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Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery (PUMAS)

Primary Purpose

Acute Cholecystitis, Endothelial Dysfunction

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Remote Ischemic Preconditioning (RIPC)
Sponsored by
Zealand University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Cholecystitis focused on measuring Remote ISchemic Preconditioning (RIPC), Acute surgery, Acute cholecystitis, Endothelial dysfunction, Heart Rate Variability (HRV)

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients undergoing acute or subacute cholecystectomy due to acute cholecystitis with a maximum of 7 days of symptoms prior to surgery

Exclusion Criteria:

  • Not capable of giving informed consent after oral and written information
  • Surgery within 30 days of study inclusion
  • Conditions that prevent the performance of remote ischemic preconditioning on the upper extremity, e.g. fractures, paresis, lymphedema
  • performance of concomitant endoscopic retrograde cholangiopancreatography (ERCP) during surgery
  • synchronous pancreatitis
  • synchronous cholangitis

Sites / Locations

  • Center for Surgical Science, Surgical Department, Zealand University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Remote Ischemic Preconditioning

Control

Arm Description

Remote ischemic preconditioning is carried out before the induction of general anesthesia. All four cycles will be completed before general anesthesia. The blood pressure cuff is placed on the upper limb. The cuff is inflated to 200 mmHg (if systolic blood pressures exceeds 185 mmHg, the cuff will be inflated to at least 15 mmHg above the systolic blood pressure) resulting in a total occlusion of the blood flow to the limb. After 5 minutes of ischemia, the cuff is deflated, and the limb is reperfused for 5 minutes. This cycle is repeated 4 times. Pulse oximetry is performed on the RIPC limb to make sure that the blood flow is completely interrupted during ischemia

Will receive no intervention, but will go through same tests at the same time-points (endothelial function measured by reactive hyperemia index, blood samples, Heart rate variability and questionaires)

Outcomes

Primary Outcome Measures

Changes in endothelial function measured by reactive hyperemia index (RHI)
Changes in endothelial function measured by reactive hyperemia index (RHI) at baseline, four hours and 24 hours after surgery (cholecystectomy due to acute cholecystitis)

Secondary Outcome Measures

Heart rate variability
Changes in Heart rate variability measured with eMotion Faros from baseline and 24 hours consecutively.
Changes in p-L-arginine
Changes in p-L-arginine in μmol/L from baseline til 24h post-surgery
Changes in p-asymmetric dimethylarginine
Changes in p-asymmetric dimethylarginine in μmol/L from baseline til 24h post-surgery
Changes in p-biopterins
Changes in p-biopterins in ng/ml from baseline til 24h post-surgery
Changes in soluble endothelial (E-) selectin
Changes in soluble E-selectin in ng/ml from baseline til 24h post-surgery
Changes in soluble plasma (P-) selectin
Changes in soluble P-selectin in ng/ml from baseline til 24h post-surgery
Changes in Intercellular Adhesion Molecule 1 (ICAM-1)
Changes in soluble Intercellular Adhesion Molecule 1 (ICAM-1) in ng/ml from baseline til 24h post-surgery
Changes in syndecan-1
Changes in syndecan-1 in pg/ml from baseline til 24h post-surgery
Changes in thrombomodulin
Changes in thrombomodulin in pg/ml from baseline til 24h post-surgery
Changes in arginine vasopressin
Changes in arginine vasopressin in ng/ml from baseline til 24h post-surgery
Changes in adrenalin
Changes in adrenalin in ng/ml from baseline til 24h post-surgery
Changes in noradrenalin
Changes in noradrenalin in pg/ml from baseline til 24h post-surgery
Changes in ascorbic acid
Changes in ascorbic acid in ng/μL from baseline til 24h post-surgery
Changes in dehydroascorbic acid
Changes in dehydroascorbic acid in ng/μL from baseline til 24h post-surgery
Changes in angiotensin II
Changes in angiotensin II in pg/mL from baseline til 24h post-surgery
Changes in bradykinin
Changes in bradykinin in pg/mL from baseline til 24h post-surgery
Changes in calcitonin-gene related peptide
Changes in calcitonin-gene related peptide in pg/mL from baseline til 24h post-surgery
Changes in prostacyclin
Changes in prostacyclin in pg/mL from baseline til 24h post-surgery
Changes in serotonin
Changes in serotonin in ng/mL from baseline til 24h post-surgery
Changes in endothelin-1
Changes in endothelin-1 in pg/mL from baseline til 24h post-surgery
Changes in adrenomedullin
Changes in adrenomedullin in ng/mL from baseline til 24h post-surgery
Changes in platelets
Changes in platelets x 109/L from baseline til 24h post-surgery
Changes in adenosin
Changes in adenosin μmol/L from baseline til 24h post-surgery
Changes in interleukin-6(IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta)
Changes in IL-6, IL-10, TNF-Alpha, TGF-beta in pg/mL from baseline til 24h post-surgery
Changes in gene expression autoimmune human pathway panel from NanoString
Changes in gene expression profiles in the autoimmune human pathway panel from NanoString from baseline until four hours post-surgery.
Local complications to RIPC
Pain, changed sensibility or decreased function of the upper extremity where remote ischemic preconditioning were carried out preoperatively.
Differences in postoperative quality of recovery score 15 (QoR-15) between arms in the trial
Questionnaire on Postoperative quality of recovery with 15 questions comparing scores from baseline, 24 hours and 30 days after surgery between study arms (intervention and controls)
Differences in Self reported pain on a 0-10 scale between arms in the trial
Self reported pain on a 0-10 scale at baseline and 24 hours after surgery between study arms (intervention and controls)

Full Information

First Posted
September 23, 2019
Last Updated
September 23, 2021
Sponsor
Zealand University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04156711
Brief Title
Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery
Acronym
PUMAS
Official Title
Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery: The PUMAS Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
September 4, 2019 (Actual)
Primary Completion Date
September 14, 2021 (Actual)
Study Completion Date
September 14, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zealand University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study examines if remote ischemic preconditioning in patients undergoing minor acute abdominal surgery (laparoscopic cholecystitis due to acute cholecystitis) is associated with a modulation of endothelial dysfunction. half of the patients will receive remote ischemic preconditioning prior to surgery, the other half will serve as controls.
Detailed Description
Remote ischemic preconditioning (RIPC) consists of cycles of forearm or leg ischemia and reperfusion by the inflation of a blood-pressure cuff over the systemic blood pressure for brief periods. The procedure is simple, safe and with no clear side effects. In clinical studies covering acute cardiology RIPC has effectively reduced myocardial injury, postoperative cardiovascular complications and cardiac mortality. Recently, the effect of RIPC on attenuating ischemia-reperfusion injury has been investigated in non-cardiac surgery as well. The organ specific ischemia-reperfusion injury, systemic oxidative stress and inflammatory response were attenuated due to the intervention but a complete understanding of the underlying protective mechanisms of RIPC is however still lacking. Experimental and clinical studies have implicated that the stimulus of RIPC is transmitted from the preconditioned tissue to other tissues and organs by humoral, neural and systemic anti-inflammatory mediators. The humoral and neural pathway are thought to be dependent on endogen substances such as adenosine, bradykinin, nitrogen oxide (NO) and calcitonin-gene-related-peptide (CGRP).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Cholecystitis, Endothelial Dysfunction
Keywords
Remote ISchemic Preconditioning (RIPC), Acute surgery, Acute cholecystitis, Endothelial dysfunction, Heart Rate Variability (HRV)

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Care ProviderOutcomes Assessor
Masking Description
Outcomes assessor are partly blinded and data analysis will be blinded
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Remote Ischemic Preconditioning
Arm Type
Experimental
Arm Description
Remote ischemic preconditioning is carried out before the induction of general anesthesia. All four cycles will be completed before general anesthesia. The blood pressure cuff is placed on the upper limb. The cuff is inflated to 200 mmHg (if systolic blood pressures exceeds 185 mmHg, the cuff will be inflated to at least 15 mmHg above the systolic blood pressure) resulting in a total occlusion of the blood flow to the limb. After 5 minutes of ischemia, the cuff is deflated, and the limb is reperfused for 5 minutes. This cycle is repeated 4 times. Pulse oximetry is performed on the RIPC limb to make sure that the blood flow is completely interrupted during ischemia
Arm Title
Control
Arm Type
No Intervention
Arm Description
Will receive no intervention, but will go through same tests at the same time-points (endothelial function measured by reactive hyperemia index, blood samples, Heart rate variability and questionaires)
Intervention Type
Procedure
Intervention Name(s)
Remote Ischemic Preconditioning (RIPC)
Intervention Description
Cycles of forearm ischemia and reperfusion by the inflation of a blood-pressure cuff over the systemic blood pressure for brief periods
Primary Outcome Measure Information:
Title
Changes in endothelial function measured by reactive hyperemia index (RHI)
Description
Changes in endothelial function measured by reactive hyperemia index (RHI) at baseline, four hours and 24 hours after surgery (cholecystectomy due to acute cholecystitis)
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Heart rate variability
Description
Changes in Heart rate variability measured with eMotion Faros from baseline and 24 hours consecutively.
Time Frame
24 hours
Title
Changes in p-L-arginine
Description
Changes in p-L-arginine in μmol/L from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in p-asymmetric dimethylarginine
Description
Changes in p-asymmetric dimethylarginine in μmol/L from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in p-biopterins
Description
Changes in p-biopterins in ng/ml from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in soluble endothelial (E-) selectin
Description
Changes in soluble E-selectin in ng/ml from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in soluble plasma (P-) selectin
Description
Changes in soluble P-selectin in ng/ml from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in Intercellular Adhesion Molecule 1 (ICAM-1)
Description
Changes in soluble Intercellular Adhesion Molecule 1 (ICAM-1) in ng/ml from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in syndecan-1
Description
Changes in syndecan-1 in pg/ml from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in thrombomodulin
Description
Changes in thrombomodulin in pg/ml from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in arginine vasopressin
Description
Changes in arginine vasopressin in ng/ml from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in adrenalin
Description
Changes in adrenalin in ng/ml from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in noradrenalin
Description
Changes in noradrenalin in pg/ml from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in ascorbic acid
Description
Changes in ascorbic acid in ng/μL from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in dehydroascorbic acid
Description
Changes in dehydroascorbic acid in ng/μL from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in angiotensin II
Description
Changes in angiotensin II in pg/mL from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in bradykinin
Description
Changes in bradykinin in pg/mL from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in calcitonin-gene related peptide
Description
Changes in calcitonin-gene related peptide in pg/mL from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in prostacyclin
Description
Changes in prostacyclin in pg/mL from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in serotonin
Description
Changes in serotonin in ng/mL from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in endothelin-1
Description
Changes in endothelin-1 in pg/mL from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in adrenomedullin
Description
Changes in adrenomedullin in ng/mL from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in platelets
Description
Changes in platelets x 109/L from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in adenosin
Description
Changes in adenosin μmol/L from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in interleukin-6(IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta)
Description
Changes in IL-6, IL-10, TNF-Alpha, TGF-beta in pg/mL from baseline til 24h post-surgery
Time Frame
24 hours
Title
Changes in gene expression autoimmune human pathway panel from NanoString
Description
Changes in gene expression profiles in the autoimmune human pathway panel from NanoString from baseline until four hours post-surgery.
Time Frame
4 hours
Title
Local complications to RIPC
Description
Pain, changed sensibility or decreased function of the upper extremity where remote ischemic preconditioning were carried out preoperatively.
Time Frame
24 hours
Title
Differences in postoperative quality of recovery score 15 (QoR-15) between arms in the trial
Description
Questionnaire on Postoperative quality of recovery with 15 questions comparing scores from baseline, 24 hours and 30 days after surgery between study arms (intervention and controls)
Time Frame
30 days
Title
Differences in Self reported pain on a 0-10 scale between arms in the trial
Description
Self reported pain on a 0-10 scale at baseline and 24 hours after surgery between study arms (intervention and controls)
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients undergoing acute or subacute cholecystectomy due to acute cholecystitis with a maximum of 7 days of symptoms prior to surgery Exclusion Criteria: Not capable of giving informed consent after oral and written information Surgery within 30 days of study inclusion Conditions that prevent the performance of remote ischemic preconditioning on the upper extremity, e.g. fractures, paresis, lymphedema performance of concomitant endoscopic retrograde cholangiopancreatography (ERCP) during surgery synchronous pancreatitis synchronous cholangitis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kirsten L Wahlstroem, MD
Organizational Affiliation
Center for Surgical Science, Zealand University Hospital,
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Surgical Science, Surgical Department, Zealand University Hospital
City
Køge
State/Province
Zealand
ZIP/Postal Code
4600
Country
Denmark

12. IPD Sharing Statement

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Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery

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