The PENTO protocol in Medication-Related Osteonecrosis of the Jaw (MRONJ)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Et Universitaire De Limoges

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Stomatognathic Diseases [C07]

Trial duration

29 Feb 2024 → ongoing

Decision date (initial)

2024-10-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Limoges University Hospital

External identifiers

EU CT number

2024-518688-36-00

EudraCT number

2022-002669-13

ClinicalTrials.gov

NCT05795647

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective is to assess the proportion of healing (defined as a bone exposure area (EBA) < 5 mm) in patients receiving PENTO for osteochimionecrosis at 12 months.

Secondary objectives 4

1. To describe the evolution of the modified SOMA score over 12 months (pain, chewing, bone exposure size, trismus, radiological appearance)
2. To describe the evolution of nutritional parameters over 12 months (albuminemia, pre-albuminemia, weight and BMI)
3. To follow the evolution of EBA over 12 months
4. To evaluate the tolerance of treatment by collecting adverse events over 12 months

Conditions and MedDRA coding

medication-related osteonecrosis of the Jaw

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age greater than or equal to 18 years
2. Current or past treatment with bisphosphonates (oral or IV) and/or targeted therapies (denosumab, bevacizumab)
3. Signs and symptoms for more than 8S with confirmation that the signs and symptoms are not of dental origin
4. AAOMS Stage 2 MRONJ
5. For patients of childbearing age, effective contraception is required

Exclusion criteria 24

1. History of head or neck radiotherapy or maxilla metastases
2. Patients who have received treatment in the last 3 months (PENTO or PENTOCLO protocol)
3. Patients who have undergone surgery for their MRONJ within the last 3 months
4. Pregnant or wishing to be pregnant, breastfeeding
5. Patient under palliative care
6. Patient with hypersensitivity to pentoxifylline or other methylxantine derivative or tocopherol or to an excipient
7. History of hypersensitivity reaction to penicillins, cephalosporins, or other beta-lactams (and clindamycin or lincomycin if applicable) or excipient of amoxicillin-a. clavulanic or clindamycin
8. History of jaundice/hepatic injury related to amoxicillin/clavulanic acid
9. Patient taking oral anticoagulants, or with a history of major bleeding or bleeding disorders
10. (secondary exclusion criteria) patient who sign a consent and present at inclusion a finding of hepatic, renal failure (Cl < 30 mL/min), thrombocytopenia (Pl < 80 G/L) or arterial hypotension (SAP < 90 mmHg).
11. (secondary exclusion criteria) patient who sign a consent and present at inclusion a positive beta-HCG assay (≥ 5 IU/L)
12. Patient taking platelet aggregation inhibitor, theophylline or aminophylline
13. (secondary exclusion criteria) patient who sign a consent and present at inclusion an exposure bone area (EBA) less than 5 mm (EBA<5mm)
14. (secondary exclusion criteria) patient who sign a consent and is not receiving study treatment
15. Patient taking methotrexate, probenecid, mycophenolate mofetil, myorelaxant drugs, macrolide or streptogramin antibiotics
16. Patients with hepatic failure or renal failure (Cl < 30 mL/min)
17. Patient with hypotension (SBP < 90 mmHg)
18. Refusal to participate in the study
19. Patient participating in other interventional research that may interfere with the conduct of this research
20. Patient unable to understand the protocol
21. Patient under curatorship or guardianship
22. Patient with recent or acute infarction
23. Patient taking ciprofloxacin
24. Patient taking oral antidiabetics or insulin

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is healing as defined by an exposure bone area (EBA) less than 5 mm at 12 months. It will be expressed as the percentage of patients who achieved healing (EBA < 5 mm) at 12 months.

Secondary endpoints 4

1. Progression of the modified SOMA score over 12 months: The modified SOMA score will be assessed at patient inclusion and at follow-up visits at 1, 3, 6 and 12 months.
2. Progression of nutritional parameters over 12 months: These parameters are weight (in kg), BMI (in kg/m²), albuminemia (g/L) and pre-albuminemia (mg/L). These parameters will be assessed at patient inclusion and at follow-up visits at 1, 3, 6 and 12 months.
3. 12-month change in EBA (dimension): This endpoint will be assessed quantitatively by the D dimension of EBA, defined as the measurement of the major axis of mucosal loss. This parameter will be assessed at patient inclusion and at follow-up visits at 1, 3, 6 and 12 months. The evolution of EBA corresponds to the relative regression of D defined by (D at x months - D at inclusion)/D at inclusion.
4. All adverse events are collected via questioning and blood pressure measurement at each follow-up visit (at 1-3-6-12 months). Data collected on adverse events will cover their nature, severity (mild, moderate, severe) and causality.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Et Universitaire De Limoges

Sponsor organisation

Centre Hospitalier Et Universitaire De Limoges

Address

2 Avenue Martin Luther King

City

Limoges Cedex 1

Postcode

87042

Country

France

Scientific contact point

Organisation

Centre Hospitalier Et Universitaire De Limoges

Contact name

coordinating investigator

Public contact point

Organisation

Centre Hospitalier Et Universitaire De Limoges

Contact name

project manager

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications