Peritoneal Vacuum Therapy to Reduce Inflammatory Response From Abdominal Sepsis/Injury (SAD)

• ClinicalTrials.gov Identifier: NCT01355094
• Recruitment Status: Active, not recruiting
• First Posted: May 17, 2011
• Last Update Posted: November 3, 2020
• Sponsor: University of Calgary
• Collaborators: KCI USA, Inc.; Alberta Health Services
• Information provided by (Responsible Party): Andrew W Kirkpatrick, University of Calgary

Study Description

Brief Summary:

This pilot study will evaluate the effectiveness in actively removing the peritoneal fluid through the use of a commercial suction device compared to passive drainage of the same peritoneal fluid drained through standard surgical drains under bulb suction only, in critically ill patients who require an "open abdomen". Both techniques being used, the commercial KCI AbThera™ device and home made "Stampede" VAC system, are currently approved for use in Canada and used in our facility.

The use or non-use of the open abdomen and its relationship to intra-abdominal hypertension (IAH) and the abdominal compartment syndrome (ACS), the level of IAH must be treated and if so how should be treated - remain controversial. The ultimate treatment for IAH/ACS is to leave the abdominal fascia open after laparotomy, utilizing some form of temporary abdominal closure (TAC) techniques, resulting in an "open abdomen"(OA). The decision to accept an OA can only be made in the operating room and is typically made quite arbitrarily (there is no current standard or protocol),and the TAC used is based on the surgeon's best judgment. The study intends to randomize patients after it has been decided that a TAC is required, which will be applied in the operating room while the patient is fully anesthetized. The only intervention required is to obtain small aliquots (a teaspoonful-15ml) of blood for the evaluation of inflammatory mediators levels, as well as the same volume of intra-peritoneal fluid-that is typically discarded in patients with OA.

Condition or disease	Intervention/treatment	Phase
Abdominal Compartment Syndrome; Intra-abdominal Hypertension	Device: KCI AbThera; Device: "Stampede" VAC	Not Applicable

Detailed Description:

Excessive pressure within the peritoneal cavity, known as intra-abdominal hypertension (IAH), can adversely affect not only intra-peritoneal organ function, but also other organ systems throughout the body. When IAH > 20 mmHg induces new organ dysfunction, a potentially lethal condition known as the abdominal compartment syndrome (ACS) is defined. Practically, this syndrome can be considered multi-system organ failure occurring from severe IAH. While the physical effects of IAH/ACS are increasingly being described, the humoral ones, related to IAH-induced ischemia are poorly understood. Recent animal work suggests that aggressively removing intra-peritoneal fluids, assumed to be vasoactive mediator-rich, leads to better systemic outcomes. There is no human data to support this however. Previous attempts at peritoneal drainage in inflammatory conditions such as sepsis and pancreatitis where not conclusive, but this may have been due to the inefficiency of the systems used and the lack of attention to IAH. Recently, efficient systems providing a temporary abdominal closure (TAC) to both drain intra-peritoneal fluids and to control IAH have been introduced. One of these dressing systems, known as the KCI AbThera™ Abdominal Dressing is currently approved for use in Canada as a temporary abdominal closure (TAC) device but its role in ameliorating systemic sepsis/SIRS has not been evaluated.

We propose a randomized trial of using either the "home Calgary Stampede Vac" involving wall suction or the KCI AbThera™ Abdominal Dressing, to dress the abdomen whenever the operative surgeon determines that an open abdomen is warranted to treat the patient.

In general, others have hypothesized that cytokines, especially peritoneal levels, are sensitive indicators of the post-operative inflammatory reaction and may predict complications. In experimental models IL-6 levels are higher in non-survivors. Further, previous work has noted that the blood level of IL-6, which has a longer half life than TNF-α or IL-1β, is a good index of the overall cytokine cascade activation. Thus the main outcomes to be compared will be between mean cytokine levels measured in each of the two treatment groups - to determine if the KCI AbThera™ Abdominal Dressing can significantly reduce the blood concentration of IL-6 when compared with the "Stampede VAC" system. We are hoping to better understand how the body responds to the inflammatory process that naturally occurs during and after an episode of intra-abdominal hypertension, to identify signals or markers of inflammation and infection as well as its progression and outcome.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Peritoneal Vacuum Therapy to Reduce the Systemic Inflammatory Insult From Intraperitoneal Sepsis/Injury/Hypertension: A Randomized Comparison of Baseline Wall Suction Versus the KCI AbThera™ Abdominal Dressing
• Study Start Date: June 2011
• Estimated Primary Completion Date: June 2022
• Estimated Study Completion Date: June 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: "Stampede" VAC; Calgary-home-made "Stampede" VAC system with only closed drain bulb suction	Device: "Stampede" VAC; The time that the dressing will be left in place will be left to the discretion of the attending surgeon, but revised practice guidelines mandate either formal abdominal closure or dressing change at 24-96 hours from placement. Upon the first OA dressing change, the surgeon is free to utilize whatever temporary closure they choose. Just prior to placement of the dressing, 16 ml (1 table spoon) of blood will be drawn from an existing arterial or venous line (this will qualify as Day 1). The same quantity of blood will be drawn on days 2, 3, 7 and 28 (or hospital discharge, whichever comes first). 15ml of peritoneal fluid will also be collected from the abdomen on the same days or until closure of the abdomen and removal of the dressing.
Experimental: KCI AbThera; commercial AbThera vacuum assisted abdominal closure at 125 mmHg suction	Device: KCI AbThera; The time that the dressing will be left in place will be left to the discretion of the attending surgeon, but revised practice guidelines mandate either formal abdominal closure or dressing change at 24-96 hours from placement. Upon the first OA dressing change, the surgeon is free to utilize whatever temporary closure they choose. Just prior to placement of the dressing, 16 ml (1 table spoon) of blood will be drawn from an existing arterial or venous line (this will qualify as Day 1). The same quantity of blood will be drawn on days 2, 3, 7 and 28 (or hospital discharge, whichever comes first). 15ml of peritoneal fluid will also be collected from the abdomen on the same days or until closure of the abdomen and removal of the dressing.

Outcome Measures

Primary Outcome Measures :

1. Systemic inflammatory marker levels and peritoneal fluid inflammatory marker levels [ Time Frame: admission to dicharge, expected average of hospital stay 4 weeks. ]
   Intra-peritoneal and plasma inflammatory mediators will be measured on a treatment allocation basis immediately after initiation of the TAC, and thereafter at 2, 3, 7 and 28 days. The mediators studied will include, but are not limited to TNF-α, IL-1β, IL-6, IL-10, IL-12, and CRP.

Secondary Outcome Measures :

1. Physiological Outcomes [ Time Frame: admission to hospital discharge; expected average of hospital stay 4 weeks. ]
   Determination of the type and activation status of inflammatory cells present in the peritoneal fluid, Measurement of the activation potential of peritoneal fluid, Peritoneal fluid drainage volume, Post-operative fluid balance, Mean 24 hour intra-abdominal pressure (IAP), daily WSACS IAH grading classification, APACHE II score, SOFA score, PaO2/FiO2 ratio, Oxygenation Index, Vasopressor Requirements,RIFLE score, Need for renal replacement therapy, Mean 24 hour lactate level, Mean 24 hour enteral tolerance (if no anastomosis)
2. Global Outcomes [ Time Frame: patients will be followed-up for 6 months ]
   Death, days with fascial closure for the month after admission, ventilator free days for the month after admission, ICU free days from the month after admission, days free of renal replacement therapy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Critically ill/injured requiring intensive care unit admission
• Decision regarding the need to utilize an open abdomen technique after the first laparotomy
• Age > 18
• Non-pregnant

Exclusion Criteria:

• Decision to formally close the abdomen after the initial laparotomy
• Patients receiving intra-peritoneal chemotherapy
• Pregnancy
• Age < 18

Contacts and Locations

Locations

Canada, Alberta

Foothills Medical Centre

Calgary, Alberta, Canada, T2N 2T9

Sponsors and Collaborators

University of Calgary

KCI USA, Inc.

Alberta Health Services

Investigators

• Principal Investigator: Andrew W Kirkpatrick, MD; Canadian Trauma Trials Collaborative

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Björck M, Kirkpatrick AW, Cheatham M, Kaplan M, Leppäniemi A, De Waele JJ. Amended Classification of the Open Abdomen. Scand J Surg. 2016 Mar;105(1):5-10. doi: 10.1177/1457496916631853. Epub 2016 Feb 29.

Kirkpatrick AW, Roberts DJ, Faris PD, Ball CG, Kubes P, Tiruta C, Xiao Z, Holodinsky JK, McBeth PB, Doig CJ, Jenne CN. Active Negative Pressure Peritoneal Therapy After Abbreviated Laparotomy: The Intraperitoneal Vacuum Randomized Controlled Trial. Ann Surg. 2015 Jul;262(1):38-46. doi: 10.1097/SLA.0000000000001095.

Roberts DJ, Jenne CN, Ball CG, Tiruta C, Léger C, Xiao Z, Faris PD, McBeth PB, Doig CJ, Skinner CR, Ruddell SG, Kubes P, Kirkpatrick AW. Efficacy and safety of active negative pressure peritoneal therapy for reducing the systemic inflammatory response after damage control laparotomy (the Intra-peritoneal Vacuum Trial): study protocol for a randomized controlled trial. Trials. 2013 May 16;14:141. doi: 10.1186/1745-6215-14-141.

• Responsible Party: Andrew W Kirkpatrick, Medical Director, Trauma Services, CD, MD, FACS, FRCSC, MHSc, University of Calgary
• ClinicalTrials.gov Identifier: NCT01355094
• Other Study ID Numbers: E-23706
• First Posted: May 17, 2011
• Last Update Posted: November 3, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No plan

Keywords provided by Andrew W Kirkpatrick, University of Calgary:

temporary abdomen closure; peritoneal vacuum therapy; open abdomen; abdominal compartment syndrome; intra-abdominal sepsis; intra-abdominal hypertension; critical care

Additional relevant MeSH terms:

Sepsis; Compartment Syndromes; Intra-Abdominal Hypertension; Hypertension; Pathologic Processes; Vascular Diseases; Cardiovascular Diseases; Infection; Systemic Inflammatory Response Syndrome; Inflammation; Muscular Diseases; Musculoskeletal Diseases