Acute CholecystitisPUMASNCT04156711
Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery
A study testing Remote Ischemic Preconditioning (RIPC) in people with Acute Cholecystitis and Endothelial Dysfunction, run by Zealand University Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Acute Cholecystitis, Endothelial Dysfunction
- What is being tested?
- Remote Ischemic Preconditioning (RIPC)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteDenmark
- Study dates
- 4 Sep 2019to 14 Sep 2021
- Phase
- Interventional
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing acute or subacute cholecystectomy due to acute cholecystitis with a maximum of 7 days of symptoms prior to surgery
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Surgical Science, Surgical Department, Zealand University Hospital
Køge, Region Sjælland, 4600
About this study
Official title: Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery: The PUMAS Study
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.
Read the 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).
- Conditions
- Acute Cholecystitis, Endothelial Dysfunction
- Being tested
- Remote Ischemic Preconditioning (RIPC)
- Keywords
- Remote ISchemic Preconditioning (RIPC), Acute surgery, Acute cholecystitis, Endothelial dysfunction, Heart Rate Variability (HRV)
- Medical subject headings
- Cholecystitis, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote Ischemic Preconditioning (RIPC)Procedure or surgery
Cycles of forearm ischemia and reperfusion by the inflation of a blood-pressure cuff over the systemic blood pressure for brief periods
| Study group | Role | What they receive |
|---|---|---|
| Remote Ischemic Preconditioning | Experimental | 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 Receives: Procedure: Remote Ischemic Preconditioning (RIPC) |
| Control | No intervention | 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 24 hours
Secondary outcomes (28)
Heart rate variability
Changes in Heart rate variability measured with eMotion Faros from baseline and 24 hours consecutively.
Measured: 24 hours
Changes in p-L-arginine
Changes in p-L-arginine in μmol/L from baseline til 24h post-surgery
Measured: 24 hours
Changes in p-asymmetric dimethylarginine
Changes in p-asymmetric dimethylarginine in μmol/L from baseline til 24h post-surgery
Measured: 24 hours
Changes in p-biopterins
Changes in p-biopterins in ng/ml from baseline til 24h post-surgery
Measured: 24 hours
Changes in soluble endothelial (E-) selectin
Changes in soluble E-selectin in ng/ml from baseline til 24h post-surgery
Measured: 24 hours
Changes in soluble plasma (P-) selectin
Changes in soluble P-selectin in ng/ml from baseline til 24h post-surgery
Measured: 24 hours
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
Measured: 24 hours
Changes in syndecan-1
Changes in syndecan-1 in pg/ml from baseline til 24h post-surgery
Measured: 24 hours
Changes in thrombomodulin
Changes in thrombomodulin in pg/ml from baseline til 24h post-surgery
Measured: 24 hours
Changes in arginine vasopressin
Changes in arginine vasopressin in ng/ml from baseline til 24h post-surgery
Measured: 24 hours
Changes in adrenalin
Changes in adrenalin in ng/ml from baseline til 24h post-surgery
Measured: 24 hours
Changes in noradrenalin
Changes in noradrenalin in pg/ml from baseline til 24h post-surgery
Measured: 24 hours
Changes in ascorbic acid
Changes in ascorbic acid in ng/μL from baseline til 24h post-surgery
Measured: 24 hours
Changes in dehydroascorbic acid
Changes in dehydroascorbic acid in ng/μL from baseline til 24h post-surgery
Measured: 24 hours
Changes in angiotensin II
Changes in angiotensin II in pg/mL from baseline til 24h post-surgery
Measured: 24 hours
Changes in bradykinin
Changes in bradykinin in pg/mL from baseline til 24h post-surgery
Measured: 24 hours
Changes in calcitonin-gene related peptide
Changes in calcitonin-gene related peptide in pg/mL from baseline til 24h post-surgery
Measured: 24 hours
Changes in prostacyclin
Changes in prostacyclin in pg/mL from baseline til 24h post-surgery
Measured: 24 hours
Changes in serotonin
Changes in serotonin in ng/mL from baseline til 24h post-surgery
Measured: 24 hours
Changes in endothelin-1
Changes in endothelin-1 in pg/mL from baseline til 24h post-surgery
Measured: 24 hours
Changes in adrenomedullin
Changes in adrenomedullin in ng/mL from baseline til 24h post-surgery
Measured: 24 hours
Changes in platelets
Changes in platelets x 109/L from baseline til 24h post-surgery
Measured: 24 hours
Changes in adenosin
Changes in adenosin μmol/L from baseline til 24h post-surgery
Measured: 24 hours
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
Measured: 24 hours
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.
Measured: 4 hours
Local complications to RIPC
Pain, changed sensibility or decreased function of the upper extremity where remote ischemic preconditioning were carried out preoperatively.
Measured: 24 hours
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)
Measured: 30 days
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)
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2019
- Study start4 Sep 2019
- Primary completion14 Sep 2021
- Study completion14 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute CholecystitisStudies of the same condition, open and under way.
- More trials run by Zealand University HospitalThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kirsten L Wahlstroem, MD, Principal investigator, Center for Surgical Science, Zealand University Hospital,
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04156711
- Sponsor's protocol ID
- REG-020-2019
- Acronym
- PUMAS
- Status last verified
- Sep 2021
- First submitted
- 23 Sep 2019
- Last updated
- 29 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery: The PUMAS Study
- ClinicalTrials.gov ID
- NCT04156711
- Acronym / sponsor ID
- PUMAS / REG-020-2019
- Conditions
- Acute Cholecystitis, Endothelial Dysfunction
- Keywords
- Remote ISchemic Preconditioning (RIPC), Acute surgery, Acute cholecystitis, Endothelial dysfunction, Heart Rate Variability (HRV)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Study start
- 4 Sep 2019 (actual)
- Primary completion
- 14 Sep 2021 (actual)
- Study completion
- 14 Sep 2021 (actual)
- First posted
- 7 Nov 2019 (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.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Remote Ischemic Preconditioning | Experimental | Procedure: Remote Ischemic Preconditioning (RIPC)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 |
| Control | No intervention | –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) |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients undergoing acute or subacute cholecystectomy due to acute cholecystitis with a maximum of 7 days of symptoms prior to surgery
Key exclusion criteria (6 listed)
- 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
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 |
|---|---|---|
| Remote Ischemic Preconditioning (RIPC)Cycles of forearm ischemia and reperfusion by the inflation of a blood-pressure cuff over the systemic blood pressure for brief periods | Procedure or surgery | Remote Ischemic Preconditioning |
Primary outcome
Changes in endothelial function measured by reactive hyperemia index (RHI)
Time frame: 24 hours
Changes in endothelial function measured by reactive hyperemia index (RHI) at baseline, four hours and 24 hours after surgery (cholecystectomy due to acute cholecystitis)
28 secondary outcomes
Heart rate variability
Time frame: 24 hours
Changes in p-L-arginine
Time frame: 24 hours
Changes in p-asymmetric dimethylarginine
Time frame: 24 hours
Changes in p-biopterins
Time frame: 24 hours
Changes in soluble endothelial (E-) selectin
Time frame: 24 hours
Changes in soluble plasma (P-) selectin
Time frame: 24 hours
Changes in Intercellular Adhesion Molecule 1 (ICAM-1)
Time frame: 24 hours
Changes in syndecan-1
Time frame: 24 hours
Changes in thrombomodulin
Time frame: 24 hours
Changes in arginine vasopressin
Time frame: 24 hours
Changes in adrenalin
Time frame: 24 hours
Changes in noradrenalin
Time frame: 24 hours
Changes in ascorbic acid
Time frame: 24 hours
Changes in dehydroascorbic acid
Time frame: 24 hours
Changes in angiotensin II
Time frame: 24 hours
Changes in bradykinin
Time frame: 24 hours
Changes in calcitonin-gene related peptide
Time frame: 24 hours
Changes in prostacyclin
Time frame: 24 hours
Changes in serotonin
Time frame: 24 hours
Changes in endothelin-1
Time frame: 24 hours
Changes in adrenomedullin
Time frame: 24 hours
Changes in platelets
Time frame: 24 hours
Changes in adenosin
Time frame: 24 hours
Changes in interleukin-6(IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta)
Time frame: 24 hours
Changes in gene expression autoimmune human pathway panel from NanoString
Time frame: 4 hours
Local complications to RIPC
Time frame: 24 hours
Differences in postoperative quality of recovery score 15 (QoR-15) between arms in the trial
Time frame: 30 days
Differences in Self reported pain on a 0-10 scale between arms in the trial
Time frame: 24 hours
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 29 Sep 2021.
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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.
Kirsten L Wahlstroem, MD principal investigator
Center for Surgical Science, Zealand University Hospital,
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Remote Ischemic Preconditioning (RIPC) in people with Acute Cholecystitis and Endothelial Dysfunction, run by Zealand University Hospital at 1 site in Denmark.
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 1 inclusion and 6 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 29 Sep 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 Denmark. 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.
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?
Changes in endothelial function measured by reactive hyperemia index (RHI) (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Sep 2021.