The Biomechanical Effects of Flaccid Paralysis Induced by Botulinum Toxin a After Damage Control Laparotomy

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT01495962

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Wound; Abdomen, Abdominal Wall	Drug: Botulinum Toxin Type A Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

The Biomechanical Effects of Flaccid Paralysis Induced by Botulinum Toxin a After Damage Control Laparotomy: A Pilot Study

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Botulinum Toxin A injection	Drug: Botulinum Toxin Type A Six 25 cc injection of Botulinum Toxin A
Placebo Comparator: Placebo (Normal Saline) injection	Drug: Placebo Placebo (Normal Saline)

Arm

Intervention/Treatment

Active Comparator: Botulinum Toxin A injection

Drug: Botulinum Toxin Type A

Six 25 cc injection of Botulinum Toxin A

Placebo Comparator: Placebo (Normal Saline) injection

Drug: Placebo

Placebo (Normal Saline)

Outcome Measures

Primary Outcome Measures

The primary objective of this study is to determine whether BTX will facilitate primary fascial closure after DCL. [2 years]
The primary endpoint is the rate of delayed primary fascial closure. Delayed primary fascial closure will be considered when the rectus abdominus fascia is directly approximated in the midline during the same hospitalization as the initial DCL without the use of mesh.

Secondary Outcome Measures

Non-invasive biomechanical testing results (surface wave elastography, traction index and durometry) [2 years]
Mortality [2 years]
Duration of mechanical ventilation [2 years]
Complications (wound infection, fascial dehiscence, enterocutaneous fistula formation, acute renal failure, pneumonia) [2 years]
Overall hospital cost [2 years]
Total narcotic use (morphine equivalents) [2 years]
ABPS score [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)