Plain English Summary
Background and study aims
Medication-related osteonecrosis of the jaws (MRONJ) is a challenging situation in clinics. Previous studies showed that pentoxifylline (PTX) combined with tocopherol was beneficial in patients with osteoradionecrosis, due to its antioxidant and antifibrotic properties. This study aims to evaluate the effect of PTX and tocopherol in patients with MRONJ.
Who can participate?
Female Stage I MRONJ patients with osteoporosis who had developed MRONJ after tooth extractions
What does the study involve?
The test group receives the pharmacological protocol with PTX and tocopherol (2 months pre-operatively and 6 months post-operatively). The control group has sequestrectomy operations (surgical removal of necrotic bone) without any pharmacological preparation. The main outcomes are clinical healing of the mucosa after 1 month and clinical and radiographic healing of the bone lesion at 6 months.
What are the possible benefits and risks of participating?
It is expected that in osteoporosis patients with Stage I MRONJ, the proposed pharmacological treatment with PTX and tocopherol will improve mucosal and bone healing rates and minimize relapses and complications, as compared to the control group.
The drugs used in the study are safe; pentoxifylline (PTX) is a methylxanthine derivate that was originally approved by the Food and Drug Administration (FDA) to treat peripheral artery diseases and has been used to treat complications related to fibrosis for over 20 years. PTX increases vasodilation and erythrocyte flexibility and reduces blood viscosity, which leads to an improvement in peripheral blood flow and tissue oxygenation. Tocopherols are organic chemical compounds consisting of various methylated phenols with beneficial effects. Tocopherols decrease tissue fibrosis, reduce inflammation, and have antioxidant effects that protect cell membranes from lipid peroxidation by reducing the free radical damage generated during oxidative stress. PTX in combination with tocopherol has a synergistic effect and is used for the management of osteoradionecrosis, with beneficial antioxidant and antifibrotic properties. The main risk for participants receiving the pharmacological treatment is that it is ineffective, and the chance of developing relapses or worsening the disease after the intervention remains high. No other risks other than those commonly associated with surgical intervention (e.g. post-operative bleeding, pain, swelling, infection) are foreseen.
Where is the study run from?
Department of Oral Surgery and Maxillofacial Surgery, Francesco Miulli Regional Hospital, University of Bari (Bari, Italy), and Oral Med Care srl, Regional Dental Medical Centre of Oral Surgery and Maxillofacial Surgery (Bitonto, Italy).
When is the study starting and how long is it expected to run for?
June 2013 to January 2023
Who is funding the study?
Francesco Miulli Regional Hospital (Generale Regionale Francesco Miulli) (Italy)
Who is the main contact?
Dr. Gianluca Colapinto, colapinto.gianluca@virgilio.it
Prof. Massimo Del Fabbro, massimo.delfabbro@unimi.it
Study website
Contact information
Type
Principal Investigator
Contact name
Dr Gianluca Colapinto
ORCID ID
Contact details
Via Giuseppe Capaldi n 9
Bitonto
70032
Italy
+39 (0)3887913143
oralmedcaresrl@gmail.com
Type
Scientific
Contact name
Prof Massimo Del Fabbro
ORCID ID
Contact details
Department of Biomedical
Surgical and Dental Sciences
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano
Via della Commenda 10
Milano
20122
Italy
+39(0)3496451220
massimo.delfabbro@unimi.it
Additional identifiers
EudraCT/CTIS number
Nil known
IRAS number
ClinicalTrials.gov number
Nil known
Protocol/serial number
Nil known
Study information
Scientific title
Effectiveness 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.
Acronym
Study hypothesis
The aim is to verify that pharmacological treatment of preparation with pentoxifylline and tocopherol in patients affected by MRONJ and candidates for surgery, improves mucosal and bone healing rates compared to patients affected by MRONJ and candidates for surgery not undergoing pharmacological preparation.
Ethics approval(s)
Approved 13/02/2014, Institutional Review Board of the Francesco Miulli Regional Hospital (Strada Prov. 127 Acquaviva – Santeramo Km. 4, 70021, 70021 Acquaviva delle Fonti BA, ACQUAVIVA delle FONTI, 70021, Italy; +39 (0)803054111; protocollo.miulli@legalmail.it), ref: 203077-13/02/2014
Study design
Single-centre interventional randomized controlled trial
Primary study design
Other
Secondary study design
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Medication-related osteonecrosis of the jaws (MRONJ) in osteoporosis patients
Intervention
All patients are randomly divided into two groups, a test group and a control group, in a double-blind manner. The test group will receive the pharmacological preparation with pentoxifylline (600 mg x 2/day) and tocopherol (800 IU x 1/day) from 2 months before to 6 months after the surgical procedure, while the control group will directly receive the surgical procedure. The results will be evaluated and it will be verified whether the pharmacological preparation improves the results.
Intervention type
Drug
Pharmaceutical study type(s)
Not Applicable
Phase
Not Applicable
Drug/device/biological/vaccine name(s)
Pentoxifylline, tocopherol
Primary outcome measure
1. Mucosal healing measured clinically by visual inspection at 1 week, 2 weeks, 1 month, 2, 6, and 12 months after the intervention
2. Bone healing measured clinically and radiographically through cone beam computed tomography (CBCT) 6 and 12 months after the intervention
Secondary outcome measures
The following secondary outcome measures will be observed yearly from 1 year up to 8 years:
1. Stability of mucosal and bone healing measured using clinical observation of the absence of inflammatory signs and maintenance of closure without bone exposure for mucosal healing, and radiographic assessment of healthy bone with normal structure, using cone beam computed tomography (CBCT)
2. Incidences of complications, such as abscess, mucosal fistula, and phlegmon, measured throughout all the study using clinical inspection and patient's reported complaints
3. Relapses occurring when mucosal healing has occurred, but bone healing does not occur, which can lead to two scenarios:
3.1. The mucosa reopens with exposure to underlying necrotic bone
3.2. The mucosa remains closed, but a small fistula is created where it is possible to probe the underlying unhealed necrotic bone measured using clinical and radiographic evaluation
Overall study start date
01/06/2013
Overall study end date
31/01/2023
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Patients with osteoporosis and MRONJ stage I
Participant type(s)
Patient
Age group
Adult
Sex
Female
Target number of participants
202
Total final enrolment
202
Participant exclusion criteria
1. Cancer patients with metastatic bone disease
2. Other stages of MRONJ
Recruitment start date
01/08/2013
Recruitment end date
01/11/2017
Locations
Countries of recruitment
Italy
Study participating centre
Department of Oral Surgery and Maxillofacial Surgery, of the Francesco Miulli Regional Hospital, University of Bari
Strada Prov. 127 Acquaviva – Santeramo Km. 4
Acquaviva delle Fonti
70021
Italy
Study participating centre
Oral Med Care srl, Regional Dental Medical Centre of Oral Surgery and Maxillo-Facial Surgery
Via Giuseppe Capaldi n 9
Bitonto
70032
Italy
Sponsor information
Organisation
Ospedale Generale Regionale Francesco Miulli
Sponsor details
Strada Prov. 127 Acquaviva – Santeramo Km. 4
Acquaviva delle Fonti
70021
Italy
+39 (0)803054111
protocollo.miulli@legalmail.it
Sponsor type
Hospital/treatment centre
Website
ROR
Funders
Funder type
Hospital/treatment centre
Funder name
Ospedale Generale Regionale Francesco Miulli
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal
Intention to publish date
15/07/2023
Individual participant data (IPD) sharing plan
Data analysed during the current study will be available upon request from Prof Massimo Del Fabbro (massimo.delfabbro@unimi.it)
IPD sharing plan summary
Available on request
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|