Hemorrhagic ShockNCT02071290
Effect of Remote Ischemic Conditioning on Trauma Patients With Hemorrhagic Shock
A study testing Pneumatic tourniquet in people with Hemorrhagic Shock, run by Unity Health Toronto at 1 site in Canada.
Trial summary
The purpose of the study is to evaluate whether remote ischemic conditioning is a safe and effective intervention to prevent the development of inflammation and coagulopathy in trauma patients with hemorrhagic shock. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Hemorrhagic Shock
- What is being tested?
- Pneumatic tourniquet
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- May 2015to Jan 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥16 years of age or estimated weight ≥50kgs if age is unknown;
- Victim of blunt or penetrating trauma
- Hemorrhagic shock defined as:
- One or more episodes of systolic blood pressure ≤90mmHg at any time prior to enrollment into the study;
- An identified source of blood loss (abdomen, chest, pelvis/retroperitoneum, extremities, external) or
- Blood products (RBC, Platelets, Plasma, etc.) has been ordered to the trauma room.
- Admitted to St. Michael's Hospital directly from the scene of injury within 3 hours of the injury
- Application and completion of Remote Ischemic Conditioning (RIC) within 4 hours of the injury
Who cannot join
- Pregnancy
- Non-hemorrhagic shock (i.e. tension pneumothorax, cardiac tamponade, spinal shock, etc.)
- Major burns > 20% total body surface area
- Fracture of both lower extremities (i.e. traumatic amputation, fractures)
- Absence of vital signs prior to admission, ongoing CPR, possibly dead on admission or not expected to survive beyond a few hours.
- Injury in both legs (traumatic amputation, fractures, etc.)
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- Patients with a systolic blood pressure above 200mmHg
- Patients treated with anticoagulants, antiplatelet therapy (Warfarin, Aspirin), steroids or with a known bleeding disorder or known abnormality of blood flow to the limb (if known)
- Patients with osteoporosis or other bone disorders, peripheral nerve injury, abnormal nerve supply, peripheral neuropathy (if known) or preexisting traumatic injury to the limb.
- Morbid obesity (largest cuff size won't fit)
- If RIC is done clinically before research protocol begins.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Remote Ischemic Conditioning on Neutrophil Function and the Immune-Inflammatory and Coagulation Profiles in Trauma Patients With Hemorrhagic Shock
The purpose of the study is to evaluate whether remote ischemic conditioning is a safe and effective intervention to prevent the development of inflammation and coagulopathy in trauma patients with hemorrhagic shock.
Read the detailed description
Dysfunction of vital organs is one of the major reasons why trauma victims die after sustaining a major injury, even though the organs themselves may not have been directly injured. The inability to clot blood as a result of inflammation further contributes to complications in a majority of these patients. One intervention proposed to protect against impaired organ function is called "Remote Ischemic Conditioning", wherein application of intermittent occlusion and release of blood flow to the arm by sequentially inflating and deflating a blood pressure cuff can protect against the development of distant organ injury and inflammation following a severe traumatic event. In a pilot study, we will investigate the effects of remote ischemic conditioning in trauma patients with hemorrhagic shock, with a view to evaluate its effects on the immune system and coagulation profiles, both of which are known to be deranged in these patients. These studies will potentially benefit patients and will serve as a proof of principle for the use of remote ischemic conditioning in the trauma setting.
- Conditions
- Hemorrhagic Shock
- Being tested
- Pneumatic tourniquet
- Keywords
- Hemorrhagic Shock, Remote Ischemic Conditioning
- Medical subject headings
- Shock, Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pneumatic tourniquetDevice
Four cycles of brief occlusion of bloodflow to the thigh (5 minutes) followed by reperfusion (5 minutes) using a pneumatic tourniquet
Remote Ischemic Conditioning
| Study group | Role | What they receive |
|---|---|---|
| Sham Remote Ischemic Conditioning | Sham comparator | Sham inflation of pneumatic tourniquet pressure cuff at 0 mmHg on the thigh for 5 minutes and release for 5 minutes (repeated for 4 cycles) applied to trauma patients on arrival to hospital Receives: Device: Pneumatic tourniquet |
| Remote Ischemic Conditioning | Experimental | Inflation of pneumatic tourniquet pressure cuff at 250mmHg on the thigh for 5 minutes and release for 5 minutes (repeated for 4 cycles) applied to trauma patients on arrival to hospital Receives: Device: Pneumatic tourniquet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neutrophil Oxidative Burst Activity
Change in neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Measured: 0 (Admission), 1, 3, and 24 hours after intervention
Neutrophil Oxidative Burst Activity (PMA Stimulated)
Change in PMA stimulated neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours. Measured by flow cytometry using whole blood samples.
Measured: 0 (Admission), 1, 3, and 24 hours after intervention
Neutrophil Adhesion Molecule Expression (CD11b)
Change in neutrophil adhesion molecule (CD11b) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Measured: 0 (Admission), 1, 3, 24 hours after intervention
Neutrophil Adhesion Molecule Expression (CD62L)
Change in neutrophil adhesion molecule (CD62L) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Measured: 0 (Admission), 1, 3, and 24 hours after intervention
Endothelial Injury (Heparan Sulfate)
Change in plasma levels of endothelial injury marker Heparan Sulfate over 24 hours from Admission
Measured: 0 (Admission), 1, 3, and 24 hours after intervention
Endothelial Injury (Hyaluronan)
Change in plasma levels of endothelial injury marker Hyaluronan over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
Endothelial Injury (Syndecan-1)
Change in plasma levels of endothelial injury marker Syndecan-1 over 24 hours from Admission
Measured: 0 (Admission), 1, 3, and 24 hours after intervention
Plasma TNF-α
Change in plasma levels of inflammatory mediator TNF-α over 24 hours from Admission
Measured: 0 (Admission), 1, 3, and 24 hours after intervention
Plasma IL-6
Change in plasma levels of inflammatory mediator IL-6 over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
Plasma IL-8
Change in plasma levels of inflammatory mediator IL-8 over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
Plasma IL-10
Change in plasma levels of anti-inflammatory mediator IL-10 over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
ROTEM EXTEM CT
Change in ROTEM parameter Clotting Time (CT) over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
ROTEM EXTEM CFT
Change in ROTEM parameter Clot Formation Time (CFT) over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
ROTEM EXTEM A10
Change in ROTEM parameter A10 over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
ROTEM EXTEM Alpha Angle
Change in ROTEM parameter Alpha Angle over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
ROTEM EXTEM ML
Change in ROTEM parameter maximum lysis (ML) over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
Plasma D-Dimer
Change in plasma D-Dimer levels over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
Plasma Protein C
Change in plasma Protein C levels over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
Plasma Fibrinogen
Change in plasma fibrinogen levels over 24 hours from Admission
Measured: 0 (Admission), 1, 3, 24 hours
Secondary outcomes (6)
Ventilator Free Days
Secondary clinical outcomes
Measured: up to 28 days or discharge
ICU Free Days
Secondary clinical outcomes
Measured: up to 28 days or discharge
Hospital Free Days
Secondary clinical outcomes
Measured: up to 28 days or discharge
Nosocomial Infections
Secondary clinical outcomes
Measured: up to 28 days or discharge
24 Hour Mortality
Secondary clinical outcomes
Measured: up to 28 days or discharge
28 Day Mortality
Secondary clinical outcomes
Measured: up to 28 days or discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2014 (estimated)
- Study startMay 2015
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemorrhagic ShockStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ori D Rotstein, MD, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02071290
- Sponsor's protocol ID
- SMH-RIC-01
- Status last verified
- May 2023
- First submitted
- 18 Feb 2014
- Last updated
- 7 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Leung CH, Rizoli SB, Trypcic S, Rhind SG, Battista AP, Ailenberg M, Rotstein OD. Effect of remote ischemic conditioning on the immune-inflammatory profile in patients with traumatic hemorrhagic shock in a randomized controlled trial. Sci Rep. 2023 Apr 29;13(1):7025. doi: 10.1038/s41598-023-33681-3.
PubMed 37120600
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Remote Ischemic Conditioning on Neutrophil Function and the Immune-Inflammatory and Coagulation Profiles in Trauma Patients With Hemorrhagic Shock
- ClinicalTrials.gov ID
- NCT02071290
- Acronym / sponsor ID
- SMH-RIC-01
- Conditions
- Hemorrhagic Shock
- Keywords
- Hemorrhagic Shock, Remote Ischemic Conditioning
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- May 2015 (actual)
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 25 Feb 2014 (estimated)
- Results
- Posted 27 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to evaluate whether remote ischemic conditioning is a safe and effective intervention to prevent the development of inflammation and coagulopathy in trauma patients with hemorrhagic shock.
Detailed description
Dysfunction of vital organs is one of the major reasons why trauma victims die after sustaining a major injury, even though the organs themselves may not have been directly injured. The inability to clot blood as a result of inflammation further contributes to complications in a majority of these patients. One intervention proposed to protect against impaired organ function is called "Remote Ischemic Conditioning", wherein application of intermittent occlusion and release of blood flow to the arm by sequentially inflating and deflating a blood pressure cuff can protect against the development of distant organ injury and inflammation following a severe traumatic event. In a pilot study, we will investigate the effects of remote ischemic conditioning in trauma patients with hemorrhagic shock, with a view to evaluate its effects on the immune system and coagulation profiles, both of which are known to be deranged in these patients. These studies will potentially benefit patients and will serve as a proof of principle for the use of remote ischemic conditioning in the trauma setting.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sham Remote Ischemic Conditioning | Sham comparator | Device: Pneumatic tourniquetSham inflation of pneumatic tourniquet pressure cuff at 0 mmHg on the thigh for 5 minutes and release for 5 minutes (repeated for 4 cycles) applied to trauma patients on arrival to hospital |
| Remote Ischemic Conditioning | Experimental | Device: Pneumatic tourniquetInflation of pneumatic tourniquet pressure cuff at 250mmHg on the thigh for 5 minutes and release for 5 minutes (repeated for 4 cycles) applied to trauma patients on arrival to hospital |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥16 years of age or estimated weight ≥50kgs if age is unknown;
- Victim of blunt or penetrating trauma
- Hemorrhagic shock defined as:
- One or more episodes of systolic blood pressure ≤90mmHg at any time prior to enrollment into the study;
- An identified source of blood loss (abdomen, chest, pelvis/retroperitoneum, extremities, external) or
Key exclusion criteria (11 listed)
- Pregnancy
- Non-hemorrhagic shock (i.e. tension pneumothorax, cardiac tamponade, spinal shock, etc.)
- Major burns > 20% total body surface area
- Fracture of both lower extremities (i.e. traumatic amputation, fractures)
- Absence of vital signs prior to admission, ongoing CPR, possibly dead on admission or not expected to survive beyond a few hours.
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 |
|---|---|---|
| Pneumatic tourniquetFour cycles of brief occlusion of bloodflow to the thigh (5 minutes) followed by reperfusion (5 minutes) using a pneumatic tourniquet Remote Ischemic Conditioning | Device | Remote Ischemic Conditioning, Sham Remote Ischemic Conditioning |
Primary outcome
Neutrophil Oxidative Burst Activity
Time frame: 0 (Admission), 1, 3, and 24 hours after intervention
Change in neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Neutrophil Oxidative Burst Activity (PMA Stimulated)
Time frame: 0 (Admission), 1, 3, and 24 hours after intervention
Change in PMA stimulated neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours. Measured by flow cytometry using whole blood samples.
Neutrophil Adhesion Molecule Expression (CD11b)
Time frame: 0 (Admission), 1, 3, 24 hours after intervention
Change in neutrophil adhesion molecule (CD11b) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Neutrophil Adhesion Molecule Expression (CD62L)
Time frame: 0 (Admission), 1, 3, and 24 hours after intervention
Change in neutrophil adhesion molecule (CD62L) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.
Endothelial Injury (Heparan Sulfate)
Time frame: 0 (Admission), 1, 3, and 24 hours after intervention
Change in plasma levels of endothelial injury marker Heparan Sulfate over 24 hours from Admission
Endothelial Injury (Hyaluronan)
Time frame: 0 (Admission), 1, 3, 24 hours
Change in plasma levels of endothelial injury marker Hyaluronan over 24 hours from Admission
Endothelial Injury (Syndecan-1)
Time frame: 0 (Admission), 1, 3, and 24 hours after intervention
Change in plasma levels of endothelial injury marker Syndecan-1 over 24 hours from Admission
Plasma TNF-α
Time frame: 0 (Admission), 1, 3, and 24 hours after intervention
Change in plasma levels of inflammatory mediator TNF-α over 24 hours from Admission
Plasma IL-6
Time frame: 0 (Admission), 1, 3, 24 hours
Change in plasma levels of inflammatory mediator IL-6 over 24 hours from Admission
Plasma IL-8
Time frame: 0 (Admission), 1, 3, 24 hours
Change in plasma levels of inflammatory mediator IL-8 over 24 hours from Admission
Plasma IL-10
Time frame: 0 (Admission), 1, 3, 24 hours
Change in plasma levels of anti-inflammatory mediator IL-10 over 24 hours from Admission
ROTEM EXTEM CT
Time frame: 0 (Admission), 1, 3, 24 hours
Change in ROTEM parameter Clotting Time (CT) over 24 hours from Admission
ROTEM EXTEM CFT
Time frame: 0 (Admission), 1, 3, 24 hours
Change in ROTEM parameter Clot Formation Time (CFT) over 24 hours from Admission
ROTEM EXTEM A10
Time frame: 0 (Admission), 1, 3, 24 hours
Change in ROTEM parameter A10 over 24 hours from Admission
ROTEM EXTEM Alpha Angle
Time frame: 0 (Admission), 1, 3, 24 hours
Change in ROTEM parameter Alpha Angle over 24 hours from Admission
ROTEM EXTEM ML
Time frame: 0 (Admission), 1, 3, 24 hours
Change in ROTEM parameter maximum lysis (ML) over 24 hours from Admission
Plasma D-Dimer
Time frame: 0 (Admission), 1, 3, 24 hours
Change in plasma D-Dimer levels over 24 hours from Admission
Plasma Protein C
Time frame: 0 (Admission), 1, 3, 24 hours
Change in plasma Protein C levels over 24 hours from Admission
Plasma Fibrinogen
Time frame: 0 (Admission), 1, 3, 24 hours
Change in plasma fibrinogen levels over 24 hours from Admission
6 secondary outcomes
Ventilator Free Days
Time frame: up to 28 days or discharge
ICU Free Days
Time frame: up to 28 days or discharge
Hospital Free Days
Time frame: up to 28 days or discharge
Nosocomial Infections
Time frame: up to 28 days or discharge
24 Hour Mortality
Time frame: up to 28 days or discharge
28 Day Mortality
Time frame: up to 28 days or discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37120600Leung CH, Rizoli SB, Trypcic S, Rhind SG, Battista AP, Ailenberg M, Rotstein OD. Effect of remote ischemic conditioning on the immune-inflammatory profile in patients with traumatic hemorrhagic shock in a randomized controlled trial. Sci Rep. 2023 Apr 29;13(1):7025. doi: 10.1038/s41598-023-33681-3.
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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.
Ori D Rotstein, MD principal investigator
Unity Health Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pneumatic tourniquet in people with Hemorrhagic Shock, run by Unity Health Toronto at 1 site in Canada.
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 8 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 7 Jun 2023. 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 Canada. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 27 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Neutrophil Oxidative Burst Activity (time frame: 0 (Admission), 1, 3, and 24 hours after intervention). The study lists 19 primary outcomes in all. 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 NCT02071290, 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 7 Jun 2023.