Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT00127725 |
| Other study ID # |
05/023 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
August 5, 2005 |
| Last updated |
November 14, 2005 |
| Start date |
August 2005 |
| Est. completion date |
August 2009 |
Study information
| Verified date |
August 2005 |
| Source |
Sydney South West Area Health Service |
| Contact |
Ian A Harris, MBBS |
| Phone |
+ 61 2 8777 5228 |
| Email |
ian.harris[@]swsahs.nsw.gov.au |
| Is FDA regulated |
No |
| Health authority |
Australia: Department of Health and Ageing Therapeutic Goods Administration |
| Study type |
Interventional
|
Clinical Trial Summary
Fractures of the tibial shaft (diaphysis) are some of the most common long bone fractures.
They most frequently occur in males less than 40 years of age. Despite advancements in the
surgical management of these fractures, the precarious blood supply and lack of soft-tissue
cover of the shaft of the tibia make these fractures vulnerable to non-union and infection.
These complications often require multiple procedures, extended time off of work, and can
result in ongoing poor mobility. This is reflected in the surgical revision rate that the
scientific literature has recorded as being between 20 and 30%.
Pulsed electromagnetic field (PEMF) stimulation has been shown to be a safe and effective
treatment for non-unions of the tibia. These are fractures in which the bone has failed to
unite and the healing process has ceased. The PEMF is delivered via a device such as the EBI
Bone Healing System®, which straps onto the limb overlying the fracture. It is lightweight
and portable using a rechargeable battery for power. It is compatible with internal and
external fixation and may also be worn over a plaster or fibreglass cast. It is usually kept
in place for ten hours per day and used for a period of three months or until the fracture
unites. In animal models, PEMF stimulation has been demonstrated to improve the time to
fracture healing in acute fractures. There have been no demonstrated side effects of the
therapy.
The study hypothesis is that PEMF stimulation during the first twelve weeks after fracture,
in addition to normal surgical care, will increase the union rate for these fractures and
thereby significantly reduce the surgical revision rate within the first twelve months
following fracture.
Description:
Study Objectives:
This is a randomized controlled study whose objective is to determine whether PEMF
stimulation as an adjunct therapy has a clinically significant effect on the morbidity
associated with tibial shaft fractures.
It is a two-armed study. The active treatment arm involves participants with acute tibial
shaft fractures who have been randomized to receive a PEMF stimulation device to be worn
over the fracture site for 10 hours per day during the first twelve weeks after injury. The
control arm involves participants with acute tibial shaft fractures who have been randomized
to receive a placebo device to be worn over the fracture site for 10 hours per day during
the first twelve weeks after injury.
Primary Aim:
- To determine whether the use of a PEMF stimulation device as adjunct therapy for acute
tibial shaft fractures reduces the surgical revision rate in the 12 months after
injury.
Revision surgery for the purposes of this study is defined as any surgery on the injured leg
(between the knee joint and ankle joint) more than 14 days after the accident, except
operations designed to provide initial skin coverage or skin closure, or the removal of an
external fixateur as an isolated procedure. Revision surgery will be classified as minor or
major. Minor revision will be defined as dynamisation of an intramedullary nail through the
percutaneous removal of a static locking screw. Major revision surgery will include all
other revision surgery as defined above. Major revision surgery will be sub-classified as
procedures involving either bone grafting, and/or revision of fixation, and/or for the
treatment of established infection, or amputation, and the rates will be compared across
treatment and placebo arms.
Secondary Aims:
- To determine whether the use of a PEMF stimulation device as adjunct therapy for acute
tibial shaft fractures increases the radiological and clinical union rates at 12, 26
and 52 weeks after injury. A fracture will be deemed to have radiologically united at
these times if by independent observation, two orthopaedic consultants agree that three
bony cortices are bridged by bony callus on an anteroposterior and lateral plain X-ray
at these times. If the two reviewers disagree, a third opinion will be sought which
will be final. A fracture will be deemed to have clinically united if it is deemed
stable under clinical examination by the treating orthopaedic surgeon at these times.
- To determine whether the use of a PEMF stimulation device as adjunct therapy for acute
tibial shaft fractures increases the patients' general health score, as measured by the
SF-36 general health survey; and function of the injured limb, as measured by the Lower
Extremity Functional Scale at 12, 26 and 52 weeks after injury.
Primary Hypothesis:
- That there will be significantly lower rates of surgical revision within 12 months of
injury in those participants who received active PEMF stimulation for the first 12
weeks after injury.
Secondary Hypotheses:
- That there will be increased union rates at 12, 26 and 52 weeks after fracture among
participants who received active stimulation.
- That the average score on a general health survey and region specific health survey
will be higher among participants who received active stimulation.
Research Plan
Study Population:
All adults (18 years and over) with diaphyseal fractures of the tibia who present to a
recruiting hospital during the study period will be eligible to enrol into the study. The AO
classification 42 will be used to define tibial shaft fractures. Any fracture that extends
into the articular surface will be excluded. From an analysis of previous Liverpool patients
and the literature, the investigators expect that this population will be 75% - 85% male
with an average age of 30-35 years old. There will be no upper limit to ages. If a
participant has sustained bilateral tibial shaft fractures, each will be enrolled
separately, left before right.
Eligible patients will be approached by a senior member of their treating team, either
registrar or consultant, and given an information sheet to read and have the opportunity to
have any questions answered. They will then be asked to sign a consent form if they would
like to participate in the study. Interpreters will be used during this process for
non-english speaking patients.
There will be a 14-day window period post injury in which the device must be applied for the
patient to enter the study. If there is any reason why the device cannot be applied by this
time, the patient will be excluded from the study. The most commonly encountered reason the
investigators expect for this will be a patient who remains in an Intensive Care Unit over
14 days, where electrically sensitive equipment is being used for patient care.
Patients with pacemakers or defibrillators will be excluded, as PEMF stimulation may affect
some types of these devices. Patients with pathological fractures due to malignant tumours
will be excluded. Pregnant patients will be excluded, as the device is yet to be studied in
pregnancy. Patients without the cognitive ability to consent are excluded.
The recruiting hospitals are Liverpool Hospital, St. George Hospital, Westmead Hospital,
Nepean Hospital and Wollongong Hospital. Approval has been granted for the study to commence
through each hospital’s Human Research Ethics Committee. Recruitment of patients will
commence on Monday August 14, 2005, at each of these hospitals. Recruitment will end after
the target of 340 participants has been enrolled into the study.
Baseline Measures:
Participants will be asked to complete a brief questionnaire on enrolment to determine
potential risk factors for non-union. These data will be that of age, smoking, general
medical conditions and medications used. The participants’ current occupation will also be
sought as this may effect the time taken for return to work.
The treating doctor will be asked to complete a questionnaire on other risk factors. This
will include details of the mechanism of injury, whether the injury was open or closed (and
the Gustillo grade of an open injury), other injuries the participant has sustained, and the
treatment received for their injuries, as well as the patients' insurance status. The
definitive treatment for the tibia fracture will be classified as either external fixation
with casts (plater of paris or fibreglass), intramedullary nailing, internal fixation with
plates and screws, or external fixation.
Copies of the initial X-rays will be collected. The fractures will be classified into the
nine fracture patterns as defined under the AO classification system by a panel of three
orthopaedic consultants experienced in trauma.
Randomisation Process:
After the consent form has been signed and the baseline data collected, the participants
will be assigned to either active or inactive arms by the NH&MRC Clinical Trials Centre
(CTC) located at Sydney University. Devices will come from a pool of seventy devices, which
have been supplied by BiometÒ Australia and are commercially known as the EBI Bone Healing
System®. Thirty-five of these devices will be active and thirty-five inactive, and they will
be randomly numbered from 1 to 70 by the CTC. The CTC will have the code for active and
inactive devices and will conduct the randomisation process using the statistical technique
of minimisation, a dynamic allocation process designed to balance known risk factors across
treatment arms. The two factors that will be minimised for are the recruiting hospital and
whether the injury was closed or open. A device will then be randomly assigned from the
available pool of either active or inactive devices, and this assigned device will then be
fitted to the patient. The researchers, company representatives, surgeons and patients will
all remain blinded to active/inactive arms until all the data have been collected and
analysed.
Interventions:
Enrolment in the study will not affect any other aspect of the participants' care. All
participants will undergo the normal surgical intervention and follow up for their tibial
shaft fracture and any other injuries as recommended by their treating surgeons.
After a participant has been assigned with a device number, sales representatives of BiometÒ
Australia will fit them with it within three working days, in either the hospital ward or
the participant’s home. Participants will receive instructions on how to use the device, and
be required to wear the device for ten hours per day for a period of twelve weeks. The
devices are manufactured to record the amount of time in which they have been used and
thereby measure compliance. Non-compliance will be defined as average use of less than six
hours per day. Participants will also be asked at twelve weeks about their average use of
the device.
After twelve weeks the research team or company representatives will collect the devices,
replace the straps, clean and check them before they re-enter the pool of devices for
assignment.
Data Collection:
Data will be collected at 12, 26, and 52 weeks from both participants and their treating
surgeons. Participants will receive a survey in the mail, and then be contacted over the
phone to attain their answers. On each occasion they will be asked whether they have had any
further procedures on their leg, and if so at which hospital and by whom. At three months
they will also be asked about their average use of the device, whether they are seeing their
surgeon in private rooms or a hospital clinic and of their insurance status. That is, are
they being treated under medicare, private health insurance, workers compensation, or third
party insurance. They will be asked if they have managed to return to work, and to complete
the Lower Extremity Functional Score as well as the Short Form-36 (a general health survey).
The phone questionnaire is expected to take 15-30 minutes each time.
Their surgeons will also be contacted at 12, 26 and 52 weeks to determine if there has been
any further surgery or other complications, and to gain their opinion on fracture union.
Copies of their routine pre-operative and twelve week X-rays will be collected for review.
Preoperative X-rays will be classified according to the AO classification system into the 9
sub classifications of tibial shaft fractures by a panel of three orthopaedic surgeons. Two
orthopaedic surgeons experienced in trauma, who will remain blinded to the treatment arm of
the patients, will assess the twelve-week X-rays to determine if union has occurred.
Fracture union rates at twelve weeks will be quantified. Fracture union will be defined as
mature callus bridging in three of four cortices over the fracture site on two radiographic
views. If there is disagreement amongst the two surgeons, the X-rays shall be reviewed by a
third surgeon whose opinion shall be final. For fractures that have failed to unite at
twelve weeks, their surgeons will be contacted to determine union rate at six months and
their plain X-rays will be collected and reviewed. If they have undergone any surgery, their
medical records and operation reports will be examined to determine the reason for the
surgery and the exact operation undergone. This is to ascertain surgical revision rate and
union rate at 12, 26 and 52 weeks post injury.
Potential Significance:
If shown to be effective, this device may become a common adjunct to the management of tibia
fractures and significantly decrease the rate of revision surgery and increase the rate of
union seen with these fractures. It may also be considered for use in other long bone
fractures.
