Prevention of PostAmputation Pain with Targeted Muscle Reinnervation (PreventPAP trial): A national, multicenter, randomized, sham-controlled superiority trial, comparing standard neurectomy with targeted muscle reinnervation in amputations of the lower extremities.

In the Netherlands, every year approximately 3300 lower extremity amputations
(sacroiliac to forefoot) are performed. In current amputation practice the
nerves are cut, without employing any nerve surgical techniques to prevent the
development of chronic pain due to neuroma formation. Around 61% of the
patients with a transtibial or transfemoral amputation develop postamputation
pain (PAP). PAP is a severe lifelong disabling condition profoundly affecting
quality of life.
Microsurgical nerve handling can prevent formation of a painful neuroma and its
sequelae. The last years Targeted Muscle Reinnervation (TMR) is the most
frequently studied technique for patients with amputation pain with promising
results. TMR involves the rerouting of a cut mixed nerve end to a functional
motor nerve, with this preventing neuroma formation.
The expected benefit of implementing TMR during amputation surgery is a
significant reduction of the incidence of PAP. Prevention of this chronic pain
syndrome will lead to a significant improvement in quality of life,
participation in family life and society and reduction of health-related costs
for thousands of amputation patients every year. To achieve this, a
transformation of nerve handling during amputation is needed. With the proposed
study we can make this happen.

To compare postamputation pain (phantom limb pain and residual limb pain) one
year postoperatively in patients receiving a lower extremity amputation with
standard neurectomy versus those who received targeted muscle reinnervation.

A national, multicenter, randomized, sham-controlled superiority trial

Patients with a lower extremity amputation are randomized in either standard
neurectomy or targeted muscle reinnervation (TMR). With TMR each transected
nerve is identified after amputation and is dissected proximally for length. A
nerve stimulator is used to identify functional motor nerve branches. Near the
point where the motor branch enters the muscle, the motor nerve branch is
transected and an end-to-end coaptation is performed with a nearby amputated
nerve.

The additional risks of performing TMR during amputation are negligible. TMR
can be performed at any level of the lower extremities with a standardized
technique. For TMR to be possible, in upper leg amputations, an additional
incision (ca 10 centimeters) has to be made on the dorsal side of the leg,
medial tot the sartorius muscle. To properly blind study participants a
superficial incision for upper leg amputations must also be performed in the
control group. In our experience this will not result in more postoperative
pain or difficulty in sitting. Another factor that will differ from current
standards is that the procedure will take 30 to 90 minutes longer. The extra
time investment will depend on technical aspects related to the level of
amputation and surgeon experience. Although an increase in surgical time of
this length is associated with a slightly higher risk of infection, studies
have not found more complications in patients undergoing acute TMR compared to
those receiving standard care. The burden of the study is minimal, as
participation only requires patients to fill out multiple online questionnaires
at five evaluation moments (at 2 weeks, and at 3, 6, 9, and 12 months).
Prophylactic TMR results in a reduction of the chance to develop PAP. The risks
and the burden for patients are negligible.