Clinical trial NCT05615844: Antibiotic Cement Bead Pouch Versus Negative Pressure Wound Therapy
Official title: A Randomized Controlled Trial Comparing Antibiotic Cement Bead Pouch Versus Negative Pressure Wound Therapy for the Management of Severe Open Tibia Fracture Wounds
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Open tíbia Fracture
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: McMaster University
First posted: 2022-11-14
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Beads vs Vac trial is a multi-centre randomized controlled trial of 312 participants with a severe open tibia fracture requiring multiple irrigation and debridement surgeries. Eligible participants will be randomized to receive either an antibiotic bead pouch or negative pressure wound therapy (NPWT) for their temporary open fracture wound management. Outcomes will be assessed at 6 weeks, 3 months, and 6 months post-surgery. The primary outcome will be a composite outcome to evaluate clinical status six months after randomization. Components of the composite outcome will be hierarchically assessed in the following order: 1) all-cause mortality, 2) injury-related amputation of the lower extremity, 3) unplanned reoperation to manage wound complications, infection, or delayed fracture healing, and 4) clinical fracture healing as assessed using the Functional IndeX for Trauma (FIX-IT) instrument. The secondary outcomes will independently assess the four components of the primary outcome. This is a Phase III trial.

Detailed description: The primary objective of early open fracture management is to minimize the risk of complications. In severe cases, multiple irrigation and debridement surgeries are required to overcome the severe wound contamination, to reassess the evolving tissue injury, and/or to temporize and plan appropriate soft tissue coverage with a skin graft or muscle flap. When multiple irrigation and debridement surgeries are needed, there is uncertainty on how the open fracture wound should be managed between procedures. Negative pressure wound therapy (NPWT), commonly known as a Wound VAC, is the preferred method of open fracture wound management for most surgeons. Opponents of NPWT believe that NPWT desiccates the open fracture wound and rapidly removes any local antibiotics placed in the wound during surgery. Instead of using NPWT, they place temporary non-absorbable antibiotic-laden cement beads into the open fracture wound and seal it with a large occlusive dressing. This wound management strategy is known as an antibiotic cement bead pouch, or more commonly a Bead Pouch. Mounting evidence questions the effectiveness of NPWT to prevent open fracture complications. Additionally, emerging comparative studies suggest the antibiotic bead pouch may significantly reduce the risk of infection compared to NPWT. This trial seeks to fill this critical knowledge gap.

The primary objective of this trial is to determine if the antibiotic bead pouch, compared to NPWT application, is more effective at reducing open tibia fracture complications. The primary outcome will be a composite outcome to evaluate clinical status six months after randomization. Components of the composite outcome will be hierarchically assessed in the following order: 1) all-cause mortality, 2) injury-related amputation of the lower extremity, 3) unplanned reoperation to manage wound complications, infection, or delayed fracture healing, and 4) clinical fracture healing as assessed using the Functional IndeX for Trauma (FIX-IT) instrument. The secondary objectives will independently assess the four components of the primary outcome.

The trial population includes patients 18 years and older with a severe open tibia fracture requiring more than one irrigation and debridement and being treated with internal or external fixation for definitive fracture management. Patients who have contraindications to the NPWT or local intrawound antibiotics will be excluded.

312 participants will be randomized in a 1:1 ratio to receive either an intraoperative antibiotic bead pouch or negative pressure wound therapy (NPWT). Participants will receive their allocated wound management strategy at the conclusion of their first irrigation and debridement procedure. Participants will have follow-up assessments at 6 weeks, 3 months and 6 months post-fracture.

The primary outcome will be a composite outcome to evaluate clinical status six months after randomization. Components of the composite outcome will be hierarchically assessed in the following order: 1) all-cause mortality, 2) injury-related amputation of the lower extremity, 3) unplanned reoperation to manage wound complications, infection, or delayed fracture healing, and 4) clinical fracture healing as assessed using the Functional IndeX for Trauma (FIX-IT) instrument. The secondary outcomes will independently assess the four components of the primary outcome. An Adjudication Committee will review all primary and secondary endpoints and a Data Safety Monitoring Committee (DSMC) will review all safety events.

Eligibility criteria: The inclusion criteria are:

1. Patients 18 years of age or older.
2. Severe open tibia fracture requiring more than one irrigation and debridement procedure to treat the open fracture.
3. Planned internal or external fixation for definitive fracture management.
4. Formal surgical debridement within 72 hours of their injury.
5. Will have all planned fracture care surgeries performed by a participating surgeon or delegate.
6. Informed consent obtained.

The exclusion criteria are:

1. Due to the severity of injury, the treating surgeon does not believe limb salvage \>6 months is likely to be successful based on the emergency department or initial intraoperative assessment (prior to enrolment and randomization).
2. Medical contraindication to antibiotic beads, including previously known allergies or sensitivities to vancomycin and/or tobramycin.
3. Medical or injury contraindication to NPWT. Injury contraindications could include situations in which the NPWT could not be placed over a vascular graft or exposed neurovascular structure.
4. Received previous surgical debridement or management of their fracture at a non-participating hospital or clinic (as applicable).
5. Chronic or acute infection at or near the fracture site at the time of initial fracture surgery.
6. Incarceration.
7. Women of child-bearing potential who are pregnant or intending to become pregnant within the next 6 months.
8. Currently enrolled in a study that does not permit co-enrollment.
9. Unable to obtain informed consent due to language barriers.
10. Anticipated problems, in the judgment of research personnel, with maintaining follow-up with the patient.
11. Prior enrollment in the trial.
12. Other reason to exclude the patient, as approved by the Methods Center.

Primary outcomes:
measure: Clinical status
timeFrame: 6 months
Secondary outcomes:
measure: Mortality
timeFrame: 6 months
measure: Amputation
timeFrame: 6 months
measure: Unplanned reoperation(s)
timeFrame: 6 months
measure: Clinical fracture healing
timeFrame: 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland, R Adams Cowley Shock Trauma Center
state: Maryland
city: Largo
country: United States
facility: University of Maryland Capital Region Health
state: Maryland
city: University
country: United States
facility: University of Mississippi
state: Mississippi
city: Lincoln
country: United States
facility: Bryan Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Bon Secours Mercy Health
state: Ohio
city: Portland
country: United States
facility: Ortegon Health & Science University
state: Oregon
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: Inova Fairfax
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
Study officials:
References: