Clinical trial NCT01495962: The Biomechanical Effects of Flaccid Paralysis Induced by Botulinum Toxin a After Damage Control Laparotomy
Official title: The Biomechanical Effects of Flaccid Paralysis Induced by Botulinum Toxin a After Damage Control Laparotomy: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Wound; Abdomen, Abdominal Wall
Keywords: Damage Control Laparotomy
Open Abdomen
Botulinum Toxin A
Primary Fascial Closure
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2011-12-20
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Damage control laparotomy (DCL) is a life saving maneuver used with success in trauma and acute general surgery patients. The technique involves source control of sepsis and hemorrhage with an abbreviated laparotomy. In other words, the surgical procedure is cut short to allow for resuscitation in the ICU after the immediately life threatening pathology is treated. Planned re-exploration is then performed within 24-48 hours. It is at this procedure that the injuries are reconstructed. This technique, unfortunately, has several complications implicit with its use including wound infection, enterocutaneous fistula formation, and intra-abdominal abscess development.\[1\] Additionally, in patients whom primary fascial closure is not achieved, extensive abdominal wall reconstruction will be required in 6-12 months. The key for preventing these complications is definitive closure of the abdominal fascia, however, 10-50% of patients will have a planned ventral hernia with an open abdominal wound at dismissal \[1,2\] Proven methods for decreasing the rate of planned ventral hernia utilize tension in the midline to counter the effects of lateral abdominal muscular retraction.\[3,4,5\] Despite these improvements, however, the planned ventral hernia rate continues to be substantial.\[2\] Botulinum toxin a (BTX) is an FDA approved neuron modulating agent which has been used extensively in cosmetic, motor and pain disorders over the past 20 years \[6,7\]. The toxin blocks acetylcholine and pain modulator release (calcitonin gene related peptide and substance P) from the pre-synaptic cholinergic nerve terminal. The peptides are unable to bind at their motor end plate receptors through a process that cleaves proteins involved in the transport protein cascade. This results in flaccid paralysis and neuromodulation of the abdominal wall muscles resulting in reduced lateral tension and pain. Theoretically, this could increase the rates of primary fascial closure, improve pain sensation, decrease the rate of complications associated with open abdomens all while lowering the costs and need for future abdominal wall reconstruction.


Eligibility criteria: Inclusion Criteria

* male or female, aged ≥ 18 years or older
* signed Informed Consent form by appropriate patient representative
* undergone a DCL for trauma or acute general surgery

Exclusion Criteria

* death prior to BTX injection
* failure to achieve hemodynamic stability within 24 hours (stable or decreasing vasopressor support within 6 hours in combination with a stable or improving base deficit or lactate level)
* Viable pregnancy
* At risk populations (\<18 years of age, prisoners)
* BMI \> 50
* Pre-existing pareses (Amyotrophic Lateral Sclerosis, myopathies, motor polyneuropathies
* impaired neuromuscular transmission (Myasthenia Gravis, Lambert-Eaton Syndrome)
* concurrent aminoglycoside use
* chronic obstructive pulmonary disease
* known metastatic malignancy
* pre-existing cirrhosis
* necrotizing fasciitis of the trunk
* hypocoagulable state (INR \>1.5)

Primary outcomes:
measure: The primary objective of this study is to determine whether BTX will facilitate primary fascial closure after DCL.
timeFrame: 2 years
Secondary outcomes:
measure: Non-invasive biomechanical testing results (surface wave elastography, traction index and durometry)
timeFrame: 2 years
measure: Mortality
timeFrame: 2 years
measure: Duration of mechanical ventilation
timeFrame: 2 years
measure: Complications (wound infection, fascial dehiscence, enterocutaneous fistula formation, acute renal failure, pneumonia)
timeFrame: 2 years
measure: Overall hospital cost
timeFrame: 2 years
measure: Total narcotic use (morphine equivalents)
timeFrame: 2 years
measure: ABPS score
timeFrame: 2 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: St. Paul
country: United States
facility: Regions Hosptial
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Martin D Zielinski, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Regions Hospital
name: David Dries, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zielinski MD, Kuntz M, Zhang X, Zagar AE, Khasawneh MA, Zendejas B, Polites SF, Ferrara M, Harmsen WS, Ballman KS, Park MS, Schiller HJ, Dries D, Jenkins DH. Botulinum toxin A-induced paralysis of the lateral abdominal wall after damage-control laparotomy: A multi-institutional, prospective, randomized, placebo-controlled pilot study. J Trauma Acute Care Surg. 2016 Feb;80(2):237-42. doi: 10.1097/TA.0000000000000917.