s School of Medicine, University of London (MBBS). She is a member of the Royal College of Surgeons of England (FDSCRCS), the American College of Surgeons (FACS) and is an examiner for the American Board of OMFS. She has numerous peer reviewed scientific publications, book chapters and lectures nationally and internationally.
Our phase II PENTO trial would follow a randomized, double-blind, placebo controlled, multi-center design. A stratified permuted- block randomization will be used to allocate patients to treatment. Allocations will be balanced by stage and type of drug exposed to. We recognize numerous medications have been linked to cause MRONJ and there are many newly proposed, non-operative treatments for MRONJ. However, our group will only study bisphosphonates and RANK-L inhibitor medications and the PENTO treatment regimen. With future clinical trials we hope to continue investigating other etiologies and treatments of MRONJ.
The primary predictor variable is the therapeutic intervention (PENTO). The experimental arm will be PENTO plus standard of care (SOC) as defined by the AAOMS Position Paper on MRONJ and the control arm will be SOC with a placebo. The primary outcome variable will be bone exposure area (mm2) of the primary bone lesion. Secondary outcomes will include patient pain perception measured by a visual analogue scale, radiographic changes on orthopantomogram and MRONJ stage. Outcomes will be collected at time of inclusion and then on a three-month cycle with the patient’s treatment ending at fifty-two weeks. Masked members of the data collection team include the clinicians measuring outcomes, the study coordinator and statistician. The primary analysis of interest is the association between treatment arms and area of exposed bone in mm2. The primary analysis will be completed using a mixed-effects model. A comparison will be completed for the area of the exposed bone between the two treatment arms. To power the study an alpha of 0.05, a beta of 0.10 and an anticipated dropout rate of 30% was assumed. To detect a relative change in primary outcome ≥20%, a minimum sample of forty-four patients in each study arm is required. Our desired sample size would have fifty patients per arm.
This project is also funded by the Oral and Maxillofacial Surgery Foundation, where it won the Stephen B. Milman Research Award for best research grant.