The Effect of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery on Innate Immune Homeostasis. (RECOVER-PLUS)
Primary Purpose
Pneumoperitoneum, Neuromuscular Blockade, Surgery
Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Low pressure pneumoperitoneum
Rocuronium bromide
Sponsored by
About this trial
This is an interventional treatment trial for Pneumoperitoneum focused on measuring Laparoscopic surgery, Deep neuromuscular block, Low pressure pneumoperitoneum, Postoperative immune suppression
Eligibility Criteria
Inclusion Criteria:
- Scheduled for laparoscopic colorectal surgery with a primary anastomosis
- Obtained informed consent
- Age over 18 years
Exclusion Criteria:
- Insufficient control of the Dutch language to read the patient information and to fill out the questionnaires
- Primary colostomy
- Neo-adjuvant chemotherapy
- Chronic use of analgesics or psychotropic drugs
- Use of NSAIDs shorter than 5 days before surgery
- Known or suspected allergy to rocuronium of sugammadex
- Neuromuscular disease
- Indication for rapid sequence induction
- Severe liver- or renal disease (creatinine clearance <30ml/min)
- BMI >35 kg/m²
- Deficiency of vitamin K dependent clotting factors or coagulopathy
Sites / Locations
- Canisius Wilhelmina Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Low pressure PNP, deep NMB
Normal pressure PNP, moderate NMB
Arm Description
Low pressure pneumoperitoneum of 8 mmHg with deep neuromuscular block (post tetanic count of 1-2) reached by titration with continuous infusion of Rocuronium bromide.
Normal pressure pneumoperitoneum of 12 mmHg with moderate neuromuscular block (TOF count of 1-2) reached by titration with bolus or continuous infusion of a low dose of Rocuronium bromide.
Outcomes
Primary Outcome Measures
Mononuclear cell responsiveness ex vivo
TNFalpha release upon LPS stimulation
Secondary Outcome Measures
Mononuclear cell responsiveness ex-vivo
IL-6, IL-10 and IL-1beta release upon LPS stimulation
Serum DAMPs and cytokines
Danger associated molecular patterns, TNFalpha, IL-6 and IL-10
HLA-DR mRNA expression
MHC-II antigen presenting immune receptor
Peritoneal histology and HIF1alpha expression
Histology and HIF1alpha mRNA expression of a peritoneal biopsy
Full Information
NCT ID
NCT03572413
First Posted
June 18, 2018
Last Updated
October 27, 2021
Sponsor
Radboud University Medical Center
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT03572413
Brief Title
The Effect of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery on Innate Immune Homeostasis.
Acronym
RECOVER-PLUS
Official Title
The Effectiveness of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery in Preserving Innate Immune Homeostasis by Reducing Peritoneal Mesothelial Cell Injury.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
October 24, 2018 (Actual)
Primary Completion Date
August 31, 2020 (Actual)
Study Completion Date
December 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Substudy of the RECOVER trial (a randomised controlled trial comparing the effect of low pressure pneumoperitoneum with deep neuromuscular block versus normal pressure pneumoperitoneum with moderate neuromuscular block during laparoscopic colorectal surgery on early quality of recovery) investigating innate immune homeostasis after laparoscopic colorectal surgery.
Detailed Description
Rationale: increased intra-abdominal pressure can cause peritoneal mesothelial cell injury either directly or by compression of the capillary vessels, causing a variable degree of ischemia reperfusion injury. The immune system can identify damage to host cells by recognising Danger-Associated Molecular Patterns (DAMPs) that are released upon cell death in an uncontrolled fashion, such as during surgical trauma. DAMPs elicit an immune response similar to the response to invading pathogens and induce an anti-inflammatory immune response strongly related to postoperative recovery, infectious complications and mortality. Low pressure PNP is associated with lower levels of serum pro- and anti-inflammatory cytokines and better preservation of innate immune function.
Objective: to establish the relationship between the use of low pressure pneumoperitoneum with deep neuromuscular blockade and innate immune function after laparoscopic colorectal surgery.
Study design: a multi-center, blinded, randomized controlled clinical trial.
Study population: adult individuals scheduled for laparoscopic colorectal surgery with a primary colonic anastomosis.
Intervention: participants will be randomly assigned in a 1:1 fashion to either the experimental group (group A): low pressure PNP (8 mmHg) with deep NMB (PTC 1-2) or the control group (group B): normal pressure PNP (12 mmHg) with moderate NMB (TOF count 1-2).
Primary endpoint: mononuclear cell responsiveness ex-vivo as reflected by TNFα release upon LPS stimulation.
Secondary endpoints: mononuclear cell responsiveness ex-vivo as reflected by IL-6, IL-10 and IL-1beta release upon LPS stimulation. Peritoneal mesothelial hypoxia as reflected by peritoneal HIF1α mRNA expression, histological peritoneal mesothelial cell injury and plasma levels of DAMPs and cytokines.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumoperitoneum, Neuromuscular Blockade, Surgery, Immune Suppression
Keywords
Laparoscopic surgery, Deep neuromuscular block, Low pressure pneumoperitoneum, Postoperative immune suppression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low pressure PNP, deep NMB
Arm Type
Experimental
Arm Description
Low pressure pneumoperitoneum of 8 mmHg with deep neuromuscular block (post tetanic count of 1-2) reached by titration with continuous infusion of Rocuronium bromide.
Arm Title
Normal pressure PNP, moderate NMB
Arm Type
Active Comparator
Arm Description
Normal pressure pneumoperitoneum of 12 mmHg with moderate neuromuscular block (TOF count of 1-2) reached by titration with bolus or continuous infusion of a low dose of Rocuronium bromide.
Intervention Type
Procedure
Intervention Name(s)
Low pressure pneumoperitoneum
Other Intervention Name(s)
Low intra-abdominal pressure
Intervention Description
Lowering intra-abdominal pressure during laparoscopic surgery
Intervention Type
Drug
Intervention Name(s)
Rocuronium bromide
Other Intervention Name(s)
Deep muscle relaxation
Intervention Description
Deep (PTC 1-2) versus moderate (TOF count 1-2) neuromuscular block
Primary Outcome Measure Information:
Title
Mononuclear cell responsiveness ex vivo
Description
TNFalpha release upon LPS stimulation
Time Frame
Before surgery, 24 and 72 hours after surgery
Secondary Outcome Measure Information:
Title
Mononuclear cell responsiveness ex-vivo
Description
IL-6, IL-10 and IL-1beta release upon LPS stimulation
Time Frame
Before surgery, 24 and 72 hours after surgery
Title
Serum DAMPs and cytokines
Description
Danger associated molecular patterns, TNFalpha, IL-6 and IL-10
Time Frame
Before surgery, at the end of surgery and 24 hours after surgery
Title
HLA-DR mRNA expression
Description
MHC-II antigen presenting immune receptor
Time Frame
Before surgery, 24 and 72 hours after surgery
Title
Peritoneal histology and HIF1alpha expression
Description
Histology and HIF1alpha mRNA expression of a peritoneal biopsy
Time Frame
At the start and end of surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Scheduled for laparoscopic colorectal surgery with a primary anastomosis
Obtained informed consent
Age over 18 years
Exclusion Criteria:
Insufficient control of the Dutch language to read the patient information and to fill out the questionnaires
Primary colostomy
Neo-adjuvant chemotherapy
Chronic use of analgesics or psychotropic drugs
Use of NSAIDs shorter than 5 days before surgery
Known or suspected allergy to rocuronium of sugammadex
Neuromuscular disease
Indication for rapid sequence induction
Severe liver- or renal disease (creatinine clearance <30ml/min)
BMI >35 kg/m²
Deficiency of vitamin K dependent clotting factors or coagulopathy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kim I Albers, MD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michiel C Warlé, MD, PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Canisius Wilhelmina Hospital
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6532SZ
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
No
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The Effect of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery on Innate Immune Homeostasis.
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