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Closed or Open Abdomen for the Management of Abdominal Sepsis

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ClinicalTrials.gov Identifier: NCT03163095
Recruitment Status : Recruiting
First Posted : May 22, 2017
Last Update Posted : February 3, 2023
Sponsor:
Collaborator:
Alberta Health services
Information provided by (Responsible Party):
Andrew W Kirkpatrick, University of Calgary

Tracking Information
First Submitted Date  ICMJE May 18, 2017
First Posted Date  ICMJE May 22, 2017
Last Update Posted Date February 3, 2023
Actual Study Start Date  ICMJE June 2, 2019
Estimated Primary Completion Date July 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2018)		 The numbers of participants who are survival in hospital stay [ Time Frame: 90 days after participants enrolled in the study ]
The rate of survival of participants in both arms
Original Primary Outcome Measures  ICMJE
 (submitted: May 19, 2017)		 The numbers of participants who are survival in hospital stay [ Time Frame: 30 days after participants enrolled in the study ]
The rate of survival of participants in both arms
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2017)
  • The days of intensive care unit stay [ Time Frame: 30 days after participants enrolled in the study ]
    The median length of days in ICU needed by participants in both arms
  • The pg/ml of blood Interleukin-6 [ Time Frame: 72 hours after participants enrolled in the study ]
    The mean concentrations of blood IL-6 in participants in both arms
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Closed or Open Abdomen for the Management of Abdominal Sepsis
Official Title  ICMJE Closed Versus Open Abdomen in the Surgical Treatment of Severe Secondary Peritonitis: a Randomized Controlled Clinical Trial
Brief Summary

This is a prospective randomized clinical study. The study will comprise the randomized decision to either A) primarily close the fascia after laparotomy for intra-abdominal infection (CLOSED); or B) leave the fascia open after laparotomy and apply a temporary abdominal closure (TAC) device (OPEN) with a vacuum drain.

Although debatable, both procedures (CLOSED or OPEN abdomen) are acceptable based on current suggested standard of care. Thus, high quality data to direct clinical decision making in this highly lethal condition is urgently required.
Detailed Description

Severe complicated intra-abdominal sepsis (SCIAS) is a World-Wide challenge, with high mortality rates, and ever increasing incidence. Most cases are subjected to secondary peritonitis in which there is a physical disruption of the integrity of the gastrointestinal (GI) tract leading to contamination of the peritoneal cavity. Ultimately, the resultant organ damage results in auto-amplifying biomediator generation and systemic inflammation. Mortality rates range from 10% to over 40% when shock is present. The key principles of treating SIAS are early antibiotic administration and the earliest possible operative intervention to provide source control of GI perforations/disruptions. A further potential therapeutic option may be to utilize open abdomen (OA) management with active negative peritoneal pressure therapy (ANPPT) to remove intra-peritoneal inflammatory ascites and to ameliorate the systemic damage from SCIAS. Recent data from a randomized controlled trial including either severe peritonitis or trauma patients, showed the 30-days mortality differed between commercial open abdomen systems and non-commercial technique, which favored the more effective commercial device. Although there is a biologic rationale for such an intervention from animal models as well as non-standardized clinical utilization currently, the open abdomen management with ANPPT remains a novel therapy with much clinical equipoise. Thus, the Closed Or Open after Laparotomy (COOL) study will constitute a prospective randomized controlled trial to address this issue.

There is a complex relationship between pressure, ischemia, and inflammation within the peritoneal cavity. Independently the damaged gut seems to act as a continued source of inflammation propagating systemic inflammatory response syndrome (SIRS) and potentiating multi-organ dysfunction syndrome (MODS). Although extremely complicated, visceral ischemia further generates multiple immunological mediators with the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6), as well as inhibitive cytokines such as interleukin 10 (IL-10). Post-operative complications associate with increasing levels of systemic IL-6, and peritoneal TNF-α. Jansson and colleagues believe that peritoneal cytokines in humans respond more extensively compared to systemic cytokines, and that a normal postoperative course is characterized by decreasing levels of peritoneal cytokines based on studies of both elective and emergency surgery. Overall, the peritoneal cytokine response is much higher than the systemic response in peritonitis.

ANPPT therapy may be a more direct and focused solution to this complicated problem, and that will be complementary to the other benefits of open abdomen management in the sickest patients. Whether improved post-operative courses can be obtained through this relatively simple approach of actively removing peritoneal cytokines in humans is therefore a secondary objective of this trial.

Another potential benefit of ANPPT after severe infection may be the attendant decompression of the abdominal compartment and prevention of even modest degrees of intra-abdominal hypertension (IAH). Patients with intra-abdominal infections are at risk of elevated intra-abdominal pressure (IAP) both as a result of the primary intra-peritoneal disease, and as large fluid resuscitation often required maintaining organ perfusion. Recent studies have demonstrated a high prevalence of IAH following aggressive resuscitation of septic patients. Intra-abdominal hypertension is present in as many as 80% of septic medical and surgical ICU patients. Reintam also reported that septic patients with IAH had a 50% rate of mortality compared to 19% without IAH, making IAH a significant marker for an increased risk of death. Within our own institution, rates of IAH were over 87% of septic ICU patients and further 61% of these patients had severe IAH at levels commensurate with abdominal compartment syndrome (ACS). Although direct translation to humans is uncertain, even modest degrees of IAH (often clinically ignored) have been found to have profound effects on propagating multiple organ failure in animals with ischemia/intra-peritoneal infections.

The study intervention will comprise the randomized decision to either A) primarily close the fascia after laparotomy for SCIAS (CLOSED); or B) leave the fascia open after laparotomy for SCIAS and apply an ANPPT temporary abdominal closure (TAC) device (OPEN).

Patients will be randomized intra-operatively once it is determined that COMPLICATED and SEVERE Intra-Abdominal Infection (SCIAS) is present. SEVERE will be defined and denoted by the presence of any organ dysfunction exemplified by septic shock OR a Predisposition-Infection-Response-Organ Dysfunction Score > 3 or a World-Society-of-Emergency-Surgery-Sepsis-Severity-Score > 8, and COMPLICATED with the presence of purulent, feculent, or enteric spillage over at least 2 intra-peritoneal quadrants.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomization by blocks on a website.
Masking: Single (Outcomes Assessor)
Masking Description:
Research members in the laboratory will be blinded with participants' clinical data.
Primary Purpose: Treatment
Condition  ICMJE
  • Abdominal Sepsis
  • Abdominal Infection
Intervention  ICMJE
  • Device: Open Abdomen Management with ANPPT dressing

    The abdominal fascia will not be closed, but a temporally abdominal closure (TAC) dressing, such as AbThera dressing, will be placed to protect the viscera with active Negative Pressure Peritoneal Therapy.

    The time that the TAC dressing will be changed will be left to the discretion of the attending surgeon, but practice guidelines mandate either formal abdominal closure or dressing change at 24-72 hours from placement.

    Blood samples and peritoneal fluid will be drawn up to 72 hours after enrollment.

  • Other: Closed Abdomen Management

    Primary closure of the abdominal fascia with placement of an intra-peritoneal drain (such as a Jackson-Pratt drain).

    This strategy will allow drainage of intra-peritoneal fluid for both clinical reasons and to facilitate intra-peritoneal fluid testing. Closure or not of the skin will be left to the attending surgeons discretion. Any decision to perform a relaparotomy (Relaparotomy on Demand) will be at the discretion of the treating critical care teams, and in no way mandated by this recruitment.

    Blood samples and peritoneal fluid (if available) will be drawn up to 72 hours after enrollment.
Study Arms  ICMJE
  • Active Comparator: Open Abdomen Management with ANPPT dressing
    The abdominal fascia will not be closed, but a temporally abdomenal closure (TAC) dressing (such as AbThera dressing) will be placed to protect the viscera with active Negative Pressure Peritoneal drain. Formal abdominal closure or dressing change at 24-72 hours from placement should be performed.
    Intervention: Device: Open Abdomen Management with ANPPT dressing
  • Sham Comparator: Closed Abdomen Management
    Primary closure of the abdominal fascia with placement of an intra-peritoneal drain (such as a Jackson-Pratt drain). Any decision to perform a re-laparotomy will be at the discretion of the treating surgical team.
    Intervention: Other: Closed Abdomen Management
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 10, 2018)		 550
Original Estimated Enrollment  ICMJE
 (submitted: May 19, 2017)		 300
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date July 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Presence of purulent, feculent, or enteric spillage over at least 2 intra-peritoneal quadrants intra-operatively;
  • Septic shock, or
  • Predisposition-Infection-Response-Organ Dysfunction Score > 3, or
  • World-Society-of-Emergency-Surgery-Sepsis-Severity-Score > 8

Exclusion Criteria:

  • Pregnant;
  • Confirmed or strongly suspected severe IAH (IAP>20 mmHg);
  • No intentional of providing ongoing care;
  • pancreatitis as the source of peritonitis;
  • uncontrolled bleeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Andrew Kirkpatrick, MD 403-944-2888 andrew.kirkpatrick@ahs.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03163095
Other Study ID Numbers  ICMJE REB16-1588-the COOL study
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Not shared.
Current Responsible Party Andrew W Kirkpatrick, University of Calgary
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Calgary
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Alberta Health services
Investigators  ICMJE
Principal Investigator: Andrew W Kirkpatrick, MD University of Calgary
PRS Account University of Calgary
Verification Date February 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP