Study to Determine if Hyperbaric Oxygen Therapy is Helpful for Treating Radiation Tissue Injuries

Radiation Injuries Clinical Trial

Official title:

Hyperbaric Oxygen Radiation Tissue Injury Study - Project HORTIS

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00134628
• Other study ID #: Project HORTIS
• Secondary ID: ISRCTN85456814
• Status: Terminated
• Phase: Phase 3
• First received: August 23, 2005
• Last updated: January 11, 2016
• Start date: January 2001
• Est. completion date: December 2015

Study information

• Verified date: February 2012
• Source: Baromedical Research Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The principle objective of this research is to more precisely determine the degree of benefit that hyperbaric oxygen therapy affords in the treatment of late radiation tissue injury.

The study has eight* components. Seven involve the evaluation of established radionecrosis at varying anatomic sites (mandible, larynx, skin, bladder, rectum, colon, and gyn). The eighth will investigate the potential of hyperbaric oxygen (HBO) therapy to prophylax against late radiation tissue injury.

*(One of the arms, HORTIS IV - Proctitis has been closed to further patient recruitment. This decision was based on an interim statistical analysis which generated sufficient evidence to support closing down this arm of HORTIS.)

Description:

Radiation therapy is a key component of the control and eradication of malignant disease. Adequate tumoricidal doses may, however, result in damage to surrounding healthy tissue. Therapeutic radiation injuries to non-target tissues can be divided into acute, sub-acute, and delayed complications. Acute injuries are considered a direct cellular toxicity, self-limiting, and in most cases successfully managed symptomatically. Sub-acute injuries are typically identifiable in only a few organ systems, e.g., radiation pneumonitis. These, too, are generally limited but occasionally evolve to late complications. Late changes occur several months to many years after completing radiotherapy.

The etiology of radiation's late effects to normal tissue (LENT) varies somewhat between organ systems. Its hallmark, however, is one of culminating in an obliterative endarteritis, and local hypoxia.

The incidence of LENT is related to both total radiation exposure and the length of time a patient is out from completing radiotherapy. The higher the dose, the longer the interval from exposure, the greater the risk. In many cases, resulting radionecrotic lesions seriously impair form and function, and require extensive surgical correction or repair. Such surgery is fraught with complications, hence the inclusion of a "prophylactic" hyperbaric oxygen arm. A disturbing degree of mortality further complicates the development of LENT.

Hyperbaric oxygen has been utilized in the treatment of radiation tissue injury for several decades. Most of the supportive basic science and clinical evidence stems from the management of mandibular osteoradionecrosis. More recently, the use of hyperbaric oxygen has been extended to other anatomic sites. This expanded use is based, in large part, on a presumed common underlying pathophysiology of LENT, regardless of its anatomic location. Supportive clinical evidence for these other sites is limited, however, and in need of a greater degree of scientific scrutiny.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 248
• Est. completion date: December 2015
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Endarteritis

• Hypovascularity

• Diarrhea

• Cramping

• Obstruction

• Stricture

• Pain

• Hemorrhage

• Wall Changes

• Ulceration

• Hypocellularity

• Mucosal thickening

• Vomiting

• Tenesmus

• Constipation

• Perforation

• Fistula

• Obstipation

• Tissue hypoxia

Exclusion Criteria:

• Pregnancy

• Reactive airway disease

• Radiographic evidence of pulmonary blebs or bullae

• Untreated pneumothorax

• Previously documented ejection fraction less than 35%

• History of seizures except childhood febrile seizures

• Cardiovascular instability

• Mechanical ventilator support with the exception of those patients who are immediately (1-5 days) post-operative

• Unable to follow simple commands

• Not orientated to person, place, time

• Participating as a subject in any other medical or biomedical research project; if previously involved as a subject, sufficient time must have elapsed to permit "wash out" of any investigational agent.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Radiation Injuries

Intervention

Procedure:
• Hyperbaric Oxygen Therapy
HBO at 2.0 ATA
• Sham treatment
Normal air under pressure (1.1 ATA)

Locations

Country	Name	City	State
Australia	Wesley Medical Center	Brisbane	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Mexico	Instituto Nacional de Cancerologica	Mexico City
South Africa	University of Stellenbosch	Cape Town
South Africa	University of Pretoria Medical Center	Pretoria
Turkey	Istanbul University Medical Center	Istanbul
United States	Palmetto Health Richland	Columbia	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Baromedical Research Foundation

Countries where clinical trial is conducted

United States,  Australia,  Mexico,  South Africa,  Turkey, 

References & Publications (10)

Bevers RF, Bakker DJ, Kurth KH. Hyperbaric oxygen treatment for haemorrhagic radiation cystitis. Lancet. 1995 Sep 23;346(8978):803-5. — View Citation

Curi MM, Dib LL. Osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg. 1997 Jun;55(6):540-4; discussion 545-6. — View Citation

Feldmeier JJ, Heimbach RD, Davolt DA, Brakora MJ. Hyperbaric oxygen as an adjunctive treatment for severe laryngeal necrosis: a report of nine consecutive cases. Undersea Hyperb Med. 1993 Dec;20(4):329-35. — View Citation

Hart GB, Mainous EG. The treatment of radiation necrosis with hyperbaric oxygen (OHP). Cancer. 1976 Jun;37(6):2580-5. — View Citation

Joseph DL, Shumrick DL. Risks of head and neck surgery in previously irradiated patients. Arch Otolaryngol. 1973 May;97(5):381-4. — View Citation

Marx RE. A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg. 1983 Jun;41(6):351-7. — View Citation

Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg. 1983 May;41(5):283-8. — View Citation

Samuels L, Granick MS, Ramasastry S, Solomon MP, Hurwitz D. Reconstruction of radiation-induced chest wall lesions. Ann Plast Surg. 1993 Nov;31(5):399-405. — View Citation

Williams JA Jr, Clarke D, Dennis WA, Dennis EJ 3rd, Smith ST. The treatment of pelvic soft tissue radiation necrosis with hyperbaric oxygen. Am J Obstet Gynecol. 1992 Aug;167(2):412-5; discussion 415-6. — View Citation

Woo TC, Joseph D, Oxer H. Hyperbaric oxygen treatment for radiation proctitis. Int J Radiat Oncol Biol Phys. 1997 Jun 1;38(3):619-22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SOMA (Subjective, Objective, Management, Analytic) scale used to determine late effects to normal tissue (LENT) score		pre-treatment, post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years	No
Secondary	Clinical assessment using one of the following criteria:		post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years	No
Secondary	Healed		post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years	No
Secondary	Modestly improved (< 50% lesion resolution)		post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years	No
Secondary	Not improved		post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years	No
Secondary	Other (e.g. lesion recurrence, lesion size progression)		post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years	No
Secondary	Significant Improvement (>50% lesion resolution)		post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years	No

External Links

•   Research activities undertaken by the Baromedical Research Foundation