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Prevention of Myocardial Injury in Non-cardiac Surgery (PIXIE)

Primary Purpose

Myocardial Injury, Myocardial Infarction

Status

Completed

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

Remote ischemic preconditioning

About this trial

This is an interventional prevention trial for Myocardial Injury focused on measuring Perioperative, Postoperative Complications/prevention & control

Eligibility Criteria

45 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
1. 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
2. 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
3. Prior stroke OR
4. 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

Exclusion Criteria:

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

Sites / Locations

Department of Anesthesia, Herlev Hospital
Depertment of Orthopedic Surgery, Holstebro Hospital
Department of Surgery, Koge Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Intervention

Control

Arm Description

Remote ischemic preconditioning, 4 cycles of 5 minutes ischemia and 5 minutes reperfusion of the forearm before surgery.

Outcomes

Primary Outcome Measures

Number of patients with myocardial injury in non-cardiac surgery

Secondary Outcome Measures

Peak plasma TnI and total TnI release (area under the curve)

Endothelial dysfunction (reactive hyperemia index)

Assessed by EndoPat

Perioperative myocardial infarction

Major adverse cardiovascular events

Length of postoperative hospital stay

Length of intensive care unit stay

All-cause mortality

Biomarkers of coagulation

Plasma N-terminal Pro-Brain Natriuretic Peptide

Plasma N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) before surgery and at day 1 after surgery.

Full Information

NCT ID

NCT02344797

First Posted

January 13, 2015

Last Updated

May 7, 2019

Sponsor

Zealand University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02344797

Brief Title

Prevention of Myocardial Injury in Non-cardiac Surgery

Acronym

PIXIE

Official Title

Prevention of Myocardial Injury by Remote Ischemic Preconditioning in Emergent or Urgent Non-cardiac Surgery: a Randomized Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

February 7, 2015 (undefined)

Primary Completion Date

September 2017 (Actual)

Study Completion Date

August 24, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Zealand University Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myocardial Injury, Myocardial Infarction

Keywords

Perioperative, Postoperative Complications/prevention & control

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

InvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

573 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intervention

Arm Type

Active Comparator

Arm Description

Remote ischemic preconditioning, 4 cycles of 5 minutes ischemia and 5 minutes reperfusion of the forearm before surgery.

Arm Title

Control

Arm Type

No Intervention

Intervention Type

Procedure

Intervention Name(s)

Remote ischemic preconditioning

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of patients with myocardial injury in non-cardiac surgery

Time Frame

during surgery or the first 4 days after surgery

Secondary Outcome Measure Information:

Title

Peak plasma TnI and total TnI release (area under the curve)

Time Frame

during surgery or the first 4 days after surgery

Title

Endothelial dysfunction (reactive hyperemia index)

Description

Assessed by EndoPat

Time Frame

24 hours after surgery

Title

Perioperative myocardial infarction

Time Frame

30 days, one year and 5 years after surgery

Title

Major adverse cardiovascular events

Time Frame

30 days, one year and 5 years after surgery

Title

Length of postoperative hospital stay

Time Frame

participants will be followed for the duration of hospital stay, an expected average of 10 days

Title

Length of intensive care unit stay

Time Frame

participants will be followed for the duration of hospital stay, an expected average of 10 days

Title

All-cause mortality

Time Frame

30 days, one year and 5 years after surgery

Title

Biomarkers of coagulation

Time Frame

preoperatively, 2 hours after incision, and on days 1 and 2 after surgery

Title

Plasma N-terminal Pro-Brain Natriuretic Peptide

Description

Plasma N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) before surgery and at day 1 after surgery.

Time Frame

Preoperative and day 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sarah E Busch, MD

Organizational Affiliation

Department of Surgery, Koge Hospital, Denmark

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Anesthesia, Herlev Hospital

City

Herlev

State/Province

Region H

ZIP/Postal Code

2730

Country

Denmark

Facility Name

Depertment of Orthopedic Surgery, Holstebro Hospital

City

Holstebro

State/Province

Region Midtjylland

ZIP/Postal Code

7500

Country

Denmark

Facility Name

Department of Surgery, Koge Hospital

City

Køge

ZIP/Postal Code

4600

Country

Denmark

12. IPD Sharing Statement

Citations:

PubMed Identifier

33440017

Citation

Ekeloef 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.

Results Reference

derived

PubMed Identifier

31801725

Citation

Ekeloef 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.

Results Reference

derived

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Prevention of Myocardial Injury in Non-cardiac Surgery

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