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Trial registered on ANZCTR


Registration number
ACTRN12607000559415
Ethics application status
Approved
Date submitted
24/10/2007
Date registered
31/10/2007
Date last updated
25/10/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Hyperbaric Oxygen in Lower Limb Trauma
Scientific title
In open tibial fractures with severe soft tissue injury, does an early course of hyperbaric oxygen, when compared with standard trauma care, reduce acute soft tissue complication rates and improve short and long term outcomes?
Secondary ID [1] 485 0
ClinicalTrials.gov - NCT00264511
Universal Trial Number (UTN)
Trial acronym
HOLLT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Trauma 2262 0
Fracture 2263 0
Outcomes 2264 0
Complications of Injury 2265 0
Acute open fractures of the tibia with associated severe soft tissue injury 2499 0
Condition category
Condition code
Injuries and Accidents 2355 2355 0 0
Fractures
Musculoskeletal 2595 2595 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A course of 12 hyperbaric oxygen (HBO) therapy sessions over approximately 8 days, commencing within 48 hours of injury. HBO treatment will be provided at 2.4 atmospheres absolute (ATA) pressure for approximately 90 minutes of oxygen therapy. Treatments should be twice daily for the first three days. Patient follow up will continue for 2 years.
Intervention code [1] 2225 0
Treatment: Other
Comparator / control treatment
No hyperbaric treatment. Control patients will receive Standard Care, that is, normal trauma care as practiced at the admitting hospital
Control group
Active

Outcomes
Primary outcome [1] 3252 0
Significant soft tissue necrosis
Timepoint [1] 3252 0
After initial surgery and up to 14 days
Primary outcome [2] 3253 0
Wound infection
Timepoint [2] 3253 0
Within 14 days after randomisation
Primary outcome [3] 3506 0
Soft tissue complication rate
Timepoint [3] 3506 0
14 days post injury
Secondary outcome [1] 5416 0
Time to radiological union
Timepoint [1] 5416 0
6 weeks, 3, 6, 9, 12, 18, 24 months
Secondary outcome [2] 5417 0
Amputation
Timepoint [2] 5417 0
Within initial hospital admission after randomisation
Secondary outcome [3] 5418 0
Time until wound closure
Timepoint [3] 5418 0
Within initial hospital admission after randomisation
Secondary outcome [4] 5419 0
Breakdown of closed wounds
Timepoint [4] 5419 0
Within initial hospital admission after randomisation
Secondary outcome [5] 5420 0
Number of operative procedures
Timepoint [5] 5420 0
Within initial hospital admission after randomisation
Secondary outcome [6] 5421 0
length of stay in intensive care unit
Timepoint [6] 5421 0
Within initial hospital admission after randomisation
Secondary outcome [7] 5422 0
length of stay in the acute hospital
Timepoint [7] 5422 0
Within initial hospital admission after randomisation
Secondary outcome [8] 5423 0
Soft tissue infection
Timepoint [8] 5423 0
At 3, 6, 9, 12, 18 & 24 month Follow-up
Secondary outcome [9] 5424 0
Osteomyelitis
Timepoint [9] 5424 0
At 3, 6, 9, 12, 18 & 24 month Follow-up
Secondary outcome [10] 5425 0
Other wound complications
Timepoint [10] 5425 0
At 3, 6, 9, 12, 18 & 24 month Follow-up
Secondary outcome [11] 5426 0
If patient is able to weight bear
Timepoint [11] 5426 0
At 3, 6, 9, 12, 18 & 24 month Follow-up
Secondary outcome [12] 5427 0
Bone graft
Timepoint [12] 5427 0
At 3, 6, 9, 12, 18 & 24 month Follow-up
Secondary outcome [13] 5428 0
Any other late surgical procedures
Timepoint [13] 5428 0
At 3, 6, 9, 12, 18 & 24 month Follow-up
Secondary outcome [14] 5436 0
Time until definitive orthopaedic fixation
Timepoint [14] 5436 0
Within initial hospital admission after randomisation
Secondary outcome [15] 5855 0
Functional state and quality of life
Timepoint [15] 5855 0
12 months and 2 years

Eligibility
Key inclusion criteria
* Subjects will have suffered an acute open fracture of the tibia with severe soft tissue injury and a high risk of injury related complications as judged by an assessment of the injury, the injury mechanism(s) and the host status (generally aimed to identify Gustilo Grade 3 injury). Digital photography and radiology will be used as an audit tool and to confirm subtypes of severity grading.
* Minimum age 18 years (or older where collaborators local consent procedures require this)
* Enrolment within 48 hours of injury with expectation of commencement of HBO therapy within 48 hours of injury. Note: subject can remain in study if HBO unexpectedly delayed after enrolment
* Permission to enrol of patient granted by trauma team managing patient
* Consent from patient or next of kin
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Other injuries, instability or resuscitation / intensive care requirements judged by the trauma surgeon or intensive care specialist to be incompatible with safe hyperbaric oxygen therapy

* Malignancy, renal failure, diabetes, cardiac failure or other serious medical condition where the severity of the condition is such that the patient is not expected to survive for the follow up period or where it is likely that there will be significant health deterioration within the two years of follow up.

* Significant peripheral vascular disease or other limb problems which themselves would be expected to interfere with longevity or outcomes of the limb over the follow up period.

* Contraindications to hyperbaric therapy including pregnancy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Log on to a secure web server to register subject and obtain enrolment number and allocation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomization tables on site by site basis to minimise likelihood significant variations in allocation at each site
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
International, multi-centre study. Initial hyperbaric oxygen within 48 hours and 12 sessions in total. Initial surgery masked. Main outcome measures scored by blinded observers at Monash University
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 376 0
3004
Recruitment postcode(s) [2] 3046 0
7000
Recruitment outside Australia
Country [1] 461 0
Italy
State/province [1] 461 0
Rome
Country [2] 462 0
Czech Republic
State/province [2] 462 0
Pilsen
Country [3] 463 0
Sweden
State/province [3] 463 0
Stockholm
Country [4] 464 0
Norway
State/province [4] 464 0
Oslo
Country [5] 465 0
South Africa
State/province [5] 465 0
Cape Town
Country [6] 466 0
Czech Republic
State/province [6] 466 0
Ostrava
Country [7] 467 0
Austria
State/province [7] 467 0
Graz
Country [8] 468 0
Portugal
State/province [8] 468 0
Matosinhos
Country [9] 469 0
India
State/province [9] 469 0
New Delhi
Country [10] 6317 0
United States of America
State/province [10] 6317 0
Walnut Creek, California
Country [11] 6318 0
Chile
State/province [11] 6318 0
Santiago

Funding & Sponsors
Funding source category [1] 2511 0
Government body
Name [1] 2511 0
Transport Accident Commission
Address [1] 2511 0
Level 6, 60 Brougham Street, Geelong, VIC 3220
Country [1] 2511 0
Australia
Funding source category [2] 2745 0
Government body
Name [2] 2745 0
NHMRC Project Grant 2008-2012
Address [2] 2745 0
Level 5, 20 Allara Street
Canberra ACT 2601
Country [2] 2745 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
The Alfred
P.O Box 315
Prahran. Vic. 3181.
Country
Australia
Secondary sponsor category [1] 2480 0
Hospital
Name [1] 2480 0
Various collaborating hospitals worldwide
Address [1] 2480 0
Melbourne, Stockholm, Pilsen, Graz, Rome, Ostrava, Oslo - others being sought
Country [1] 2480 0
Sweden

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4427 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 4427 0
Commercial Road
Melbourne, 3004
Ethics committee country [1] 4427 0
Australia
Date submitted for ethics approval [1] 4427 0
Approval date [1] 4427 0
15/11/2004
Ethics approval number [1] 4427 0
206/04
Ethics committee name [2] 4664 0
Monash University Human Research Ethics Committee
Ethics committee address [2] 4664 0
Monash University, VIC 3800
Ethics committee country [2] 4664 0
Australia
Date submitted for ethics approval [2] 4664 0
Approval date [2] 4664 0
19/12/2006
Ethics approval number [2] 4664 0
2006/993MC

Summary
Brief summary
Hyperbaric oxygen therapy may reduce injury related complications and improve outcomes following serious musculo-skeletal injury. The Hyperbaric Oxygen in Lower Limb Trauma (HOLLT) Study will investigate this by conducting a randomised controlled trial aiming to enrol 120 patients with severe tibial fractures within 48 hours of their injury. The study is being conducted by an international network of trauma centres with hyperbaric treatment facilities.
Trial website
https://www.hollt.org/Application/home.aspx
Trial related presentations / publications
* No Publications to date.
Note that the HOLLT study has been referenced in the new European Textbook of Hyperbaric Medicine

* Presentations:
Millar I, Williamson O, Cameron P, Myles P; Hyperbaric Oxygen in Lower Limb Trauma (HOLLT): Designing a randomised multi-centre study. Poster and Presentation, June 2007, Undersea and Hyperbaric Medical Society Annual Scientific Meeting, Hawaii,
Public notes

Contacts
Principal investigator
Name 27478 0
Dr Ian Millar
Address 27478 0
Hyperbaric Service The Alfred Hospital, PO BOX 315, Melbourne, Victoria, 3004
Country 27478 0
Australia
Phone 27478 0
+61 3 9076 2269
Fax 27478 0
Email 27478 0
i.millar@alfred.org.au
Contact person for public queries
Name 10733 0
Dr Rosemary McGinnes (Project Coordinator)
Address 10733 0
Department of Epidemiology & Preventive Medicine (DEPM)
Monash University, Alfred Hospital
Commercial Road
Melbourne, VIC, 3004
Australia
Country 10733 0
Australia
Phone 10733 0
+61 (0)3 9903 0926
Fax 10733 0
+61 (0)3 9076 3052
Email 10733 0
hollt@monash.edu
Contact person for scientific queries
Name 1661 0
Dr Ian Millar
Address 1661 0
Hyperbaric Service
The Alfred Hospital
PO BOX 315
Melbourne, Victoria, 3004
Country 1661 0
Australia
Phone 1661 0
+61 3 9076 2269
Fax 1661 0
+61 3 9076 3052
Email 1661 0
i.millar@alfred.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary