Primary Objective: Primary objective of this trial will be to determine whether iNPWT reduces the number of patients with clinically relevant* SSOs after (potentially) contaminated ventral hernia repair
ID
Source
Brief title
Condition
- Abdominal hernias and other abdominal wall conditions
- Bacterial infectious disorders
- Skin and subcutaneous tissue therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome of the PRESSURE trial will be the percentage of patients with
clinically relevant* SSO <30 days after surgery.
*A SSO is considered clinically relevant when the attending physician considers
the SSO of being of such severity that it needs further action for purposes of
clinical diagnosis (other than clinical examination) or treatment, such as
ultrasound/CT, antibiotics, drainage or surgery. Imaging will only be counted
if followed by an intervention. The term *attending physician* is interpreted
to mean the surgeon(s), infectious disease specialist, other physician on the
case, emergency physician or physician*s designee (nurse practitioner or
physician*s assistant).
For the primary outcome, the following complications are considered SSO:
• Superficial SSI as defined by the CDC, but with the minor modification that
opening of the wound doesn*t count as SSI when not being proven by culture.
Cultures are imperative upon opening of the wound by clinicians58:
Infection of skin and subcutaneous tissue of the incision
AND the patient has at least one of the following:
a. Purulent drainage from the incision
b. Organisms identified from an aseptically obtained specimen from the
superficial incision or subcutaneous tissue by a culture or non-culture based
microbiologic testing method which is performed for purposes of clinical
diagnosis or treatment. Patients will be instructed by the investigators to
inform their clinical caretakers that their wounds may ONLY be opened when an
aseptically obtained specimen is taken from their incision as well.
AND
The patient has at least one of the following signs of symptoms: pain
or
tenderness; localized swelling; erythema; or heat. A culture or
non-culture
based test that has a negative finding does not meet this criterion.
d. Diagnosis of a superficial incisional SSI by the attending physician
or other designee.
When superficial SSI is diagnosed it is determined whether the superficial
SSI is accompanied by clinically relevant dehiscence or not, which is
registered afterwards.
• Deep incisional SSI defined by the CDC, but with the minor modification that
opening of the wound doesn*t count as SSI when not being proven by culture.
Cultures are imperative upon opening of the wound by clinicians58:
Infection involves deep soft tissues of the incision (e.g., fascial and muscle
layers)
AND
Patient has at least one of the following:
a. Purulent drainage from the deep incision.
b. A deep incision that spontaneously dehisces, or is deliberately opened or
aspirated by a surgeon, attending physician or other designee and organism is
identified by a culture or non-culture based microbiologic testing method which
is performed for purposes of clinical diagnosis or treatment (e.g., not Active
Surveillance Culture/Testing (ASC/AST). Cultures are imperative upon opening of
the wound. When a wound dehisces and culture is negative it will be recorded
not as SSI but as wound dehiscence.
AND
Patient has at least one of the following signs or symptoms: fever (>38°C);
localized pain or tenderness. A culture or non-culture based test that has a
negative finding does not meet this criterion.
c. An abscess or other evidence of infection involving the deep incision that
is detected on gross anatomical, histopathologic exam, or imaging test
• Wound cellulitis
Defined as wound erythema treated with antibiotics without requiring
manipulation or opening of the incision
• Wound dehiscence
Defined as the splitting apart of the margins of the wound in the absence of
meeting SSI criteria, for which action has been undertaken (e.g. surgery)
• Enterocutaneous fistulae
Defined as a connection between bowel and abdominal wall not deliberately
created during surgery
• Seroma
Defined as a seroma for which action has been undertaken (e.g.
drainage/imaging, etc)
• Hematoma
Defined as a hematoma for which action has been undertaken (e.g.
drainage/imaging, etc)
• Skin ischemia/necrosis
Defined as signs of ischemia (the six P*s: pain, pallor, pulseless,
paraesthesia, paralysis, poikilothermia (not being able to regulate temperature)
SSO monitoring
Monitoring will take place with active patient-based surveillance by a
combination of ante- and post-discharge surveillance methods:
• Examination by the physician during admission and after discharge in the
outpatient clinic at post-operative day 30
• Review of medical records
• In case of suspicion of SSO after discharge the patient will be assessed in
the outpatient clinic. Control patients will undergo the same amount of planned
evaluations for SSO as the intervention group in order to prevent bias.
Secondary outcome
The following secondary outcomes will be assessed in the outpatient clinic at
30 and 90 days and 1 year after surgery:
• The individual components of SSO at <30, <90, <1 year after surgery as
defined above
• Recurrence at 1 year after surgery (= hernia recurrence + bulging)
Clinically relevant bulging will be defined as bulging, in absence of
incisional hernia recurrence, of such a severity that it is an indication for
surgery. For hernia recurrence we propose using the definition of the European
Hernia Society (EHS): **any abdominal wall gap with or without a bulge in the
area of a postoperative scar perceptible or palpable by clinical examination or
imaging.** Hernia recurrence will be proven upon clinical suspicion using
ultrasound or CT imaging as is current standard practice.
• The percentage of patients with any signs of SSO yes/no on photographs
Patients will be asked to take photos of their abdomens and wound upon removal
of the iNPWT/conventional dressing at post-operative day 7 and every week
thereafter and when they present themselves for assessment using standardized
instructions (allows for blinded outcome assessment).
Smartphone ownership is suspected to be high among patients. Furthermore,
smartphone camera quality has been shown to be comparable to regular consumer
level digital cameras in the last several years.59 The photos will be uploaded
using the Castor electronic data capture system63, which is a fully certified
data center (ISO 27001:2013, ISO 9001 and NEN7510), and is the same electronic
data capture system that will be used for the rest of the data collection.
• Peri-incisional SSO
Defined as surgical site occurrences, as defined for our primary outcome, of
the incisional area only.
It seems logical to assume iNPWT mainly acts on tissue in proximity of the
iNPWT, while further lateral in the abdominal wall there is no to little
effect. This notion is also substantiated by a retrospective study from our
institute where the effect of the intervention was predominant in tissue
beneath the iNPWT dressing.63 This is important to consider because abdominal
wall surgery frequently involves surgery of abdominal wall areas unable to
receive iNPWT, increasing the risk of developing SSO in these areas. By looking
only at overall SSO, SSO in these areas may cloud detection of the effect of
iNPWT on the tissue that actually received treatment with the investigational
intervention.
• Skin closure at post-op day 30 on photograph
Skin closure will be defined as complete re-epithelialization throughout the
incision.
• Scar quality on photograph at 1 year postoperative using a Visual Analog
Score and blinded outcome assessment60
• Frequency and type of procedures related to SSO
Surgical procedures, percutaneous drainage, diagnostic procedures (e.g.
CT/ultrasound, wound culture) will be registered as a way to quantify wound
morbidity.
• Hospital stay after surgery in days
• Emergency department visits after discharge
• Readmission within 30 days, 90 days and within a year for any complication
• 30-day, 90-day, in-hospital and 1-year mortality
• Non SSO-complications
Complications as pneumonia, ileus, AKI, IAH/ACS and thrombo-embolic events will
be registered as well and graded according to the Clavien-Dindo classification
as modified by the European Hernia Society.
• Quality of life pre-operatively and at 1 year postoperatively using the
EQ5D-5L questionnaire
• Cost-effectiveness 1 year after surgery (see cost protocol)
Background summary
In a 2010 article, the Ventral Hernia Working Group stated that primary
outcomes in ventral hernia repair are considered to be hernia recurrence as
well as surgical site occurrences (SSO), because of their significant influence
on recurrence.1 With an incidence of 38% and 49% in Ventral Hernia Working
Group grade 3 and 4, SSOs are an excessively frequent problem in abdominal wall
reconstruction.2 Unfortunately, SSOs lack a clear definition in the
literature.3 Nevertheless, in the chapter *Managing Complications of Open
Hernia Repair* of the recently published book *Hernia Surgery - Current
Principles* from Novitsky4, the following short term complications regarding
the surgical site are mentioned:
• SSI as defined by the CDC5
• SSI as in wound cellulitis (as in wound erythema treated with antibiotics
without requiring manipulation or opening of the incision, falls out of the
current CDC SSI criteria)
• Wound dehiscence
• Enterocutaneous fistulae
• Seroma
• Hematoma
• Skin ischemia/necrosis
Of these SSOs, SSI has been shown to be the most significant predictor of
recurrence, with recurrence of up to 80% compared with 34% for those without
SSI.6,7 It is also the most common reason for hospital readmission following
open ventral hernia surgery.8-10 Although data about the costs of SSO as a
whole are lacking, a Centers for Disease Control and Prevention health care
survey found roughly 157,500 SSI*s associated with inpatient operations of the
general population in 2011 in the United States.11 With an average attributable
financial cost of SSI of $20,785 per case, this leads to an overwhelming
$3,273,637,500 annually for the United States alone.12 Strikingly, SSI is
associated with mortality, which is 3% in all of surgical patients. Because of
the frequent co-morbidities in this field, it is likely to be much higher in
ventral hernia repair. Furthermore, studies with long-term follow-up have
demonstrated a dramatic increase in recurrence rate after SSI.9,13,14
Another particular frustrating complication following ventral hernia repair are
seromas, with a prevalence proven to be as high as 100% on routine ultrasound
exams postoperatively.15 Although not all seromas are clinically relevant,
seromas can be a bothersome postoperative problem. Furthermore, seromas may
prevent the ingrowth of mesh and thus add to the risk of recurrence, and may
become inoculated with bacteria through the surgical wound or iatrogenically
from repeat fluid aspirations.15
Since 2006, negative pressure wound therapy (NPWT) has been applied on surgical
incisions (incisional NPWT, in short iNPWT) in order to reduce the amount of
SSOs, with promising results in the literature.16-21 iNPWT is also known as
prophylactic negative pressure wound therapy (pNPWT) and closed incision
management (CIM).
Although to some it might seem counter-intuitive to apply negative pressure
wound therapy to a primarily *closed* wound, one should consider that strictly
seen, the wound is still open. Indeed, no matter how perfectly restored the
underlying tissues may be, a wound should be considered to be really closed
only if restoration of an intact epidermal barrier, called *re-
epithelialization*, has been established.22 To ascertain this, wound healing
occurs through several overlapping phases: hemostasis, inflammation,
proliferation and maturation.23 Only in the proliferative phase, which just
starts on day two after injury and normally lasts up to 3 weeks in the normal
cutaneous wound, re-epithelialization occurs.22
Considering this, primary *closed* surgical incisions are actually open wounds
for a considerable amount of time, albeit relatively small ones compared to
non-surgically closed wounds, for which NPWT was used originally.24 Yet, for
the past decades, the mainstay of incisional wound care has been an simple
adhesive gauze based dressing, and it currently still is (although use of wound
glue as a dressing is rising in the UK).25,26 Remarkable in this context, one
study has shown that bacteria are able to penetrate even up to 64 layers of
gauze dressing.27
iNPWT devices generally consist out of foam, adhesive drapes and a vacuum pump
with connected tubing. The working mechanism roughly consists of two
components: on the one hand by applying subatmospheric (also called *negative*)
pressure on the wound, on the other by creating a barrier between the wound and
the external environment with the adhesive film.
The negative pressure has several supposed working mechanisms: it approximates
the underlying tissue and skin edges, thus reducing any dead space (which makes
the micro-environment of the wound less susceptible for microbial
proliferation). Furthermore, the negative pressure reduces lateral stress28,
reducing the risk of dehiscence. Perfusion has been measured to be increased,
possibly providing in the raised need for oxygen in a healing wound.29
Moreover, it removes any excess fluid, which benefits oxygenation and healing
as well30, and results in less, and smaller seromas.31
Additionally to the benefits of negative pressure, the barrier provided by the
adhesive film reduces the risk of external contamination into the wound,
resulting in less contamination with skin flora.32 The barrier also prevents
evaporation, thus keeping the wound moist, which is thought to accelerate
healing.33
Altogether, it seems that iNPWT is a promising technique for reducing surgical
site complications, hospitalization length, as well as costs. Nonetheless,
although several randomized controlled trials have been conducted in clean
orthopedic surgery34-38, no RCTs have compared iNPWT with conventional
dressings in contaminated surgery up to our knowledge.
We hypothesize that iNPWT reduces the incidence of SSOs, length of stay,
readmission and costs in contaminated abdominal wall reconstruction.
Study objective
Primary Objective:
Primary objective of this trial will be to determine whether iNPWT reduces the
number of patients with clinically relevant* SSOs after (potentially)
contaminated ventral hernia repair <30 days after surgery.
*A SSO is considered clinically relevant when the attending physician considers
the SSO of being of such severity that it needs further action for purposes of
clinical diagnosis (other than clinical examination) or treatment, such as
ultrasound/CT, antibiotics, drainage or surgery. Imaging will only be counted
if followed by an intervention. The term *attending physician* is interpreted
to mean the surgeon(s), infectious disease specialist, other physician on the
case, emergency physician or physician*s designee (nurse practitioner or
physician*s assistant).
Secondary Objective(s):
Secondary objectives are:
- to determine whether iNPWT reduces the amount of SSOs and its individual
components <90 days and 1 year after surgery
- to investigate whether it leads to less clinically relevant bulging or hernia
recurrence 1 year postoperatively
- to investigate if it reduces the need of interventions for SSO
- to investigate whether iNPWT reduces length of stay after surgery, emergency
department visits and readmissions after discharge
- to investigate whether it leads to a better quality of life for hernia
patients 1 year after surgery.
- to investigate whether it is cost-effective in contaminated abdominal wall
reconstruction
Study design
STUDY DESIGN
This study will be a investigator-initiated, multinational, multicenter,
randomized controlled clinical trial in our collaborative international network
with superiority design, in which eligible patients will be randomized to
receive iNPWT or a wound dressing as according to local hospital policy (a
pragmatic approach) using block randomization and stratification based on
hospital site while using an open label design for the primary outcome
(presence of SSO <30 days). Prolonged follow-up will be at <90 days and <1 year
postoperative.
Apart from the open label primary outcome, we propose blinded outcome
assessment of photographs taken from the abdomens of patients for assessment of
SSO as can be judged by photograph. For example, patients may be instructed to
take a photograph of their abdomen every following week after surgery (post-op
day 7, 14, etc) for up to one month, and when they present themselves for
assessment. If these results point in the direction of the open label primary
outcome results this will be a strong argument for our study.
The duration of the study is estimated to be 2,5 years.
It will be ensured that the study protocol will adhere to the SPIRIT statement
regarding interventional trials. Trial registration will occur at
Clinicaltrials.gov as well as TrialRegister.nl.
Intervention
Patients participating in this trial will be randomized to:
Treatment group A
The intervention group will receive a commercially available Prevena* Incision
Management System (Kinetic Concepts Inc. (Acelity), San Antonio, TX, USA),
placed in sterile conditions after closure of the skin during surgery. The
interventional product will remain in situ for 7 consecutive days
postoperatively at -125 mm Hg continuous subatmospheric pressure, irrespective
of hospital discharge.
This device has been tested both in non-clinical as clinical studies and is
already in use in the coordinating center (Academic Medical Center - The
Netherlands) in patients undergoing abdominal wall reconstruction.
Any concern about the wound or device will require removal of iNPWT earlier
than planned and will be recorded as a secondary endpoint of the trial.
Treatment group B
The control group will receive conventional wound dressings, defined as a
simple, sterile, gauze based dressing, as is locally available and routinely
used at the participating center.
Moreover, participating sites and patients will be instructed to not manipulate
or touch the wound when not strictly indicated for clinical purposes, and to
not remove the dressing (e.g. for inspection) unless it is clearly indicated,
or soaked by wound exsudate.
By demanding the dressing to be a simple gauze based dressing, we presume no
large confounding factors will be present. Moreover, according to a Cochrane
review recently updated in December 2016, there is no evidence to conclude one
wound dressing is superior over any other in preventing SSI at this moment.43
Nonetheless, advanced dressings (e.g. vapour-permeable films, hydrocolloid
dressings, fibrous hydrocolloid dressing, polyurethane matrix hydrocolloid,
wound glue or antimicrobial dressings) are excluded. Furthermore, realizing a
uniform dressing for all patients may prove difficult because this will be an
international trial in various hospitals whose material departments may not
have the same dressing available.
Study burden and risks
In general, iNPWT is tolerated well by patients and is considered to be safe.13
Although one study36 has described blister formation after the application of
iNPWT, no other studies have reported replicating this finding. With an
adequate placement technique, blisters have not been seen.
In theory it is also possible that placement of iNPWT amplifies bleeding in
case of inadequate hemostasis at the incisional site. However, in case of
bleeding, the iNPWT will be removed immediately. Furthermore, the iNPWT units
contain an acrylic adhesive coating and a skin interface layer with silver,
which may present a risk of an adverse reaction in patients who are allergic or
hypersensitive to acrylic adhesives or silver. Additionally, the iNPWT dressing
contains silver that may impair visualization with certain imaging modalities.
The dressing may also impair visual inspection during the first 7 days.
Nevertheless, iNPWT has been shown to be a safe intervention in several
systematic reviews, where the risks described above were not designated to be a
problem.14,57 However, iNPWT does appear to decrease SSI, and possibly other
SSO as well.57
Patients will be asked to take photographs of their abdomen and wound 7 days
after surgery and every week thereafter the first month, when they present
themselves for assessment, as well as after three months and after 1 year.
Participants will be asked to fill out the EQ5D questionnaire pre-operatively,
one and three months postoperatively and 1 year postoperatively.
Furthermore, after three months and after one year patients will be asked to
fill out two questionnaires to assess cost-effectiveness.
Patients will also be asked to fill out the POSAS 2.0 questionnaire 1 month, 3
months and 1 year postoperatively.
Clinical evaluation of patients for SSO and hernia recurrence is part of
routine clinical care and therefore is not viewed as a study procedure.
Outside of the procedures described above, no invasive procedures, laboratory
tests or psychological/psychiatric evaluations will be performed outside of
routine clinical care.
Informed consent will be obtained from every patient.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
In order to participate in this trial, a subject must meet the following
criteria:
• >=18 years
• Informed consent
• Pre-operative CT available (< 12 months of surgery)
• Scheduled for elective, open abdominal wall reconstruction*, And one of the
following:
• A stoma** or enterocutaneous fistula and an abdominal wall defect*** of >6
cm**** on CT
• Violation of the gastrointestinal tract and an abdominal wall defect of >6 cm
on CT
• Infected or exposed mesh (any size)
• Open abdomens with contamination***** (any size), * Operative treatments
may include transversus abdominis release, endoscopic external oblique release
or open external oblique release, as long as the abdominal wall reconstruction
is open. Reconstructions incorporating the pedicled or free transfer of tissue
(e.g. an antero-lateral thigh or latissimus dorsi flap) are included as well.
, ** This includes jejunostomy, ileostomy, colostomy and Bricker stomata. ,
*** Abdominal wall defect is defined as:
**any abdominal wall gap with or without a bulge perceptible by imaging*
This definition is a modification of the definition proposed by the EHS for
incisional hernia recurrence., ****In case of parastomal hernia and the patient
is candidate for ostomy takedown or relocation, the resulting defect in the
abdominal wall should be taken for this measure, ***** Contamination is defined
as CDC Surgical Wound Class II (potentially contaminated) to IV
(dirty/infected).
Exclusion criteria
• Patients <18
• Parastomal hernias planned for reconstruction using a local (or laparoscopic)
approach without a laparotomy*, *In case of a patient scheduled for
reconstruction of both incisional hernia and a parastomal hernia, the
reconstruction of the incisional hernia will be eligible for randomization. If
a parastomal hernia is approached through a laparotomy, the laparotomy incision
will be eligible for randomization.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL60054.018.16 |
| OMON | NL-OMON22141 |