PneumoperitoneumPhase 4RECOVER-PLUSNCT03572413
The Effect of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery on Innate Immune Homeostasis.
A Phase 4 study testing Low pressure pneumoperitoneum and Rocuronium bromide in people with Pneumoperitoneum and Neuromuscular Blockade, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pneumoperitoneum, Neuromuscular Blockade, Surgery
- What is being tested?
- Low pressure pneumoperitoneum and Rocuronium bromide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteNetherlands
- Study dates
- 24 Oct 2018to 1 Dec 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Scheduled for laparoscopic colorectal surgery with a primary anastomosis
- Obtained informed consent
- Age over 18 years
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Canisius Wilhelmina Hospital
Nijmegen, Gelderland, 6532SZ
About this study
Official title: The Effectiveness of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery in Preserving Innate Immune Homeostasis by Reducing Peritoneal Mesothelial Cell Injury.
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.
Read the 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.
- Conditions
- Pneumoperitoneum, Neuromuscular Blockade, Surgery, Immune Suppression
- Being tested
- Low pressure pneumoperitoneum, Rocuronium bromide
- Keywords
- Laparoscopic surgery, Deep neuromuscular block, Low pressure pneumoperitoneum, Postoperative immune suppression
- Medical subject headings
- Pneumoperitoneum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low pressure pneumoperitoneumProcedure or surgery
Also called Low intra-abdominal pressure
Lowering intra-abdominal pressure during laparoscopic surgery
Rocuronium bromideDrug
Also called Deep muscle relaxation
Deep (PTC 1-2) versus moderate (TOF count 1-2) neuromuscular block
| Study group | Role | What they receive |
|---|---|---|
| Low pressure PNP, deep NMB | Experimental | 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. Receives: Procedure: Low pressure pneumoperitoneum; Drug: Rocuronium bromide |
| Normal pressure PNP, moderate NMB | Active comparator | 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. Receives: Drug: Rocuronium bromide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mononuclear cell responsiveness ex vivo
TNFalpha release upon LPS stimulation
Measured: Before surgery, 24 and 72 hours after surgery
Secondary outcomes (4)
Mononuclear cell responsiveness ex-vivo
IL-6, IL-10 and IL-1beta release upon LPS stimulation
Measured: Before surgery, 24 and 72 hours after surgery
Serum DAMPs and cytokines
Danger associated molecular patterns, TNFalpha, IL-6 and IL-10
Measured: Before surgery, at the end of surgery and 24 hours after surgery
HLA-DR mRNA expression
MHC-II antigen presenting immune receptor
Measured: Before surgery, 24 and 72 hours after surgery
Peritoneal histology and HIF1alpha expression
Histology and HIF1alpha mRNA expression of a peritoneal biopsy
Measured: At the start and end of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2018
- Study start24 Oct 2018
- Primary completion31 Aug 2020
- Study completion1 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PneumoperitoneumStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Kim I Albers, MD, Principal investigator, Radboud University Medical CenterMichiel C Warlé, MD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03572413
- Sponsor's protocol ID
- NL65290.091.18 substudy
- Acronym
- RECOVER-PLUS
- Status last verified
- Mar 2021
- First submitted
- 18 Jun 2018
- Last updated
- 3 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Albers-Warle KI, Helder LS, Groh LA, Polat F, Panhuizen IF, Snoeck MMJ, Kox M, van Eijk L, Joosten LAB, Netea MG, Negishi Y, Mhlanga M, Keijzer C, Scheffer GJ, Warle MC. Postoperative Innate Immune Dysregulation, Proteomic, and Monocyte Epigenomic Changes After Colorectal Surgery: A Substudy of a Randomized Controlled Trial. Anesth Analg. 2025 Jan 1;140(1):185-196. doi: 10.1213/ANE.0000000000007297. Epub 2024 Oct 25.
PubMed 39453841
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of Low Pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery in Preserving Innate Immune Homeostasis by Reducing Peritoneal Mesothelial Cell Injury.
- ClinicalTrials.gov ID
- NCT03572413
- Acronym / sponsor ID
- RECOVER-PLUS / NL65290.091.18 substudy
- Conditions
- Pneumoperitoneum, Neuromuscular Blockade, Surgery, Immune Suppression
- Keywords
- Laparoscopic surgery, Deep neuromuscular block, Low pressure pneumoperitoneum, Postoperative immune suppression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 24 Oct 2018 (actual)
- Primary completion
- 31 Aug 2020 (actual)
- Study completion
- 1 Dec 2020 (actual)
- First posted
- 28 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low pressure PNP, deep NMB | Experimental | Procedure: Low pressure pneumoperitoneum, Drug: Rocuronium bromideLow 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 PNP, moderate NMB | Active comparator | Drug: Rocuronium bromideNormal 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Scheduled for laparoscopic colorectal surgery with a primary anastomosis
- Obtained informed consent
- Age over 18 years
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low pressure pneumoperitoneumAlso: Low intra-abdominal pressureLowering intra-abdominal pressure during laparoscopic surgery | Procedure or surgery | Low pressure PNP, deep NMB |
| Rocuronium bromideAlso: Deep muscle relaxationDeep (PTC 1-2) versus moderate (TOF count 1-2) neuromuscular block | Drug | Low pressure PNP, deep NMB, Normal pressure PNP, moderate NMB |
Primary outcome
Mononuclear cell responsiveness ex vivo
Time frame: Before surgery, 24 and 72 hours after surgery
TNFalpha release upon LPS stimulation
4 secondary outcomes
Mononuclear cell responsiveness ex-vivo
Time frame: Before surgery, 24 and 72 hours after surgery
Serum DAMPs and cytokines
Time frame: Before surgery, at the end of surgery and 24 hours after surgery
HLA-DR mRNA expression
Time frame: Before surgery, 24 and 72 hours after surgery
Peritoneal histology and HIF1alpha expression
Time frame: At the start and end of surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2021.
- Derived from this study: PubMed 39453841Albers-Warle KI, Helder LS, Groh LA, Polat F, Panhuizen IF, Snoeck MMJ, Kox M, van Eijk L, Joosten LAB, Netea MG, Negishi Y, Mhlanga M, Keijzer C, Scheffer GJ, Warle MC. Postoperative Innate Immune Dysregulation, Proteomic, and Monocyte Epigenomic Changes After Colorectal Surgery: A Substudy of a Randomized Controlled Trial. Anesth Analg. 2025 Jan 1;140(1):185-196. doi: 10.1213/ANE.0000000000007297. Epub 2024 Oct 25.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kim I Albers, MD principal investigator
Radboud University Medical Center
Michiel C Warlé, MD, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Low pressure pneumoperitoneum and Rocuronium bromide in people with Pneumoperitoneum and Neuromuscular Blockade, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mononuclear cell responsiveness ex vivo (time frame: Before surgery, 24 and 72 hours after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03572413, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2021.