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

NCT ID: NCT01495962

Last Updated: 2016-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2015-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Botulinum Toxin A injection

Group Type: ACTIVE_COMPARATOR

Botulinum Toxin Type A

Intervention Type: DRUG

Six 25 cc injection of Botulinum Toxin A

Placebo (Normal Saline) injection

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo (Normal Saline)

Interventions

Botulinum Toxin Type A

Six 25 cc injection of Botulinum Toxin A

Intervention Type: DRUG

Placebo

Placebo (Normal Saline)

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Martin D. Zielinski

Assistant Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martin D Zielinski, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

David Dries, MD

Role: PRINCIPAL_INVESTIGATOR

Regions Hospital

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Regions Hosptial

Saint Paul, Minnesota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26813298 (View on PubMed)

Other Identifiers

10-008404

Identifier Type: -

Identifier Source: org_study_id