VACuum-Assisted Closure for Necrotizing Soft Tissue infecTIONs (VACATION)

Intro: Necrotizing and soft tissue infections (NSTI) are life-threatening bacterial infections characterized by subcutaneous tissue, fascia or muscle necrosis. The hospital mortality of NSTI is high, comprised between 20 and 30%. NSTIs represent the 4th cause of septic shock. Early management of NSTIs requires a coordinated and multidisciplinary approach, including broad-spectrum antibiotic administration, management of organ failures and aggressive surgical debridement with excision of all necrotic and infected tissues. NSTIs involve the lower limbs in about 70% of cases and lead in 15% of cases to limb amputation. During the early post-operative phase, daily wound care is required using conventional dressings. As soon as the infectious process is controlled, typically within 7 to 10 days of the initial debridement, the main goal of wound dressing is to allow for a granulation tissue to develop so that to perform a skin grafting. Negative pressure wound therapy (NPWT), which consists in applying a negative pressure on the wound surface, may be used to this effect. A dedicated dressing is connected to a device that generates a negative pressure and collects exudates. NPWT may have a positive effect on wound healing by removing exudate, increasing regional perfusion and patient comfort and reducing infections. Beneficial effects of NPWT have been suggested by case series. However, no randomized controlled trial are currently available to adequately assess its efficiency and the 2014 guidelines of the Infectious Diseases Society of America (IDSA) on NSTI did not provide recommendations regarding NPWT use for managing NSTI wounds. The study's hypothesis is that in patients managed for NSTIs, NPWT: 1) may accelerate skin grafting and complete wound healing; and 2) improve functional outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Necrotising Soft Tissue Infections
• Intervention / Treatment: Other: Negative pressure wound therapy (NPWT); Other: Conventional dressing

Detailed Description

Hypothesis/Objective: To demonstrate in patients who underwent a surgical debridement of the lower limb for NSTI a superiority of a wound dressing strategy using NPWT (intervention) as compared with conventional wound dressing on local healing (complete) and the recovery of walking.

Method: Open-label randomized controlled trial with blinded assessment of the primary end point. Randomization in two arms: experimental group (NPWT) versus control group (conventional dressing) until skin grafting (decided by the attending surgeon).

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicolas DE PROST, MD, PhD; Phone Number: + 33 1 49 81 23 89; Email: nicolas.de-prost@aphp.fr
• Study Contact Backup: Name: David SCHMITZ; Phone Number: + 33 1 49 81 36 32; Email: david.schmitz@aphp.fr

Study Locations

• France
  • Créteil, France, 94010 Créteil Cedex
    • Assistance Publique Hôpitaux de Paris - CHU HENRI MONDOR
    • Contact: Nicolas DE PROST, MD, PhD; Phone Number: :+ 33 1 49 81 23 89; Email: nicolas.de-prost@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Written informed consent
• NSTI/NF of the lower limb clinically suspected and confirmed by surgery with a first debridement performed since 5 days or more
• Infection considered controlled (i.e., no more surgical debridement is necessary)
• Last debridement performed at least 72 hours before
• Affiliation to a social security system

Exclusion Criteria:

• Limited life expectancy
• NPWT already initiated for the current NSTI/NF episode
• 1st surgical debridement performed less than 5 days or more than 15 days before
• High risk of bleeding (blood vessels exposed)
• Local neoplasia
• Risk of organ or peripheral nerve injury
• Impossibility to set up a NPWT dressing hermetically
• Limb amputation
• Patient unable to walk without help
• Women who are pregnant or are breast-feeding, or are of childbearing age and do not use or do not plan to use acceptable birth control measures
• Patients under legal protection
• Prisoners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Negative pressure wound therapy (NPWT); Negative pressure wound therapy (NPWT): an NPWT device will be applied hermetically from randomization to skin grafting.	Other: Negative pressure wound therapy (NPWT); The therapeutic intervention being tested is the use of a negative pressure wound therapy (NPWT) device. Several medical devices are currently being used and are based on the same principle. They involve applying negative pressure, generally between -100 and -150 mmHg, to a wound using a dressing (mostly a polyurethane foam dressing with hydrophobic pores), which hermetically covers the wound's surface and is connected to a container for collecting the fluids drained off. These devices are widely available and used to treat post-operative wounds. Duration of treatment: the use of NPWT will be maintained until the recovery of the skin has been achieved by the skin graft. An average duration of 3 weeks' treatment is expected in the intervention group.
Active Comparator: Conventional dressing; Conventional dressing will be performed from randomization to skin grafting. The dressings will be performed following usual procedures of investigating centers	Other: Conventional dressing; Conventional dressings will be performed from randomization to skin grafting and applied every day based on the methods normally used in the participating centres, and also until the recovery of the skin has been achieved by the skin graft. This generally involves local care provided on a daily basis, ensuring gentle mechanical and chemical debridement by covering the wound with alginate type or other dressings, according to the condition of the wound. The methods used to apply these conventional dressings will be recorded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time elapsed between randomization and the onset of a combined outcome measure including a complete healing of the diseased limb and the recovery of walking.	Complete healing of the diseased limb is defined by more than 90% of functional skin covering the wound and Recovery of walking is defined by the ability to walk at least 100 steps, corresponding to approximately 30 meters, without help	between Day 0 and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activities of Daily Living score		at Day 0, 3 months and 6 months
Short Form - 36		at Day 0, 3 months and 6 months
Pain assessment	Pain assessment at each wound care by the patient (visual analogic scale), the nurse (behavioral pain scale) and quantification of morphine consumption (in morphine base equivalent): measured by the investigator at each wound care	between Day 0 and 3 months
Quantification of the number of anesthesia procedures (general anesthesia, sedation)		between Day 0 and 6 months
Time elapsed between randomization and skin grafting		between Day 0 and 6 months
Number of local superinfection episodes		between Day 0 and 3 months
Quantification of the walking capacity	measured over one week with a pedometer by the research nurse, at 3 and 6 months	at 3 months and 6 months
Duration of hospital stay		between Day 0 and 6 months
Quantification of the time needed for each wound care before randomization and skin grafting	this measure will be recorded once a week for one wound care	between Day 0 and 6 months
Need for stopping the NPWT		between Day 0 and 3 months
Number of surgeries performed between randomization and skin grafting	All surgeries will be recorded, including their date and indication	between Day 0 and 6 months
Number of surgeries performed after skin grafting	All surgeries will be recorded, including their date and indication, all surgeries will be recorded, including their date and indication	between Day 0 and 6 months
Mortality assessed		at 3 months and 6 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Nicolas DE PROST, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2021
• Primary Completion (Anticipated): March 1, 2025
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): October 8, 2021

Study Record Updates

• Last Update Posted (Actual): October 8, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Negative pressure wound therapy; Necrotising soft tissue infections; Necrotising fasciitis
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Soft Tissue Infections
• Other Study ID Numbers: APHP200021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No