Ignite Creation Date:
2025-12-24 @ 2:00 PM
Ignite Modification Date:
2026-02-24 @ 2:29 PM
Study NCT ID:
NCT03163095
Status:
RECRUITING
Last Update Posted:
2023-02-03
First Post:
2017-05-18
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Closed or Open Abdomen for the Management of Abdominal Sepsis
Sponsor:
University of Calgary
Organization:
Study Overview
Official Title:
Closed Versus Open Abdomen in the Surgical Treatment of Severe Secondary Peritonitis: a Randomized Controlled Clinical Trial
Status:
RECRUITING
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: