Bioventus EXOGEN Guia Del Usuario página 24

CLINICAL STUDIES
Treatment of Non-union Fractures
Study design
Three prospectively designed studies, undertak-
en in the USA, Germany and the Netherlands,
were submitted to the FDA as the basis for
1
approval of the EXOGEN Ultrasound Bone
healing system to treat established non-unions.
The studies had a self-paired control design with
each non-union case serving as its own control,
and with the prior treatment result of failed
orthopedic care as the control compared to
ultrasound as the only new treatment. The
criterion for the definition of non-union cases was
the minimum time from fracture of nine months.
The primary efficacy outcome was healed due to
EXOGEN treatment, as judged clinically (no pain
upon palpation or weightbearing) and radiograph-
ically (3 out of 4 cortices bridged).
Clinical results
Analyzing the data from Germany, the completed
cases had a healed rate of 86% (64/74) with a
mean time to a healed fracture of 163±9.4 days.
The median heal time was 142 days with a range
of 53 to 375 days. The mean fracture age for the
healed cases was 494 days with a range of
257-6011 days. The scaphoid non-union heal rate
of 33% (2/6) was attributable to the three
scaphoid non-union failures that were all more
than 10 years in fracture age and, therefore, were
very difficult and challenging cases. Cases with
metal surgical fixation present during EXOGEN
treatment such as those with ORIF (Open
Reduction Internal Fixation) and those cases
with intramedullary rods had an 88% (21/24)
and 100% (16/16) healed rate, respectively. The
results of this non-union paired design clinical
study established the safety and effectiveness
of the EXOGEN bone healing system in treating
non-unions. This includes cases that had long
fracture ages of up to 5 years but suggests that
non-unions over 5 years duration may have a
decreased response to ultrasound treatment.
The results are summarized in Table 1.
Nolte et al. , reporting on the Netherlands study,
2
confirmed the 86% (25/29) success rate and
showed the average heal time to be around 5
months without additional intervention. Average
21
non-union fracture age was 61 weeks. There
were high success rates seen with atrophic and
oligotrophic non-unions (80% and 92% respec-
tively) where some biological deficiency may
contribute to the original non-union. Additionally
the application of EXOGEN to hypertrophic
non-unions, which might usually be considered
as requiring revised treatment to correct fracture
instability, was successful in 80% of cases.
Success was seen for a range of bones, all types
of typical primary fracture management, and
across all patient age ranges. For the United
States study, the completed cases group had
an 82% (352/429) heal rate.
Other non-union studies:
Frankel and Mizuno in their analysis of the 1,546
3
USA patient nonunion registry demonstrated that
for patients with risk factors that may impair
fracture healing, such as substance abuse,
diabetes, vascular problems, or steroid use, there
was no significant change in the efficacy of the
EXOGEN Ultrasound Bone Healing System.
Again high success rates were achieved for all
bones, regardless of fracture age, but there was a
trend towards higher success rates and faster
healing with earlier intervention.
Duarte et al. presented data from one of the
4
largest cohorts of patients treated with low
intensity pulsed ultrasound (1996). 380 nonre-
sponding delayed and non-unions (averaging 14
months old) were treated with the EXOGEN
ultrasound signal and achieved an 85% success
rate across a range of bones.
Romano et al. reported on prospective longitudi-
5
nal studies in infected non-unions and pseudoar-
throsis respectively, suggesting high success
rates with low intensity pulsed ultrasound in both
situations.
Strauss and Gonya described the effects of low
6
intensity pulsed ultrasound on two difficult cases
of Charcot non-unions with multiple prior failed
surgical procedures. Both cases healed within 5.5
months when treated with the EXOGEN bone
healing system.
A number of clinical studies have explored the
use of low-intensity pulsed ultrasound in
non-union fractures with instrumented fixation,
fragility fracture or bone infection. The results
have been demonstrated to be comparable to
non-union healing rates in patients without these
particular confounding factors. The heal rate
among the subject patient populations was 80%
(578/719) for instrumented fractures
(145 of 158) for fragility fractures63, and 80%
(47/59) for infected fractures
2,54,58,64-65
heal rate of 82%.
Acceleration of Conservatively
Treated Fresh Distal Radius
Fractures
Study design
Placebo-controlled, randomized, double-blind
multi-centre study with the prospectively defined
primary end-point of a combination of clinical and
radiographic healing (4 out of 4 cortices bridged
as judged by the blinded principal investigator).61
patients with conservatively treated cancellous
radial fractures were randomized into the
EXOGEN treated and control groups
(Kristiansen et al. ).
7
Patient population and demographics
The demographics of the trial participants were
comparable across treatment and control groups
with regard to age, sex, fracture characteristics,
interval between fracture and commencement of
fracture, and duration of follow-up.
Evaluation schedule
Treatment was started within seven days of the
fracture, and patients instructed to use EXOGEN
until the 10 week follow-up visit. Duration of
immobilization in the cast was determined by
the site investigator.
Patients were scheduled to return for follow-up at
1, 2, 3, 4, 5, 6, 8, 10, 12 and 16 weeks.
Clinical Results
EXOGEN treatment accelerated healing by 38%
(61±3.4 days in the active group versus 98±5.2
days in the control group; p<0.0001).
The effect of EXOGEN low intensity pulsed
ultrasound on fracture reduction during healing
was also assessed. The sub-set of fractures
which were satisfactorily reduced having
presented with at least 10 degrees of negative
volar angulation were analyzed. The active group
, 92%
2,30,52-62
for a combined