Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03932461 |
| Other study ID # |
VACOR2019 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2020 |
| Est. completion date |
September 1, 2027 |
Study information
| Verified date |
November 2023 |
| Source |
Odense University Hospital |
| Contact |
Pooya Rajabaleyan, M.D. |
| Phone |
+4527118889 |
| Email |
pooya.r[@]hotmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Multicenter randomized controlled trial including patients with fecal or diffuse peritonitis
to either vacuum assisted closure or relaparotomy "on-demand".
Description:
Multicenter randomized controlled trial including patients with fecal or diffuse peritonitis*
to either vacuum assisted closure or relaparotomy "on-demand". The aim with our study is to
compare the postoperative complications between vacuum assisted closure and relaparotomy
"on-demand".
Primary endpoint is to compare peritonitis related complications and Comprehensive
Complication Index (CCI) between NPWT treatment (VAC) and conventional treatment (ROD) at 30,
90 days and 1 year.
Secondary outcome parameters are: Mortality at 30, 90 days and 1 year, SOFA score and
C-reactive protein measured the first seven days after index laparatomy, quality of life
after 3 and 12 months (SF-36 questionnaire), ventral hernia after 3 and 12 months. (assessed
by CT) and, hospital care utility within three months after index surgery. A power
calculation was made which concluded that 340 patients should be included.
*Diffuse fecal peritonitis is defined as contamination of 2 out of the 4 abdominal quadrants
with fecal contamination starting from the small intestine, colon or rectum.
Design
A multicenter non-blinded superiority randomized controlled trial on VAC vs. ROD. Danish, as
well as other European centers, will be invited to participate
All patients over 18 with suspected diffuse peritonitis caused by perforation of the small
intestine, colon or rectum with contamination in minimum 2 out of 4 abdominal quadrants, will
be included.
Exclusion criteria are;
- Diffuse peritonitis originating from a different focus than the small intestine, colon
or rectum
- Diffuse peritonitis originating from a perforation on the stomach, duodenum,
gallbladder, appendix, necrotizing pancreatitis, salpingitis, or peritoneal dialysis
- Primary peritonitis
- Immunocompromised (ongoing chemotherapy or prednisolone >20 mg/day)
- Chronic parenchymal liver disease
- Pregnancy
- Patients with end-stage disease
- Laparoscopic surgery (not converted to laparotomy)
- Acute occlusion of superior mesenteric artery
- Peritoneal carcinomatosis
- Abdominal trauma
- Lack of consent from the surgical equipoise
- Local peritonitis confined to 1 quadrant only
Randomization
Patients are included by a surgical equipoise followed by patient information and consent
after recovery. The primary investigator from each site will be contacted by the surgeon
on-call when a patient is scheduled for diagnostic laparoscopy or explorative laparotomy on
suspicion of secondary peritonitis. Patients' fulling inclusions criteria will be randomized
after consent has been obtained by the surgical equipoise. Centers that do not receive
approval from their respective scientific ethics committee to include patients through a
surgical equipoise must obtain informed and written consent before randomization.
Randomization will be web-based via (REDCap ®) in blocks of 2, 4, and 6 stratified for center
and age above or below 65 years. The justifications for stratifying according to the center
are that there might be differences in the surgical treatment, preoperative optimization, and
postoperative treatment both at the ward and intensive care unit (ICU) that might affect the
outcome. The patients will be randomized to either abdominal closure with ROD or open abdomen
with VAC. The randomization tool, along with eligibility criteria, can be accessed through
our website, www.vacor.sdu.dk.
In cases where the surgeon finds that the allocated treatment may be contraindicated or is
judged to harm the patient, it will be left to the surgeon's discretion to choose the most
appropriate treatment. Patients who cannot be treated according to randomization will be
analyzed according to intention-to-treat principles. Any eligible patient not included will
be registered in a screening log.
How to apply Vacuum Assisted Closure (VAC)
The VAC® Abdominal Dressing System (KCI Vacuum Assisted Closure, San Antonio, TX, USA) will
be used. Intestines, including lateral aspects, are covered by the visceral protective layer.
The first layer of foam is placed in the laparostoma on the visceral protective layer and
must extend below the fascia at a distance of 5 cm from the facial opening. Above this, a
minimum of one piece of foam is folded and placed in the laparostoma. Finally, the
laparostoma will be covered by the occlusive drape. A circular opening of approximately 5 cm
in diameter will be created in the drape where the connection tubes to the vacuum pump will
be placed. Simultaneously while applying the negative pressure of 125 mmHg, the wound edges
are approximated manually towards the midline. The dressing will be changed with an interval
of approximately 48 hours as standard or whenever needed according to the clinical condition.
Each dressing change must be performed in the operation theatre with the patient in general
anesthesia and muscle relaxation. Peritoneal fluid must be cultured at each dressing change
and when fascia is closed. The fascia closure will commence as soon as possible according to
the patient's general condition judged by gastrointestinal function, renal function, and a
decline in inflammatory parameters either in one or repeated sessions. The aim will be a
closure of the abdomen within a maximum of 8 days after the index operation.
The fascia closure after VAC-treatment can be according to the Israelssons principle as
described below or upon the surgeon's discretion. A staged closure may start distally,
proximally, or in a combination.
How to do primary closure
The abdominal wall is closed according to the Isreaelsson principle where it is sewn
continuously in the fascia at a distance between the sutures of 5 mm and the distance to the
facade edge of 5-10 mm. Monofilament PDS 0-0 (Ethicon) (or equivalent) is used. The suturing
is started cranially and caudally, and the sutures are tied at the end of the continuous
thread with self-locking knots. 4 times as much suture material as the length of the wound
must be consumed.
The fascia closure after VAC-treatment can be according to the Israelssons principle as
described below or upon the surgeon's discretion. A staged closure may start distally,
proximally, or in a combination.
Postoperative course
Immediately after index operation, the surgeon fills out the baseline form containing patient
characteristics and comorbidities, etiology of the peritonitis, surgical procedure, and the
complexity of the condition according to Björck's classification. Patients can be transferred
postoperatively to the intensive care unit (ICU) or the ward at the discretion of the
treating team. Upon arrival to either the ward or the ICU, Acute Physiology and Chronic
Health Evaluation II (APACHE II) and sequential organ failure assessment (SOFA) score must be
performed by the attending anesthesiologist. SOFA-scoring and routine blood samples with CRP,
bilirubin, creatinine, and platelets must be performed daily within the first seven days
after index operation. Discharge from the ICU will be at the discretion of the attending
intensivist and surgeon.
After completion of treatment
At hospital discharge, the patients will be booked for follow-up after 12 months in the
outpatient clinic for abdominal palpation and abdominal CT-scan with intravenous contrast and
Valsalva maneuver. In addition, the SF-36 questionnaire will be completed at 3- and 12-months
follow-up.
Power calculation
With an expected peritonitis related complications rate of 40% in the ROD group and 25% in
the VAC group, the desired power of 80%, a significance level of 0.05, and an expected
drop-out of 5% a total of 340 patients should be included. With this sample size a 0.32
standard deviation difference in mean CCI between the two groups could be detected with 80%
as well.
To ensure sufficient recruitment, the study will be multicentre and European. Eight active
centers have been included, and two are in process. Randomization tools along with
eligibility criteria are accessible through our website. The workflow and relevant contact
details appear on posters at the participating departments. Study progress will be available
on the website.
Statistical analysis
Patient characteristics will be summarized with frequencies and proportions (for categorical
variables) or with mean values ± standard deviation, median values, quartiles, and minimum
and maximum values (for numerical variables). Categorical variables will be compared using a
Fisher's exact test and continuous variables with a Wilcoxon rank-sum test.
The primary peritonitis-related complication outcome will be compared between intervention
groups by chi-squared test, reported as relative risk with 95% CI. The CCI outcome will be
compared by linear regression with bootstrapped standard errors reporting mean difference
with 95% confidence intervals.
A superiority and a non-inferiority analysis VAC treatment against primary closure with ROD
will be performed. Applying non-inferiority margin of 5% of the peritonitis related
complications.
An univariate analysis will be performed on the individual complication types (abscess,
leakage, etc.) and complications as a whole (peritonitis related complications and CCI).
Fisher's exact or chi-square test will be used to compare the treatments depending on the
number of observations.
Adjusted analysis by logistic regression will be performed for complications as a whole and
for the individual complications as an outcome, where it will be adjusted for age,
performance status, and comorbidity. The above analyses will also be performed as a subgroup
analysis where patients with APACHE-II score> ten will be included. This evaluates VAC and
ROD in the most seriously ill part of the patient population.
The hospital health care utility and average treatment costs are compared between the
treatment groups. The resource use will be reported as the mean difference with 95%
confidence intervals (CI) compared by linear regression. In case of deviations from normality
assumptions, bootstrapping with 1000 repetitions will be performed. Finally, the proportion
of patients who experience radiological, acute operations will be compared by binomial
regression estimating relative risk (RR) with 95% CI.
The interim analysis will be performed at 25%, 50%, and 75% of recruited patients on the
primary outcome after 30-days to detect significant differences between groups at the
earliest possible time, ultimately leading to the termination of the study. We have adjusted
our power calculation to the interim analyses using the O'Brian-Flemming method. The study
group will have access to the results of the interim analyses and may make the final decision
to terminate the study.
All of the above analyses will be performed as both intention-to-treat (patients will be
analyzed according to their randomization group) and per-protocol analysis (what actually
happened). The main analyses will be performed as complete case analyses. Multiple
imputations will impute missing values in a supplementary analysis, including baseline
characteristics as predictors.
P values less than 0.05 will be considered statistically significant. Statistical
calculations will be performed using Stata software (version 15, Stata Corp LP, Texas, USA).
Ethics
The study will be conducted in accordance with the Declaration of Helsinki and complies with
current GDPR recommendations. The regional Danish Medical Ethics committee has approved the
study to include patients in the acute setting with temporary consent by a surgical equipoise
followed by patient information and consent after recovery. The surgical equipoise must not
have any personal interest in the experiment, have experience, or have knowledge about the
disease and the risks and benefits of the treatments and be indifferent to the therapeutic
value of the two interventions. The rationale for choosing this inclusion model was that the
subjects require immediate surgical intervention, are partly or entirely incapable of
receiving and understanding the information. The severity of the condition does not allow
time for third-party authorization. Both treatment regimens are accepted, safe, and widely
used for this patient group. After the convalescence, patients will be informed about the
project, and consent will be obtained. In instances where the patients do not survive before
regaining habitual state, surrogate consent will be obtained. The patient can withdraw from
the experiment at any time without having to explain him- or herself.
Patients in Denmark are covered by national insurance (Patienterstatningen), international
centers will use country-specific insurance regulations. The study is investigator-initiated
without economic interest to manufacturers or others involved in the investigation. No
financial resources will be provided to the trial participants. Participating centers will
receive the amount of 4000 Danish Krone per included patient yearly to cover the CT-scan of
the abdomen and follow-up at the outpatient clinic.
The final data set will be available to the project owner and data assessor. Data can be
shared in an anonymized form after an approved agreement on request. The primary investigator
is responsible for data collection and handling. Unexpected adverse events must be reported
to the regional committee of ethics.
