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

NCT01495962 | Completed Phase 1

• 1 other identifier: 10-008404
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

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.

Conditions

Wound; Abdomen, Abdominal Wall

Keywords

Damage Control Laparotomy; Open Abdomen; Botulinum Toxin A; Primary Fascial Closure

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to determine whether BTX will facilitate primary fascial closure after DCL.

  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.

  2 years

Secondary Outcomes (7)

• 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

Study Arms (2)

Botulinum Toxin A injection

ACTIVE COMPARATOR

Drug: Botulinum Toxin Type A

Placebo (Normal Saline) injection

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Botulinum Toxin Type A DRUG

Six 25 cc injection of Botulinum Toxin A

Botulinum Toxin A injection

Placebo DRUG

Placebo (Normal Saline)

Placebo (Normal Saline) injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (2)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Regions Hosptial

Saint Paul, Minnesota, 55101, United States

Location

Related Publications (1)

• 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.

  PMID: 26813298 DERIVED

MeSH Terms

Conditions

Wounds and Injuries

Interventions

Botulinum Toxins, Type A

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Martin D Zielinski, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• David Dries, MD

  Regions Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Surgery

Study Record Dates

• First Submitted: November 15, 2011
• First Posted: December 20, 2011
• Study Start: November 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: June 1, 2015
• Last Updated: April 27, 2016

Record last verified: 2016-04

Locations

US (2)