Radiation InjuriesPhase 3NCT00134628
Study to Determine if Hyperbaric Oxygen Therapy is Helpful for Treating Radiation Tissue Injuries
A Phase 3 study testing Hyperbaric Oxygen Therapy in people with Radiation Injuries, run by National Baromedical Services at 7 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Radiation Injuries
- What is being tested?
- Hyperbaric Oxygen Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 248 participants
- Where
- 7 sitesin 5 countries
- Study dates
- Jan 2001to Dec 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Endarteritis
- Hypovascularity
- Diarrhea
- Cramping
- Obstruction
- Stricture
Show all 19Show fewer
- Pain
- Hemorrhage
- Wall Changes
- Ulceration
- Hypocellularity
- Mucosal thickening
- Vomiting
- Tenesmus
- Constipation
- Perforation
- Fistula
- Obstipation
- Tissue hypoxia
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
Australia2 sites
Wesley Medical Center
Brisbane, Queensland, 4064
Royal Hobart Hospital
Hobart, Tasmania, 7001
South Africa2 sites
University of Stellenbosch
Cape Town
University of Pretoria Medical Center
Pretoria, 0001
United States1 site
Palmetto Health Richland
Columbia, South Carolina, 29203
Turkey (Türkiye)1 site
Istanbul University Medical Center
Istanbul, 34390
About this study
Official title: Hyperbaric Oxygen Radiation Tissue Injury Study - Project HORTIS
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.)
Read the detailed 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.
- Conditions
- Radiation Injuries
- Being tested
- Hyperbaric Oxygen Therapy, Sham treatment
- Keywords
- Hyperbaric Oxygenation, Radiation injuries, Prophylaxis, Proctitis, Cystitis, Enteritis, Osteoradionecrosis
- Medical subject headings
- Radiation Injuries, Proctitis, Cystitis, Enteritis, Osteoradionecrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperbaric Oxygen TherapyProcedure or surgery
HBO at 2.0 ATA
Sham treatmentProcedure or surgery
Normal air under pressure (1.1 ATA)
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Hyperbaric Oxygen Therapy Receives: Procedure: Hyperbaric Oxygen Therapy |
| B | Sham comparator | Normal Air Receives: Procedure: Sham treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
SOMA (Subjective, Objective, Management, Analytic) scale used to determine late effects to normal tissue (LENT) score
Measured: pre-treatment, post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Secondary outcomes (6)
Clinical assessment using one of the following criteria:
Measured: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Healed
Measured: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Modestly improved (< 50% lesion resolution)
Measured: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Not improved
Measured: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Other (e.g. lesion recurrence, lesion size progression)
Measured: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Significant Improvement (>50% lesion resolution)
Measured: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2005 (estimated)
- Study startJan 2001
- Primary completionAug 2011
- Study completionDec 2015
Why it stopped: Discontinued cystitis study due to poor recruitment. To continue the trial under these circumstances is considered non-viable.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Radiation InjuriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 248 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Baromedical Services
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dick Clarke, National Baromedical Services
- Investigators
- Dick Clarke, CHT, Principal investigator, National Baromedical Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00134628
- Sponsor's protocol ID
- Project HORTIS
- Other IDs
- ISRCTN85456814
- Status last verified
- Feb 2012
- First submitted
- 23 Aug 2005
- Last updated
- 12 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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. doi: 10.1016/s0278-2391(97)90478-x.
PubMed 9191633Joseph DL, Shumrick DL. Risks of head and neck surgery in previously irradiated patients. Arch Otolaryngol. 1973 May;97(5):381-4. doi: 10.1001/archotol.1973.00780010393005. No abstract available.
PubMed 4703530Samuels 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. doi: 10.1097/00000637-199311000-00003.
PubMed 8285524Hart GB, Mainous EG. The treatment of radiation necrosis with hyperbaric oxygen (OHP). Cancer. 1976 Jun;37(6):2580-5. doi: 10.1002/1097-0142(197606)37:63.0.co;2-h.
PubMed 949677Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg. 1983 May;41(5):283-8. doi: 10.1016/0278-2391(83)90294-x.
PubMed 6572704Marx RE. A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg. 1983 Jun;41(6):351-7. doi: 10.1016/s0278-2391(83)80005-6. No abstract available.
PubMed 6574217Bevers RF, Bakker DJ, Kurth KH. Hyperbaric oxygen treatment for haemorrhagic radiation cystitis. Lancet. 1995 Sep 23;346(8978):803-5. doi: 10.1016/s0140-6736(95)91620-2.
PubMed 7674746Woo TC, Joseph D, Oxer H. Hyperbaric oxygen treatment for radiation proctitis. Int J Radiat Oncol Biol Phys. 1997 Jun 1;38(3):619-22. doi: 10.1016/s0360-3016(97)00017-5.
PubMed 9231688Williams 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. doi: 10.1016/s0002-9378(11)91421-5.
PubMed 1497044Feldmeier 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.
PubMed 8286987
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperbaric Oxygen Radiation Tissue Injury Study - Project HORTIS
- ClinicalTrials.gov ID
- NCT00134628
- Acronym / sponsor ID
- Project HORTIS
- Conditions
- Radiation Injuries
- Keywords
- Hyperbaric Oxygenation, Radiation injuries, Prophylaxis, Proctitis, Cystitis, Enteritis, Osteoradionecrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Discontinued cystitis study due to poor recruitment. To continue the trial under these circumstances is considered non-viable.
- Enrolment
- 248 participants (actual)
- Lead sponsor
- National Baromedical ServicesUniversity, hospital or other
- Study start
- Jan 2001
- Primary completion
- Aug 2011 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 25 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.)
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Procedure: Hyperbaric Oxygen TherapyHyperbaric Oxygen Therapy |
| B | Sham comparator | Procedure: Sham treatmentNormal Air |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Endarteritis
- Hypovascularity
- Diarrhea
- Cramping
- Obstruction
Key exclusion criteria (11 listed)
- Pregnancy
- Reactive airway disease
- Radiographic evidence of pulmonary blebs or bullae
- Untreated pneumothorax
- Previously documented ejection fraction less than 35%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperbaric Oxygen TherapyHBO at 2.0 ATA | Procedure or surgery | A |
| Sham treatmentNormal air under pressure (1.1 ATA) | Procedure or surgery | B |
Primary outcome
SOMA (Subjective, Objective, Management, Analytic) scale used to determine late effects to normal tissue (LENT) score
Time frame: pre-treatment, post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
6 secondary outcomes
Clinical assessment using one of the following criteria:
Time frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Healed
Time frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Modestly improved (< 50% lesion resolution)
Time frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Not improved
Time frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Other (e.g. lesion recurrence, lesion size progression)
Time frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Significant Improvement (>50% lesion resolution)
Time frame: post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years
Results and safety
The study was stopped early (reason given: Discontinued cystitis study due to poor recruitment. To continue the trial under these circumstances is considered non-viable.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2016.
- Background: PubMed 9191633Curi 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. doi: 10.1016/s0278-2391(97)90478-x.
- Background: PubMed 4703530Joseph DL, Shumrick DL. Risks of head and neck surgery in previously irradiated patients. Arch Otolaryngol. 1973 May;97(5):381-4. doi: 10.1001/archotol.1973.00780010393005. No abstract available.
- Background: PubMed 8285524Samuels 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. doi: 10.1097/00000637-199311000-00003.
- Background: PubMed 949677Hart GB, Mainous EG. The treatment of radiation necrosis with hyperbaric oxygen (OHP). Cancer. 1976 Jun;37(6):2580-5. doi: 10.1002/1097-0142(197606)37:63.0.co;2-h.
- Background: PubMed 6572704Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg. 1983 May;41(5):283-8. doi: 10.1016/0278-2391(83)90294-x.
- Background: PubMed 6574217Marx RE. A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg. 1983 Jun;41(6):351-7. doi: 10.1016/s0278-2391(83)80005-6. No abstract available.
- Background: PubMed 7674746Bevers RF, Bakker DJ, Kurth KH. Hyperbaric oxygen treatment for haemorrhagic radiation cystitis. Lancet. 1995 Sep 23;346(8978):803-5. doi: 10.1016/s0140-6736(95)91620-2.
- Background: PubMed 9231688Woo TC, Joseph D, Oxer H. Hyperbaric oxygen treatment for radiation proctitis. Int J Radiat Oncol Biol Phys. 1997 Jun 1;38(3):619-22. doi: 10.1016/s0360-3016(97)00017-5.
- Background: PubMed 1497044Williams 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. doi: 10.1016/s0002-9378(11)91421-5.
- Background: PubMed 8286987Feldmeier 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dick Clarke, CHT principal investigator
National Baromedical Services
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hyperbaric Oxygen Therapy in people with Radiation Injuries, run by National Baromedical Services at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia, South Africa, United States, Mexico, Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Discontinued cystitis study due to poor recruitment. To continue the trial under these circumstances is considered non-viable.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SOMA (Subjective, Objective, Management, Analytic) scale used to determine late effects to normal tissue (LENT) score (time frame: pre-treatment, post-treatment (HBO and placebo) and at follow ups at 3 months, 6 months, and 1 year through 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00134628, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2016.