Vacuum Assisted Closure Versus On-demand Relaparotomy in Patients With Fecal or Diffuse Peritonitis

NCT ID: NCT03932461

Last Updated: 2023-11-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

340 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-01

Study Completion Date

2027-09-01

Brief Summary

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Multicenter randomized controlled trial including patients with fecal or diffuse peritonitis to either vacuum assisted closure or relaparotomy "on-demand".

Detailed Description

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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.

Conditions

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Fecal Peritonitis Secondary Peritonitis Diffuse; Peritonitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Multicentre randomized non-blinded clinical trial comprising of \> 4 centres. In total there will be included 320 patients.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Vacuum assisted closure

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. Each dressing change must be performed in the operation theatre with the patient in general anesthesia and muscle relaxation.

Group Type ACTIVE_COMPARATOR

Vacuum assisted closure

Intervention Type PROCEDURE

The Vacuum assisted closure system consists of an abdominal dressing covering the intra abdominal viscera over the dressing there will be placed a blue sponge which will be covered by drape and connected to a vacuum pump.

Relaparotomy "on-demand"

The Isreaelsson principle includes a running suture of the fascia with a distance of 5 mm between the stitches of 5 mm and the distance to the facial edge of 5-10 mm. Monofilament PDS 2-0 or equivalent is used. The suturing is started cranially and caudally, and the sutures are tied with self-locking knots. Four times as much suture material as the length of the wound must be used. The peritoneal fluid must be cultured at closure.

The treating surgeon decides to perform a ROD and should be guided by the patient's general condition, gastrointestinal function, renal function, and inflammatory parameters at daily rounds.

Group Type ACTIVE_COMPARATOR

Relaparotomy "on demand"

Intervention Type PROCEDURE

Abdomen is closed at the index operation after source of peritonitis is treated. Every 48-hours the patients are evaluated for the need of relaparotomy based on clinical and paraclinical parameters.

Interventions

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Vacuum assisted closure

The Vacuum assisted closure system consists of an abdominal dressing covering the intra abdominal viscera over the dressing there will be placed a blue sponge which will be covered by drape and connected to a vacuum pump.

Intervention Type PROCEDURE

Relaparotomy "on demand"

Abdomen is closed at the index operation after source of peritonitis is treated. Every 48-hours the patients are evaluated for the need of relaparotomy based on clinical and paraclinical parameters.

Intervention Type PROCEDURE

Other Intervention Names

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VAC® Abdominal Dressing System, KCI, (San Antonio, TX)

Eligibility Criteria

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Inclusion Criteria

Patients eligible for enrolment are 18+ years of age and are scheduled for acute laparotomy due to suspected peritonitis originating from perforation of the small bowel, colon, or rectum. To be included, purulent, enteric, or fecal contamination in a minimum of 2 out of 4 quadrants must be confirmed.

Exclusion Criteria

* 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
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Odense University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Pooya Rajabaleyan

Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Niels Qvist, Professor

Role: STUDY_DIRECTOR

Surgical Department A, Odense University Hospital, Denmark

Uffe Tange Holst, M.D.

Role: STUDY_CHAIR

Surgical Department A, Odense University Hospital, Denmark

Jens Michelsen, M.D.

Role: STUDY_CHAIR

Anesthesiology department V, Odense University Hospital, Denmark

Palle Toft, Professor

Role: STUDY_CHAIR

Anesthesiology department V, Odense University Hospital, Denmark

Locations

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Odense University Hospital

Odense, Fyn, Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Pooya Rajabaleyan, M.D.

Role: CONTACT

+4527118889

Mark Ellebæk, M.D., Ph.d.

Role: CONTACT

+4540880511

Facility Contacts

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Pooya Rajabaleyan, M.D.

Role: primary

+4527118889

Mark Ellebæk, M.D., Ph.d.

Role: backup

+4540880511

References

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Rajabaleyan P, Michelsen J, Tange Holst U, Moller S, Toft P, Luxhoi J, Buyukuslu M, Bohm AM, Borly L, Sandblom G, Kobborg M, Aagaard Poulsen K, Schou Love U, Ovesen S, Grant Solling C, Morch Sondergaard B, Lund Lomholt M, Ritz Moller D, Qvist N, Bremholm Ellebaek M; VACOR study group. Vacuum-assisted closure versus on-demand relaparotomy in patients with secondary peritonitis-the VACOR trial: protocol for a randomised controlled trial. World J Emerg Surg. 2022 May 26;17(1):25. doi: 10.1186/s13017-022-00427-x.

Reference Type DERIVED
PMID: 35619144 (View on PubMed)

Other Identifiers

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VACOR2019

Identifier Type: -

Identifier Source: org_study_id

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