Back to resultsPreoperative High-dose Dexamethasone and Emergency Laparotomy
Primary Purpose
Intestinal Obstruction and Ileus, Perforated Viscus, Sepsis
Status
Completed
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Dexamethasone 1 mg/kg
Physiologic saline
Sponsored by
About this trial
This is an interventional treatment trial for Intestinal Obstruction and Ileus
Eligibility Criteria
Inclusion Criteria:
Adults (18 years or over) undergoing emergency laparotomy (laparotomy or laparoscopy) for following abdominal pathology:
- Primary perforated viscus (perforated ulcer, small intestine or colon)
- Primary intestinal obstruction ( small intestine or colon)
- Provided verbal and written informed consent
- Must speak and understand the Danish language
Exclusion Criteria:
- Appendectomies, cholecystectomies, negative diagnostic laparoscopies/laparotomies, herniotomies without bowel resections, sub-acute internal hernias after gastric bypass surgery, sub-acute surgery for inflammatory bowel diseases.
- Emergency re-operations after elective surgery owing to paralytic/obstructive ileus, perforated viscus, anastomotic leakage
- Reoperation owing to fascial separation with no other abdominal pathology identified and sub-acute colorectal cancer-surgery will be excluded from the cohort. Sub-acute surgery is defined as surgery planned within 48 hours.
- Intestinal Ischemia
- intraabdominal bleeding
- Traumas, gynecological, urogenital and other vascular pathology, pregnant participants.
- Dementia and/or cognitive dysfunction (diagnosed).
- Participants not oriented in time, place and person
- Insuline treatment for diabetes mellitus type I and II
- Current treatment with systemic glucocorticoids or immune suppressive treatment ( apart from inhalation steroids)
Allergies to trial medicine
-
Sites / Locations
- Mirjana Cihoric
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Placebo Comparator
Active Comparator
Placebo Comparator
Arm Label
Intestinal obstruction, Dexamethasone 1 mg/kg
Intestinal obstruction, PLACEBO
Perforated viscus, Dexamethasone 1 mg/kg
Perforated viscus, PLACEBO
Arm Description
Dexamethasone 1 mg/kg administered preoperatively as an i.v. infusion over 10-15 minutes
Physiologic saline, administered preoperatively as an i.v. infusion over 10-15 minutes
Dexamethasone 1 mg/kg administered preoperatively as an i.v. infusion over 10-15 minutes
Physiologic saline, administered preoperatively as an i.v. infusion over 10-15 minutes
Outcomes
Primary Outcome Measures
plasma C-reactive protein
Secondary Outcome Measures
changes in plasma C-reactive protein
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04791566
Brief Title
Preoperative High-dose Dexamethasone and Emergency Laparotomy
Official Title
The Effects of Preoperative High-dose Dexamethasone on Inflammatory Response and Recovery After Emergency Laparotomy, a Randomized, Double-blind, Placebo-controlled Clinical Trial - AHA STEROID TRIAL
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
October 9, 2022 (Actual)
Study Completion Date
December 9, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Mirjana Cihoric
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The aim of this trial is to evaluate the effect of high-dose glucocorticoid on inflammatory response and recovery after emergency laparotomy in participants with intestinal obstruction and perforated viscus.
Primary outcome is the reduction of C-reactive protein on postoperative day 1. Secondary outcomes are organ specific complications in the post anaesthesia phase, endothel and inflammatory markers, fluid status, preload dependency, pain, lung function, nausea and mobilization during the first 5 days after surgery, .
The investigators hypothesize, that a preoperative single high dose of glucocorticoid reduces systemic inflammatory response after emergency laparotomy.
Detailed Description
Surgical trauma and accompanying inflammation results in increased capillary permeability leading to tissue edema. Since the vascular endothelium contributes to homeostasis, endothelial damage may increase the risk of cardiovascular and hemodynamic complications.
Pre-operative high-dose glucocorticoids provide reduction in the inflammatory response after surgery, effective pain relief in several major surgical procedures, as well as reducing fatigue, impairing endothelial dysfunction, potentially amend fluid extravasation, edema and dyscoagulation and vasodilation.
However, glucocorticoids have not been assessed in patients with peritonitis or intestinal obstruction, specifically, the impact on pain, fluid dynamics, respiratory as well as endothelial function and mobilization in both obstruction and perforation.
In this study, patients will be randomized to either high dose dexamethason (1 mg /kg) or placebo (0,9% NaCl), administered as a single dose preoperatively. The investigatoris hypothesize that a preoperative single high dose of glucocorticoid reduces systemic inflammatory response after emergency laparotomy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intestinal Obstruction and Ileus, Perforated Viscus, Sepsis, Pathophysiology, Inflammatory Response
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intestinal obstruction, Dexamethasone 1 mg/kg
Arm Type
Active Comparator
Arm Description
Dexamethasone 1 mg/kg administered preoperatively as an i.v. infusion over 10-15 minutes
Arm Title
Intestinal obstruction, PLACEBO
Arm Type
Placebo Comparator
Arm Description
Physiologic saline, administered preoperatively as an i.v. infusion over 10-15 minutes
Arm Title
Perforated viscus, Dexamethasone 1 mg/kg
Arm Type
Active Comparator
Arm Description
Dexamethasone 1 mg/kg administered preoperatively as an i.v. infusion over 10-15 minutes
Arm Title
Perforated viscus, PLACEBO
Arm Type
Placebo Comparator
Arm Description
Physiologic saline, administered preoperatively as an i.v. infusion over 10-15 minutes
Intervention Type
Drug
Intervention Name(s)
Dexamethasone 1 mg/kg
Other Intervention Name(s)
Dexa-ratiopharm
Intervention Description
Dexamethasone 1 mg/kg administered as a single preoperative i.v. infusion over 10-15 min prior to general anaesthesia
Intervention Type
Drug
Intervention Name(s)
Physiologic saline
Intervention Description
100 mL Physiologic saline administered as a single preoperative i.v., infusion over 10-15 min prior to general anaesthesia
Primary Outcome Measure Information:
Title
plasma C-reactive protein
Time Frame
24* hours (*+/- 6 hours) after surgery.
Secondary Outcome Measure Information:
Title
changes in plasma C-reactive protein
Time Frame
Preoperatively, 6 hours postoperatively, as well as postoperative day 3 and 5
Other Pre-specified Outcome Measures:
Title
changes in postoperative inflammatory responses (IL-6, TNF alfa)
Time Frame
Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Title
Change in plasma Syndecain-1sE-Selectin (CD62E)
Time Frame
Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Title
Change in plasma soluble thrombomodulin (sTM)(CD141)
Time Frame
Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Title
Change in plasma sE-Selectin (CD62E)
Time Frame
Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Title
Change in vascular endothelial growth factor (VEGF)
Description
0 to 1 point: Not high risk; 2 to 3 points: High risk
Time Frame
Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Title
quick Sequential Organ Failure Assessment score, qSOFA
Time Frame
Assessed once preoperatively and 4 times daily during the first 5 postoperative days
Title
Preload dependency via stroke volume(SV) guided resuscitation
Time Frame
Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Title
Fluid distribution, full body water via bioelectrical impedance vector analysis
Time Frame
Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5
Title
Peak flow measurements
Time Frame
Once a day on postoperative day 1,3 and 5
Title
Postoperative need for antiemetic and analgesic beyond standard course
Time Frame
Once a day during the the first 5 postoperative days
Title
Mobilization, The Cumulated Ambulation Score (CAS)
Description
The CAS describes the patient's independence with regard to three activities (getting in and out of bed, sit-to-stand-to-sit from a chair, and walking). Each activity is assessed on a three-point ordinal scale from 0-2 (0 = Not able to, despite human assistance and verbal cueing, 1 = Able to, with human assistance and/or verbal cueing from one or more persons, 2 = Able to safely, without human assistance or verbal cueing, use of a walking aid allowed) resulting in a total daily CAS score ranging from zero to six
Time Frame
Once a day on postoperative day 1,3 and 5
Title
Postoperative delirium via Confusion Assessment method scale
Description
1.a: Acute onset
1b: Fluctuating course, 2: inattention 3: disorganized thinking 4: altered level of conciosness At least one criterion must be met for a positive result
Time Frame
Once a day during the the first 5 postoperative days
Title
Postoperative resting pain measured according to Numeric Rating Scale (NRS)
Description
0-10 where 0 is no pain and 10 is the worst pain imaginable
Time Frame
6 hours after surgery as well as once a day one postoperative day 1,3 and 5
Title
Postoperative pain during mobilization, measured according to Numeric Rating Scale (NRS)
Description
0-10 where 0 is no pain and 10 is the worst pain imaginable
Time Frame
6 hours after surgery as well as once one postoperative day 1,3 and 5
Title
30-day postoperative mortality
Time Frame
30 days
Title
90-day postoperative mortality
Time Frame
90 days
Title
30-day postoperative complications
Time Frame
30 days
Title
Length of ICU stay
Time Frame
30 days
Title
Overall hospital stay
Time Frame
30 days
Title
Plasma NO-bioavailability (L-arginine, asymmetric dimethylarginine)
Time Frame
preoperatively, 6 hours after surgery as well as once one postoperative day 1,3 and 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adults (18 years or over) undergoing emergency laparotomy (laparotomy or laparoscopy) for following abdominal pathology:
Primary perforated viscus (perforated ulcer, small intestine or colon)
Primary intestinal obstruction ( small intestine or colon)
Provided verbal and written informed consent
Must speak and understand the Danish language
Exclusion Criteria:
Appendectomies, cholecystectomies, negative diagnostic laparoscopies/laparotomies, herniotomies without bowel resections, sub-acute internal hernias after gastric bypass surgery, sub-acute surgery for inflammatory bowel diseases.
Emergency re-operations after elective surgery owing to paralytic/obstructive ileus, perforated viscus, anastomotic leakage
Reoperation owing to fascial separation with no other abdominal pathology identified and sub-acute colorectal cancer-surgery will be excluded from the cohort. Sub-acute surgery is defined as surgery planned within 48 hours.
Intestinal Ischemia
intraabdominal bleeding
Traumas, gynecological, urogenital and other vascular pathology, pregnant participants.
Dementia and/or cognitive dysfunction (diagnosed).
Participants not oriented in time, place and person
Insuline treatment for diabetes mellitus type I and II
Current treatment with systemic glucocorticoids or immune suppressive treatment ( apart from inhalation steroids)
Allergies to trial medicine
-
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolai Bang Foss, Professor
Organizational Affiliation
Dept. of Anaesthesiology and Intensive Care
Official's Role
Study Director
Facility Information:
Facility Name
Mirjana Cihoric
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Preoperative High-dose Dexamethasone and Emergency Laparotomy
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