Myocardial InjuryPIXIENCT02344797
Prevention of Myocardial Injury in Non-cardiac Surgery
A study testing Remote ischemic preconditioning in people with Myocardial Injury and Myocardial Infarction, run by Zealand University Hospital at 3 sites in Denmark.
Trial summary
Worldwide, more than 200 million patients have major non-cardiac surgery annually and a significant proportion of these patients suffer major cardiovascular complications (e.g. nonfatal myocardial infarction, cardiac arrest, vascular death) within 30 days of their surgery. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Myocardial Injury, Myocardial Infarction
- What is being tested?
- Remote ischemic preconditioning
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 573 participants
- Where
- 3 sitesDenmark
- Study dates
- 7 Feb 2015to 24 Aug 2018
- 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 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients ≥ 45 years undergoing in-hospital hip fracture surgery
- undergoing emergent or urgent surgery (i.e. emergent or urgent visitation to the Department of Orthopedic Surgery)
- fulfil 1 or more of the following 4 inclusion criteria, which are all determined during the conversation with the patient:
- Ischemic heart disease, defined by any of the following criteria A. angina pectoris B. prior myocardial infarction C. prior percutaneous coronary intervention D. prior coronary artery bypass graft
- Peripheral arterial disease, defined by any of the following criteria A. intermittent claudication B. reduced peripheral arterial blood flow C. prior vascular surgery due to peripheral arterial disease
- Prior stroke OR
- any 1 of 7 risk criteria A. age ≥70 years; B. congestive heart failure C. prior transient ischemic attack; D. diabetes and currently taking an oral hypoglycemic agent or insulin E. hypertension G. preoperative serum creatinine >175 µmol/L (>2.0 mg/dl) H. smoking within 2 years of surgery
Who cannot join
- History of peripheral arterial disease affecting both upper limbs
- Renal failure with eGRF<30ml/min/1.73m2
- Cardiogenic shock or cardiac arrest during the current hospital admission
- Reoperation after elective surgery carried out during the current hospital admission
- Not capable of giving informed consent after oral and written information
- Other conditions that prevent the performance of remote ischemic preconditioning.
- Previously included in this trial
Trial locations and contacts
3 sites in 1 country.
Denmark3 sites
Department of Anesthesia, Herlev Hospital
Herlev, Region H, 2730
Depertment of Orthopedic Surgery, Holstebro Hospital
Holstebro, Central Jutland, 7500
Department of Surgery, Koge Hospital
Køge, 4600
About this study
Official title: Prevention of Myocardial Injury by Remote Ischemic Preconditioning in Emergent or Urgent Non-cardiac Surgery: a Randomized Clinical Trial
Worldwide, more than 200 million patients have major non-cardiac surgery annually and a significant proportion of these patients suffer major cardiovascular complications (e.g. nonfatal myocardial infarction, cardiac arrest, vascular death) within 30 days of their surgery. Perioperative myocardial infarction is the most common cardiovascular complication and recent clinical studies have shown that even minor myocardial injury in relation to non-cardiac surgery is associated with 30-day mortality.
Remote ischemic preconditioning is a procedure, which protects remote tissues and organs e.g. against ischemia-reperfusion injury. Cycles of forearm or leg ischemia and reperfusion by the inflation of a blood-pressure cuff for brief periods are the preferred method.The aim of this interventional clinical study is to determine whether remote ischemic preconditioning can reduce markers of myocardial injury in emergent or urgent non-cardiac surgery.
Read the detailed description
Patients with a hip fracture will be included in the study. The patients will be randomized to remote ischemic preconditioning or control (no intervention). The remote ischemic preconditioning procedure is carried out immediately after the induction of regional or general anesthesia. The blood pressure cuff is placed on the upper limb. The cuff is inflated to 200 mmHg 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. The procedure is carried out 4 times in a row. For patients with systolic blood pressures >185 mmHg, the cuff will be inflated to at least 15 mmHg above the patient's systolic blood pressure.
The primary outcome is myocardial injury in noncardiac surgery within day 4 postoperatively.
We expect 15% of the patients in the placebo group to suffer myocardial injury while the incidence of myocardial injury is expected to be reduced to 7% in the intervention group. Type I error is set at 5% and type II error is set at 20%. In total 2 x 264 patients need to be included based on this power calculation. We will include patients until we have a total of 2 x 270 patients for evaluation (per-protocol).
- Conditions
- Myocardial Injury, Myocardial Infarction
- Being tested
- Remote ischemic preconditioning
- Keywords
- Perioperative, Postoperative Complications/prevention & control
- Medical subject headings
- Myocardial Infarction, Postoperative Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischemic preconditioningProcedure or surgery
The remote ischemic preconditioning procedure is carried out immediately after the induction of regional or general anesthesia. The blood pressure cuff is placed on the upper limb. The cuff is inflated to 200 mmHg 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. The procedure is carried out 4 times in a row. For patients with systolic blood pressures >185 mmHg, the cuff will be inflated to at least 15 mmHg above the patient's systolic blood pressure.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | Remote ischemic preconditioning, 4 cycles of 5 minutes ischemia and 5 minutes reperfusion of the forearm before surgery. Receives: Procedure: Remote ischemic preconditioning |
| Control | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with myocardial injury in non-cardiac surgery
Measured: during surgery or the first 4 days after surgery
Secondary outcomes (9)
Peak plasma TnI and total TnI release (area under the curve)
Measured: during surgery or the first 4 days after surgery
Endothelial dysfunction (reactive hyperemia index)
Assessed by EndoPat
Measured: 24 hours after surgery
Perioperative myocardial infarction
Measured: 30 days, one year and 5 years after surgery
Major adverse cardiovascular events
Measured: 30 days, one year and 5 years after surgery
Length of postoperative hospital stay
Measured: participants will be followed for the duration of hospital stay, an expected average of 10 days
Length of intensive care unit stay
Measured: participants will be followed for the duration of hospital stay, an expected average of 10 days
All-cause mortality
Measured: 30 days, one year and 5 years after surgery
Biomarkers of coagulation
Measured: preoperatively, 2 hours after incision, and on days 1 and 2 after surgery
Plasma N-terminal Pro-Brain Natriuretic Peptide
Plasma N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) before surgery and at day 1 after surgery.
Measured: Preoperative and day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2015 (estimated)
- Study start7 Feb 2015
- Primary completionSep 2017
- Study completion24 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Myocardial InjuryStudies 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
- Investigator, Outcomes assessor
- Enrolment
- 573 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sarah Victoria Ekeløf Busch, Zealand University Hospital
- Investigators
- Sarah E Busch, MD, Principal investigator, Department of Surgery, Koge Hospital, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02344797
- Sponsor's protocol ID
- SBpixie
- Acronym
- PIXIE
- Status last verified
- May 2019
- First submitted
- 13 Jan 2015
- Last updated
- 9 May 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Wahlstrom KL, Ekeloef S, Gogenur I, Munster AB. Myocardial injury after non-cardiac surgery and per operative fibrin metabolism in patients undergoing hip-fracture surgery: an observational study. Scand J Clin Lab Invest. 2023 Sep;83(5):299-308. doi: 10.1080/00365513.2023.2220970. Epub 2023 Aug 16.
PubMed 37584362Ekeloef S, Koyuncu S, Holst-Knudsen J, Gundel O, Meyhoff CS, Homilius M, Stilling M, Ekeloef P, Munster AMB, Mathiesen O, Gogenur I. Cardiovascular events in patients undergoing hip fracture surgery treated with remote ischaemic preconditioning: 1-year follow-up of a randomised clinical trial. Anaesthesia. 2021 Aug;76(8):1042-1050. doi: 10.1111/anae.15357. Epub 2021 Jan 13.
PubMed 33440017Ekeloef S, Homilius M, Stilling M, Ekeloef P, Koyuncu S, Munster AB, Meyhoff CS, Gundel O, Holst-Knudsen J, Mathiesen O, Gogenur I. The effect of remote ischaemic preconditioning on myocardial injury in emergency hip fracture surgery (PIXIE trial): phase II randomised clinical trial. BMJ. 2019 Dec 4;367:l6395. doi: 10.1136/bmj.l6395.
PubMed 31801725
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Myocardial Injury by Remote Ischemic Preconditioning in Emergent or Urgent Non-cardiac Surgery: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02344797
- Acronym / sponsor ID
- PIXIE / SBpixie
- Conditions
- Myocardial Injury, Myocardial Infarction
- Keywords
- Perioperative, Postoperative Complications/prevention & control
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 573 participants (actual)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Study start
- 7 Feb 2015
- Primary completion
- Sep 2017 (actual)
- Study completion
- 24 Aug 2018 (actual)
- First posted
- 26 Jan 2015 (estimated)
- 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.
Worldwide, more than 200 million patients have major non-cardiac surgery annually and a significant proportion of these patients suffer major cardiovascular complications (e.g. nonfatal myocardial infarction, cardiac arrest, vascular death) within 30 days of their surgery. Perioperative myocardial infarction is the most common cardiovascular complication and recent clinical studies have shown that even minor myocardial injury in relation to non-cardiac surgery is associated with 30-day mortality.
Remote ischemic preconditioning is a procedure, which protects remote tissues and organs e.g. against ischemia-reperfusion injury. Cycles of forearm or leg ischemia and reperfusion by the inflation of a blood-pressure cuff for brief periods are the preferred method.The aim of this interventional clinical study is to determine whether remote ischemic preconditioning can reduce markers of myocardial injury in emergent or urgent non-cardiac surgery.
Detailed description
Patients with a hip fracture will be included in the study. The patients will be randomized to remote ischemic preconditioning or control (no intervention). The remote ischemic preconditioning procedure is carried out immediately after the induction of regional or general anesthesia. The blood pressure cuff is placed on the upper limb. The cuff is inflated to 200 mmHg 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. The procedure is carried out 4 times in a row. For patients with systolic blood pressures >185 mmHg, the cuff will be inflated to at least 15 mmHg above the patient's systolic blood pressure.
The primary outcome is myocardial injury in noncardiac surgery within day 4 postoperatively.
We expect 15% of the patients in the placebo group to suffer myocardial injury while the incidence of myocardial injury is expected to be reduced to 7% in the intervention group. Type I error is set at 5% and type II error is set at 20%. In total 2 x 264 patients need to be included based on this power calculation. We will include patients until we have a total of 2 x 270 patients for evaluation (per-protocol).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Procedure: Remote ischemic preconditioningRemote ischemic preconditioning, 4 cycles of 5 minutes ischemia and 5 minutes reperfusion of the forearm before surgery. |
| Control | No intervention | – |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- patients ≥ 45 years undergoing in-hospital hip fracture surgery
- undergoing emergent or urgent surgery (i.e. emergent or urgent visitation to the Department of Orthopedic Surgery)
- fulfil 1 or more of the following 4 inclusion criteria, which are all determined during the conversation with the patient:
Key exclusion criteria (7 listed)
- History of peripheral arterial disease affecting both upper limbs
- Renal failure with eGRF<30ml/min/1.73m2
- Cardiogenic shock or cardiac arrest during the current hospital admission
- Reoperation after elective surgery carried out during the current hospital admission
- Not capable of giving informed consent after oral and written information
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 preconditioningThe remote ischemic preconditioning procedure is carried out immediately after the induction of regional or general anesthesia. The blood pressure cuff is placed on the upper limb. The cuff is inflated to 200 mmHg 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. The procedure is carried out 4 times in a row. For patients with systolic blood pressures >185 mmHg, the cuff will be inflated to at least 15 mmHg above the patient's systolic blood pressure. | Procedure or surgery | Intervention |
Primary outcome
Number of patients with myocardial injury in non-cardiac surgery
Time frame: during surgery or the first 4 days after surgery
9 secondary outcomes
Peak plasma TnI and total TnI release (area under the curve)
Time frame: during surgery or the first 4 days after surgery
Endothelial dysfunction (reactive hyperemia index)
Time frame: 24 hours after surgery
Perioperative myocardial infarction
Time frame: 30 days, one year and 5 years after surgery
Major adverse cardiovascular events
Time frame: 30 days, one year and 5 years after surgery
Length of postoperative hospital stay
Time frame: participants will be followed for the duration of hospital stay, an expected average of 10 days
Length of intensive care unit stay
Time frame: participants will be followed for the duration of hospital stay, an expected average of 10 days
All-cause mortality
Time frame: 30 days, one year and 5 years after surgery
Biomarkers of coagulation
Time frame: preoperatively, 2 hours after incision, and on days 1 and 2 after surgery
Plasma N-terminal Pro-Brain Natriuretic Peptide
Time frame: Preoperative and day 1
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 9 May 2019.
- Derived from this study: PubMed 37584362Wahlstrom KL, Ekeloef S, Gogenur I, Munster AB. Myocardial injury after non-cardiac surgery and per operative fibrin metabolism in patients undergoing hip-fracture surgery: an observational study. Scand J Clin Lab Invest. 2023 Sep;83(5):299-308. doi: 10.1080/00365513.2023.2220970. Epub 2023 Aug 16.
- Derived from this study: PubMed 33440017Ekeloef S, Koyuncu S, Holst-Knudsen J, Gundel O, Meyhoff CS, Homilius M, Stilling M, Ekeloef P, Munster AMB, Mathiesen O, Gogenur I. Cardiovascular events in patients undergoing hip fracture surgery treated with remote ischaemic preconditioning: 1-year follow-up of a randomised clinical trial. Anaesthesia. 2021 Aug;76(8):1042-1050. doi: 10.1111/anae.15357. Epub 2021 Jan 13.
- Derived from this study: PubMed 31801725Ekeloef S, Homilius M, Stilling M, Ekeloef P, Koyuncu S, Munster AB, Meyhoff CS, Gundel O, Holst-Knudsen J, Mathiesen O, Gogenur I. The effect of remote ischaemic preconditioning on myocardial injury in emergency hip fracture surgery (PIXIE trial): phase II randomised clinical trial. BMJ. 2019 Dec 4;367:l6395. doi: 10.1136/bmj.l6395.
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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.
Sarah E Busch, MD principal investigator
Department of Surgery, Koge Hospital, Denmark
3 sites 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 in people with Myocardial Injury and Myocardial Infarction, run by Zealand University Hospital at 3 sites 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 7 inclusion and 7 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 9 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Number of patients with myocardial injury in non-cardiac surgery (time frame: during surgery or the first 4 days 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 NCT02344797, which also lists 3 linked publications.
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 9 May 2019.