Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04934644 |
| Other study ID # |
ORN |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 19, 2019 |
| Est. completion date |
March 19, 2024 |
Study information
| Verified date |
June 2021 |
| Source |
Göteborg University |
| Contact |
Louise Sameby, MD |
| Phone |
+46313436713 |
| Email |
louise.sameby[@]vgregion.se |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Osteoradionecrosis (ORN) is a severe delayed radiation-induced injury that can occur in
patients whom have been subjected to radiotherapy for head and neck cancer. Hyperbaric oxygen
treatment (HBO) is one treatment option. In Sweden it is used in some locations in
combination to standard treatment which includes for example antibiotics, pain medication and
surgery. There is still not sufficient evidence that this treatment is effective in this
group of patients.
The primary aim of this study will be to evaluate HBO as a treatment for osteoradionecrosis
in terms of slowing the progression of the disease, or at the best, cure the disease.
Description:
Radiotherapy (RT) is frequently used for treatment of head and neck cancer, in combination
with surgery and chemotherapy. Although RT can improve the survival rate among head and
neck-cancer patients, it has negative effects on the healthy tissue surrounding the tumour.
Osteoradionecrosis (ORN) is a severe delayed radiation-induced injury that can occur in
patients whom have been subjected to RT for head and neck cancer. ORN can occur within months
to several years after radiotherapy. Symptoms can include pain, dysesthesia, halitosis (bad
breath) exposed necrotic bone, infection, orocutaneous fistula and pathologic fractures. The
mandible is the most common site affected by ORN, but other bones can be affected as well.
ORN has earlier been treated with long-term antibiotics and surgery. Today the treatment is
multidisciplinary and also includes local wound care, hyperbaric oxygen (HBO) and new
medications for example Pentoxifylline, a vasodilator that also inhibits fibrosis, Tocopherol
(Vitamin E), that reduces damage by free radicals, and Clodronate, a bisphosphonate that
inhibits bone resorption.
Hyperbaric oxygen treatment (HBO) is an intervention in which the individual breathes near
100% oxygen intermittently while inside a hyperbaric chamber that is pressurized to above sea
level pressure. By increasing the inspired partial pressure of oxygen (PO₂), with an
increased O₂ fraction inspired and increased pressure, the amount of oxygen in blood can be
increased. This also increases the distance that oxygen can diffuse from the capillaries into
the tissues. HBO increase production of reactive oxygen and nitrogen species. This leads to
neovascularisation by two processes: blood vessel growth by local endothelial cells
(angiogenesis) and recruitment and differentiation of stem cells to form vessels "de novo"
(vasculogenesis). HBO has also been shown to stimulate fibroblast proliferation and enhances
collagen synthesis.
The primary aim of this study will be to evaluate HBO as a treatment for osteoradionecrosis
in terms of slowing the progression of the disease, or at the best, cure the disease. As
secondary aims for this study, the effect of HBO on pain, infection, mouth-opening capacity
and quality of life will be evaluated.
The study will be a prospective study with matched controls evaluating the effect of HBO in
comparison to standard care in patients with ORN stage 1-2b according to classification of
Kagan and Schwartz. A total of 60 patients in each group will be included, which should be
sufficient for statistical significance according to power calculations.
The patients will be enrolled into two groups. The first group of patients will receive HBO
treatment. The treatment will be given in a multi or monoplace chamber pressurized to 2,4-2,5
ATA, 90 minutes from start to decompression, and the patients will be breathing 100 % oxygen.
Treatment will be given once daily, five days a week. All patients will receive 30 treatments
and if surgery is needed the patient will receive an additional 10 treatments
postoperatively. All according to local routines for treatment of ORN with HBO. The control
group will consist of a group of patients with the same diagnosis and same stage of ORN.
These will be patients from a maxillofacial unit in Sweden not using HBO treatment or
patients who decline the treatment. The controls will be matched based on sex, age,
tumour-stage and RT. These patients will be treated with standard care and be subjected to
surgery if needed.
Baseline visit will include clinical examination by an oral and maxillofacial surgeon and
quality of life questionnaires developed and validated for head-and-neck cancer patients
(EORTC QLQ C30 and H&N35). The patients in the HBO group will also be examined by a doctor at
the hyperbaric unit. Follow-up will be performed every third month during the first year. In
total the patients will be followed for a period of four years, every sixth months the second
and third year and then on a yearly basis from the third year and on if no need for more
frequent controls exist. The follow-up will include clinical examination by an oral and
maxillofacial surgeon, radiographies including CT-scan and quality of life questionnaires.
This is according to established care program. Blood samples, and if the patient undergoes
surgery, tissue samples, will also be collected to look at biomarkers for inflammation and
bone turnover.
Primary end-point of the study is changes in the bone as well as the soft tissue surrounding
the necrotic bone. Secondary end-points are improvements regarding pain, infection,
mouth-opening capacity and quality of life scorings.
