Preoperative High-dose Dexamethasone and Emergency Laparotomy

NCT04791566 | Completed Phase 4 DMC

• 1 other identifier: H-20038432
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Intestinal Obstruction and Ileus; Perforated Viscus; Sepsis; Pathophysiology; Inflammatory Response

Outcome Measures

Primary Outcomes (1)

• plasma C-reactive protein

  24* hours (*+/- 6 hours) after surgery.

Secondary Outcomes (1)

• changes in plasma C-reactive protein

  Preoperatively, 6 hours postoperatively, as well as postoperative day 3 and 5

Other Outcomes (20)

• changes in postoperative inflammatory responses (IL-6, TNF alfa)

  Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5

• Change in plasma Syndecain-1sE-Selectin (CD62E)

  Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5

• Change in plasma soluble thrombomodulin (sTM)(CD141)

  Preoperatively, 6 hours postoperatively, as well as postoperative day 1,3 and 5

Study Arms (4)

Intestinal obstruction, Dexamethasone 1 mg/kg

ACTIVE COMPARATOR

Dexamethasone 1 mg/kg administered preoperatively as an i.v. infusion over 10-15 minutes

Drug: Dexamethasone 1 mg/kg

Intestinal obstruction, PLACEBO

PLACEBO COMPARATOR

Physiologic saline, administered preoperatively as an i.v. infusion over 10-15 minutes

Drug: Physiologic saline

Perforated viscus, Dexamethasone 1 mg/kg

ACTIVE COMPARATOR

Dexamethasone 1 mg/kg administered preoperatively as an i.v. infusion over 10-15 minutes

Drug: Dexamethasone 1 mg/kg

Perforated viscus, PLACEBO

PLACEBO COMPARATOR

Physiologic saline, administered preoperatively as an i.v. infusion over 10-15 minutes

Drug: Physiologic saline

Interventions

Dexamethasone 1 mg/kg DRUG

Dexamethasone 1 mg/kg administered as a single preoperative i.v. infusion over 10-15 min prior to general anaesthesia

Also known as: Dexa-ratiopharm

Intestinal obstruction, Dexamethasone 1 mg/kg; Perforated viscus, Dexamethasone 1 mg/kg

Physiologic saline DRUG

100 mL Physiologic saline administered as a single preoperative i.v., infusion over 10-15 min prior to general anaesthesia

Intestinal obstruction, PLACEBO; Perforated viscus, PLACEBO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mirjana Cihoric: lead

Study Sites (1)

Mirjana Cihoric

Hvidovre, 2650, Denmark

Location

Related Publications (1)

• Cihoric M, Kehlet H, Lauritsen ML, Hojlund J, Kanstrup K, Karnsund S, Foss NB. Preoperative high dose of dexamethasone in emergency laparotomy: randomized clinical trial. Br J Surg. 2024 Jul 2;111(7):znae130. doi: 10.1093/bjs/znae130.

  PMID: 39028763 DERIVED

MeSH Terms

Conditions

Intestinal Obstruction; Ileus; Sepsis

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Nicolai Bang Foss, Professor

  Dept. of Anaesthesiology and Intensive Care

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Research fellow

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: March 10, 2021
• Study Start: March 1, 2021
• Primary Completion: October 9, 2022
• Study Completion: December 9, 2022
• Last Updated: December 14, 2022

Record last verified: 2022-12

Locations

DK (1)